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Actualité pharmacieutique

Une mini revue sur le système d'administration de médicaments par nanosuspension: une approche innovante pour les médicaments peu solubles dans l'eau

Cours Pharma

Admission pharmaceutique

cours de pharmacie

admission pharmaceutique

À propos des auteurs
Praveen Kumar. K * 1, Sudhir KK1, Akshay KA1, Sachin KK1, Shripathy. D2, Shabaraya AR3.
1M Pharm, Département de pharmacie, Collège de pharmacie de Srinivas, Mangalore- 574143)
2Professeur associé, Département de Pharmaceutique, Collège de Pharmacie de Srinivas)
3Directeur et chef de la pharmacie, Collège de pharmacie de Srinivas, Mangalore)
* kodavanjipraveen@gmail.com

ABSTRAIT
Les nanosuspensions pharmaceutiques sont une technique émergente permettant aux médicaments insolubles de les rendre aussi solubles. Plus de 40% des nouveaux médicaments sont produits dans le cadre de programmes de découverte de médicaments sont des composés peu solubles dans l'eau. La formulation d'un médicament peu soluble dans l'eau a toujours été un problème difficile pour l'industrie pharmaceutique. Les techniques comme les méthodes ascendantes et descendantes. Les solvants, les stabilisants et les conservateurs sont très essentiels pour la formulation des nanosuspensions. La taille des particules dans la plage de 100 à 600 nm, le pourcentage d'efficacité d'encapsulation du médicament (% EE) et le potentiel zêta dans la plage de -25 à + 25 mV. Les autres paramètres d'évaluation comme l'étude de diffraction des rayons X, la libération cinétique, ont également été effectués en fonction du type de formulations.

INTRODUCTION
En général, l'ingrédient pharmaceutique actif est très important dans la préparation de formulations pharmaceutiques. Mais plus de 40% des ingrédients pharmaceutiques actifs sont synthétisés dans le cadre de programmes de découverte de médicaments insolubles dans l'eau ou lipophiles. La formulation d'une forme soluble faiblement aqueuse peut être convertie en une forme soluble est un problème difficile pour le scientifique pharmaceutique. La formulation innovante contenant des particules de taille nanométrique peut être fabriquée pour tous les composés médicamenteux appartenant aux classes BCS II et IV. Pour améliorer leur solubilité et donc la pénétration du médicament de l'intestin à la circulation systémique par la barrière gastro-intestinale.1
Fondamentalement, l'étape limitant la vitesse d'absorption des médicaments dans les classes ci-dessus est la vitesse de dissolution résultant d'une faible solubilité. Bien que les médicaments aient une perméabilité élevée, la faible solubilité entraîne un faible gradient de concentration entre l'intestin et le vaisseau sanguin résultant d'un problème de transport de médicament et d'absorption orale. Aujourd'hui, un grand pourcentage de composés médicamenteux dans le développement de médicaments représente une mauvaise solubilité aqueuse. Par conséquent, l'une des tâches les plus difficiles du développement de médicaments est d'améliorer la solubilité des médicaments afin d'améliorer la biodisponibilité de ces médicaments.2

Il existe de nombreux procédés existants pour améliorer la solubilité de médicaments faiblement aqueux, qui comprennent la micronisation, la co-solvabilité, la forme de sel, l'utilisation de tensioactifs, la technique de précipitation. D'autres techniques telles que les liposomes, les émulsions, la micro-émulsion, la dispersion solide et le complexe d'inclusion de cyclodextrine peuvent améliorer considérablement la solubilité du médicament, mais elles ne sont pas possibles pour tous les médicaments. Cependant, ces méthodes ont leurs propres inconvénients tels qu'une grande quantité d'additifs qui peuvent induire des problèmes de stabilité et de toxicité. Par conséquent, ils ne sont souvent pas idéaux pour le traitement clinique.3 depuis que le système d'administration de médicaments par nanosuspension a été développé pour la première fois en 1994, et la nanosuspension a attiré plus d'attention en tant que formulation pour les médicaments solubles faiblement aqueux.4

La nanosuspension développée sur le plan pharmaceutique peut être définie comme des particules de médicament très finement colloïdales ou biphasiques, dispersées ou solides sous forme posologique de véhicule aqueux, granulométrie de moins de 1 µm, sans aucun matériau de matrice, stabilisée en utilisant des agents tensioactifs et des stabilisants appropriés, préparés par des des méthodes pour les applications de délivrance de médicaments basées sur le site d'application telles que les voies orale, topique, parentérale, oculaire et pulmonaire. Ce type de formulations résout non seulement le problème de la faible solubilité aqueuse et de la disponibilité des médicaments dans le corps et modifie également la pharmacocinétique du médicament et qui améliore la sécurité et l'efficacité. Cette approche avancée est la plus appropriée pour les composés avec une valeur log P plus élevée, un point de fusion élevé et une dose initiale plus élevée. Plus de disponibilité des médicaments dans le corps par rapport aux méthodes existantes d'administration de médicaments. La diminution de la taille des particules conduit à une augmentation de la surface spécifique et une augmentation absolue de la vitesse de dissolution comme décrit par la modification de Nernst-Brunner & Levich ou l'équation de Noyes-Whitney. De plus, une légère augmentation de la solubilité à saturation dépend de la réduction de la taille des particules due à une augmentation de la pression de dissolution. Cela peut être expliqué par l'équation d'Ostwald-Freundlich. Selon la technique de production appliquée, des modifications de la structure cristalline des particules de médicament peuvent également se produire. Une quantité croissante de fraction médicamenteuse amorphe pourrait produire une solubilité de saturation plus élevée. De plus, une adhésivité générale au tissu a été décrite pour les nanoparticules.

Ces types d'innovations, le médicament doit être maintenu à l'état cristallin avec une taille de particule réduite, conduisant à une augmentation de la vitesse de dissolution et donc une biodisponibilité améliorée. La forme encapsulée de médicament dans la nanosuspension peut exister dans un état cristallin ou amorphe pharmaceutiquement accepté. Dans cette nouvelle technique, il est possible de formuler avec succès les molécules de poussière de brique pour une meilleure dissolution et une bonne absorption.

Critères de sélection de la molécule hôte en tant que nanosuspension: 7
Dans cette méthode, l'API qui présente l'une des caractéristiques suivantes telles que,
a) Molécule médicamenteuse non aqueuse ayant une bonne solubilité dans les huiles.
b) L'ingrédient pharmaceutique actif non aqueux est insoluble dans l'eau et les huiles.
c) Molécules médicamenteuses ayant la tendance des petits cristaux à dissoudre le solvant.
d) Grandes molécules de dose initiale.

Avantages: 8
1. Les nanosuspensions étaient plus stables que les porteurs lipoïdaux.
2. Fournir une facilité de fabrication et une mise à l'échelle pour la production à grande échelle.
3. Les désagréments tissulaires peuvent être réduits en les formulant sous forme de nanosuspension.
4. Biodisponibilité améliorée par voie oculaire et par inhalation.
5. La voie parentérale (IV) peut être réalisée rapidement. & ciblage tissulaire.
6. Forme posologique solide contenant une nanosuspension pour produire une biodisponibilité améliorée.
7. La durée d'action peut être augmentée en raison du niveau submicronique de la taille des particules.
8. Un médicament avec une valeur de pénétrabilité plus élevée peut être formulé sous forme de nanosuspension pour augmenter la biodisponibilité ainsi que la durée d'action.
9. Une vitesse de dissolution élevée peut être obtenue en raison de l'amélioration des performances tissulaires et de la solubilité à saturation des molécules de médicament.
10. Il peut être converti en des formes posologiques appropriées telles que des comprimés, des capsules, des pastilles, de l'hydrogel et des suppositoires en fonction de l'exigence du formulateur.
11. La fraction amorphe des particules augmente conduisant à une charge de surface dans la structure cristalline conduit à une solubilité plus élevée.
12. La modification de surface de la nanosuspension est l'une des possibilités de cibler un site spécifique.

Inconvénients du système d'administration de médicaments Nanosuspension:
1. L'instabilité physique est l'un des principaux inconvénients de ce type de formulation.
2. Le soin doit être pris lors de la manipulation et du transport, car la préparation peut être en vrac.
3. La fixation de la dose peut être difficile.

Méthodes de préparation de la nanosuspension: 9, 11, 16, 24, 26, 27
Les techniques de préparation de nanosuspension peuvent être globalement classées en quatre méthodes telles que,
I. Techniques ascendantes
II. Techniques de haut en bas
III. Techniques combinées
IV. Autres techniques

Fig no: 01 Méthodes de préparation des nanosuspensions

I Technologie ascendante:
C'est la méthode la plus ancienne. Dans ce procédé, le médicament ou la molécule hôte peut être dissous dans le solvant organique et pourrait être injecté à travers le solvant aqueux. La solution entière peut être stabilisée par des stabilisants appropriés.
Avantage :
1) Utilisation des méthodes les plus simples et courantes.
2) Une solubilité à saturation plus élevée est l'un des avantages de la précipitation par rapport à une autre méthode de préparation.

Désavantages :
1) La solubilité des médicaments est le critère principal.
2) La miscibilité du solvant avec au moins un non-solvant doit être requise.
3) L'élimination complète des résidus de solvants est une autre étape difficile, augmentant ainsi les coûts de production.
4) La préservation du caractère des particules est un peu difficile (c'est-à-dire la taille, en cas de fraction amorphe). Cela peut être fait en utilisant un sécheur par atomisation comme processus de deuxième étape pour la préservation de la taille des particules.

Par exemple: méthode d'ultrasonication des précipitations

Fig no: 02 Méthodes d'ultrasonication des précipitations

II Technologie Top-Down:
Les technologies descendantes comprennent,
a) Méthode de fraisage des supports:

Fig no: 03 Méthode de fraisage du support

b) Méthode d'homogénéisation haute pression:

Fig no: 04 Homogénéisation haute pression (HPH)

III Méthodes de combinaison:

1.0 Méthode de diffusion d'émulsion:

Fig no: 05 Méthode de diffusion d'émulsion

2.0 Modèle de micro-émulsion;

Fig no: 06 Méthode de modèle de micro-émulsion

IV Méthodes plus récentes:
je. Méthode du fluide supercritique;
La technologie des fluides supercritiques est la méthode avancée pour préparer des nanoparticules à partir de solutions médicamenteuses. L'expansion rapide du processus de solution supercritique (RESS). Il implique le passage d'un fluide supercritique contenant des médicaments à travers une buse, ce qui conduit à la précipitation des particules fines de taille nanométrique par évaporation de solvants.

Fig no: 07 Méthode des fluides super critiques

ii Co-broyage à sec;
Ce sont les techniques modifiées de la méthode de fraisage conventionnelle. Cette méthode est applicable dans le cas de médicaments peu solubles avec des polymères solubles et les copolymères peuvent être dispersés dans un liquide ou un milieu approprié. Des polymères comme le PVP, le polyéthylène glycol (PEG), l'hydroxypropyl méthylcellulose (HPMC) et les dérivés de cyclodextrine ont été utilisés dans la préparation de nanosuspensions.

Composants de la formulation de nanosuspension: La formulation de nanosuspension nécessite essentiellement un stabilisant ou un surfactant, un système de solvant approprié et d'autres ingrédients pour sa préparation7.

Tableau n °: 01 Ingrédients requis pour la formulation de nanosuspension

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SL NO:

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Ingrédients

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Rôle des ingrédients dans la formulation

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Exemples

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01

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Stabilisateurs

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Il peut être utilisé pour réduire l'énergie libre de surface ou l'agrégation ou la tension de surface qui peuvent être essentielles pour la stabilité physique de la nanosuspension pharmaceutique.

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Polysorbates, povidone, poloxamère et lécithine

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02

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Solvants

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Les solvants organiques sont plus courants, mais ils sont moins dangereux par nature.

Doit solubiliser l'ingrédient pharmaceutique actif.

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Méthanol, éthanol, DMSO, chloroforme.

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03

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Conservateurs

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L'ensemble de la formulation peut être protégé de l'attaque microbienne.

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Acide benzoïque, méthyl ou propyl parabens.

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04

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Co-tensioactifs

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Ils sont le comportement de phase d'influence. Par conséquent, l'effet du co-surfactant sur l'absorption de la phase interne ou la charge médicamenteuse doit être étudié.

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Transcutol, sels biliaires, isopropanol.

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05

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Autres additifs

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Les utilisations d'autres ingrédients dépendent principalement de la voie d'administration ou des propriétés physico-chimiques du médicament.

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Tampons, sels, polyols, osmogènes et cryoprotecteur

Caractérisation des formulations de nanosuspension:
Les nanosuspensions sont caractérisées pour leur apparence physique, les interactions avec les excipients médicamenteux étudiées par FTIR, la taille des particules, le potentiel zêta, l'état cristallin, les études de dissolution et les études in vivo. Parmi celles-ci, les techniques de caractérisation les plus importantes ont été discutées.

Etudes de pré formulation:
• Les propriétés physico-chimiques du médicament et des excipients peuvent être évaluées. Études de pré-formulation comme la couleur, la détermination du point de fusion, les études de solubilité dans différents solvants, l'étude FTIR.
• Détermination du point de fusion:
Le point de fusion peut être déterminé par la méthode capillaire. L'échantillon a été inséré dans un tube capillaire ayant une extrémité fermée. Ensuite, le capillaire a été inséré dans le tube de Thiele qui a été chauffé de manière contrôlée. La température à laquelle l'échantillon de médicament a commencé à fondre a été notée comme température de point de fusion.
• Etudes de solubilité:
La solubilité est basée sur le type de médicament utilisé dans la préparation. Les nanosuspensions présentent un avantage important par rapport aux autres techniques, car elles peuvent augmenter la vitesse de dissolution ainsi que la solubilité à saturation. La solubilité à saturation du médicament dans différents tampons physiologiques ainsi qu'à différentes températures doit être évaluée à l'aide des méthodes décrites dans la littérature.

Etude post formulation:
1. Détermination de la viscosité:
Il peut être étudié en utilisant un viscosimètre rotatif Brookfield à température ambiante

2. Analyse granulométrique et potentiel zêta:
Il peut être étudié en utilisant le calibreur zêta Malvern. Ce paramètre est très important. La plage de taille moyenne des particules est de 200 à 600 nm

3. Pourcentage d'efficacité de piégeage du médicament:
Le méthanol est utilisé comme solvant standard utilisé pour briser les nanoparticules, après centrifugation pour obtenir le médicament piégé et libre. Retirez le médicament non emballé / libre. Le% EE est calculé en utilisant la formule,
% D'efficacité du piégeage = Médicament ajouté – Médicament gratuit / Total du médicament * 100

4. Etude de diffraction des rayons X:
Il est utilisé pour étudier la nature des cristaux de nanoparticules

5. Libération de médicament in vitro:
La nanosuspension est placée sur un côté de la membrane de cellophane dans une cellule de diffusion Franz verticale. L'autre face de la membrane était en contact avec le milieu de dissolution. L'ensemble de dissolution entier a été placé sur un agitateur magnétique à une température de 37 ° C. Le milieu de dissolution a été prélevé à différents intervalles de temps – 1 h, 2 h, 3 h, 4 h, 5 h, 6 h,. Chaque fois que l'échantillon a été prélevé, un volume égal de milieu de dissolution frais a été ajouté à la cellule pour maintenir un volume constant. Les concentrations de médicament dans le milieu de dissolution ont été déterminées par la méthode spectrophotométrique UV

6. Stabilité de la nanosuspension:
L'énergie de surface élevée des particules nanométriques induit une agglomération des cristaux de médicament. La fonction principale du stabilisant est de mouiller complètement les particules de médicament pour empêcher la maturation d'Ostwald et l'agglomération de la nanosuspension et de former une formulation physiquement stable en fournissant une barrière stérique ou ionique.
Les paramètres d'évaluation peuvent être modifiés en fonction du type de formulations.

Application thérapeutique des nanosuspensions

Tableau n °: 02 Applications de la nanosuspension

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background1; mso-border-themeshade: 191; padding: 0in 5.4pt 0in 5.4pt "valign =" top "width =" 65 "> <p class =" MsoListParagraphCxSpFirst "style =" margin: 0in; margin-bottom: .0001pt ;

mso-add-space: auto; text-align: justify; line-height: normal ">01

<td style = "width: 80.15pt; border-top: none; border-left:

aucun; border-bottom: solid #BFBFBF 1.0pt; mso-border-bottom-themecolor: background1;

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background1; mso-border-right-themeshade: 191; mso-border-top-alt: solid #BFBFBF .5pt;

mso-border-top-themecolor: background1; mso-border-top-themeshade: 191;

mso-border-left-alt: solid #BFBFBF .5pt; mso-border-left-themecolor: background1;

mso-border-left-themeshade: 191; mso-border-alt: solid #BFBFBF .5pt; mso-border-themecolor:

background1; mso-border-themeshade: 191; padding: 0in 5.4pt 0in 5.4pt "valign =" top "width =" 107 "> <p class =" MsoListParagraphCxSpMiddle "style =" margin: 0in; margin-bottom: .0001pt ;

mso-add-space: auto; text-align: justify; line-height: normal ">Oral

<td style = "width: 90,55pt; border-top: none; border-left:

aucun; border-bottom: solid #BFBFBF 1.0pt; mso-border-bottom-themecolor: background1;

mso-border-bottom-themeshade: 191; border-right: solid #BFBFBF 1.0pt; mso-border-right-themecolor:

background1; mso-border-right-themeshade: 191; mso-border-top-alt: solid #BFBFBF .5pt;

mso-border-top-themecolor: background1; mso-border-top-themeshade: 191;

mso-border-left-alt: solid #BFBFBF .5pt; mso-border-left-themecolor: background1;

mso-border-left-themeshade: 191; mso-border-alt: solid #BFBFBF .5pt; mso-border-themecolor:

background1; mso-border-themeshade: 191; padding: 0in 5.4pt 0in 5.4pt "valign =" top "width =" 121 "> <p class =" MsoListParagraphCxSpMiddle "style =" margin: 0in; margin-bottom: .0001pt ;

mso-add-space: auto; text-align: justify; line-height: normal ">Atovaquone, Bupravaquone, AINS.

<td style = "width: 203,3pt; border-top: none; border-left:

aucun; border-bottom: solid #BFBFBF 1.0pt; mso-border-bottom-themecolor: background1;

mso-border-bottom-themeshade: 191; border-right: solid #BFBFBF 1.0pt; mso-border-right-themecolor:

background1; mso-border-right-themeshade: 191; mso-border-top-alt: solid #BFBFBF .5pt;

mso-border-top-themecolor: background1; mso-border-top-themeshade: 191;

mso-border-left-alt: solid #BFBFBF .5pt; mso-border-left-themecolor: background1;

mso-border-left-themeshade: 191; mso-border-alt: solid #BFBFBF .5pt; mso-border-themecolor:

background1; mso-border-themeshade: 191; padding: 0in 5.4pt 0in 5.4pt "valign =" top "width =" 271 "> <p class =" MsoListParagraphCxSpMiddle "style =" margin-bottom: 0in; margin-bottom:

.0001pt; mso-add-space: auto; text-align: justify; text-indent: -. 25in; line-height:

normal; liste-mso: l2 niveau1 lfo1 ">· Amélioration de la biodisponibilité et de la solubilité par voie orale en cas de médicaments insolubles.

<p class = "MsoListParagraphCxSpMiddle" style = "margin-bottom: 0in; margin-bottom:

.0001pt; mso-add-space: auto; text-align: justify; text-indent: -. 25in; line-height:

normal; liste-mso: l2 niveau1 lfo1 ">· Réduisez la fréquence de dosage.

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.0001pt; mso-add-space: auto; text-align: justify; text-indent: -. 25in; line-height:

normal; liste-mso: l2 niveau1 lfo1 ">· Une grande surface permet d'améliorer le début de l'action.

<p class = "MsoListParagraphCxSpLast" style = "margin-bottom: 0in; margin-bottom:

.0001pt; mso-add-space: auto; text-align: justify; text-indent: -. 25in; line-height:

normal; liste-mso: l2 niveau1 lfo1 ">· Minimisez la concentration plasmatique maximale (Cmax) en cas de médicaments irritants.

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mso-border-top-themeshade: 191; mso-border-alt: solid #BFBFBF .5pt; mso-border-themecolor:

background1; mso-border-themeshade: 191; padding: 0in 5.4pt 0in 5.4pt "valign =" top "width =" 65 "> <p class =" MsoListParagraphCxSpFirst "style =" margin: 0in; margin-bottom: .0001pt ;

mso-add-space: auto; text-align: justify; line-height: normal ">02

<td style = "width: 80.15pt; border-top: none; border-left:

aucun; border-bottom: solid #BFBFBF 1.0pt; mso-border-bottom-themecolor: background1;

mso-border-bottom-themeshade: 191; border-right: solid #BFBFBF 1.0pt; mso-border-right-themecolor:

background1; mso-border-right-themeshade: 191; mso-border-top-alt: solid #BFBFBF .5pt;

mso-border-top-themecolor: background1; mso-border-top-themeshade: 191;

mso-border-left-alt: solid #BFBFBF .5pt; mso-border-left-themecolor: background1;

mso-border-left-themeshade: 191; mso-border-alt: solid #BFBFBF .5pt; mso-border-themecolor:

background1; mso-border-themeshade: 191; padding: 0in 5.4pt 0in 5.4pt "valign =" top "width =" 107 "> <p class =" MsoListParagraphCxSpMiddle "style =" margin: 0in; margin-bottom: .0001pt ;

mso-add-space: auto; text-align: justify; line-height: normal ">Parentéral

<td style = "width: 90,55pt; border-top: none; border-left:

aucun; border-bottom: solid #BFBFBF 1.0pt; mso-border-bottom-themecolor: background1;

mso-border-bottom-themeshade: 191; border-right: solid #BFBFBF 1.0pt; mso-border-right-themecolor:

background1; mso-border-right-themeshade: 191; mso-border-top-alt: solid #BFBFBF .5pt;

mso-border-top-themecolor: background1; mso-border-top-themeshade: 191;

mso-border-left-alt: solid #BFBFBF .5pt; mso-border-left-themecolor: background1;

mso-border-left-themeshade: 191; mso-border-alt: solid #BFBFBF .5pt; mso-border-themecolor:

background1; mso-border-themeshade: 191; padding: 0in 5.4pt 0in 5.4pt "valign =" top "width =" 121 "> <p class =" MsoListParagraphCxSpMiddle "style =" margin: 0in; margin-bottom: .0001pt ;

mso-add-space: auto; text-align: justify; line-height: normal ">Anti-cancers

<td style = "width: 203,3pt; border-top: none; border-left:

aucun; border-bottom: solid #BFBFBF 1.0pt; mso-border-bottom-themecolor: background1;

mso-border-bottom-themeshade: 191; border-right: solid #BFBFBF 1.0pt; mso-border-right-themecolor:

background1; mso-border-right-themeshade: 191; mso-border-top-alt: solid #BFBFBF .5pt;

mso-border-top-themecolor: background1; mso-border-top-themeshade: 191;

mso-border-left-alt: solid #BFBFBF .5pt; mso-border-left-themecolor: background1;

mso-border-left-themeshade: 191; mso-border-alt: solid #BFBFBF .5pt; mso-border-themecolor:

background1; mso-border-themeshade: 191; padding: 0in 5.4pt 0in 5.4pt "valign =" top "width =" 271 "> <p class =" MsoListParagraphCxSpMiddle "style =" margin-bottom: 0in; margin-bottom:

.0001pt; mso-add-space: auto; text-align: justify; text-indent: -. 25in; line-height:

normal; liste-mso: l3 niveau1 lfo2 ">· Réduisez la toxicité.

<p class = "MsoListParagraphCxSpMiddle" style = "margin-bottom: 0in; margin-bottom:

.0001pt; mso-add-space: auto; text-align: justify; text-indent: -. 25in; line-height:

normal; liste-mso: l3 niveau1 lfo2 ">· Améliorer la perméabilité

<p class = "MsoListParagraphCxSpLast" style = "margin-bottom: 0in; margin-bottom:

.0001pt; mso-add-space: auto; text-align: justify; text-indent: -. 25in; line-height:

normal; liste-mso: l3 niveau1 lfo2 ">· La taille des particules de 100 à 300 nm peut cibler efficacement les cellules tumorales.

<td style = "largeur: 48,8pt; bordure: solide #BFBFBF 1.0pt;

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mso-border-top-themeshade: 191; mso-border-alt: solid #BFBFBF .5pt; mso-border-themecolor:

background1; mso-border-themeshade: 191; padding: 0in 5.4pt 0in 5.4pt "valign =" top "width =" 65 "> <p class =" MsoListParagraphCxSpFirst "style =" margin: 0in; margin-bottom: .0001pt ;

mso-add-space: auto; text-align: justify; line-height: normal ">03

<td style = "width: 80.15pt; border-top: none; border-left:

aucun; border-bottom: solid #BFBFBF 1.0pt; mso-border-bottom-themecolor: background1;

mso-border-bottom-themeshade: 191; border-right: solid #BFBFBF 1.0pt; mso-border-right-themecolor:

background1; mso-border-right-themeshade: 191; mso-border-top-alt: solid #BFBFBF .5pt;

mso-border-top-themecolor: background1; mso-border-top-themeshade: 191;

mso-border-left-alt: solid #BFBFBF .5pt; mso-border-left-themecolor: background1;

mso-border-left-themeshade: 191; mso-border-alt: solid #BFBFBF .5pt; mso-border-themecolor:

background1; mso-border-themeshade: 191; padding: 0in 5.4pt 0in 5.4pt "valign =" top "width =" 107 "> <p class =" MsoListParagraphCxSpMiddle "style =" margin: 0in; margin-bottom: .0001pt ;

mso-add-space: auto; text-align: justify; line-height: normal ">Dermique

<td style = "width: 90,55pt; border-top: none; border-left:

aucun; border-bottom: solid #BFBFBF 1.0pt; mso-border-bottom-themecolor: background1;

mso-border-bottom-themeshade: 191; border-right: solid #BFBFBF 1.0pt; mso-border-right-themecolor:

background1; mso-border-right-themeshade: 191; mso-border-top-alt: solid #BFBFBF .5pt;

mso-border-top-themecolor: background1; mso-border-top-themeshade: 191;

mso-border-left-alt: solid #BFBFBF .5pt; mso-border-left-themecolor: background1;

mso-border-left-themeshade: 191; mso-border-alt: solid #BFBFBF .5pt; mso-border-themecolor:

background1; mso-border-themeshade: 191; padding: 0in 5.4pt 0in 5.4pt "valign =" top "width =" 121 "> <p class =" MsoListParagraphCxSpMiddle "style =" margin: 0in; margin-bottom: .0001pt ;

mso-add-space: auto; text-align: justify; line-height: normal ">Anti-oxydants comme le resvératrol

<td style = "width: 203,3pt; border-top: none; border-left:

aucun; border-bottom: solid #BFBFBF 1.0pt; mso-border-bottom-themecolor: background1;

mso-border-bottom-themeshade: 191; border-right: solid #BFBFBF 1.0pt; mso-border-right-themecolor:

background1; mso-border-right-themeshade: 191; mso-border-top-alt: solid #BFBFBF .5pt;

mso-border-top-themecolor: background1; mso-border-top-themeshade: 191;

mso-border-left-alt: solid #BFBFBF .5pt; mso-border-left-themecolor: background1;

mso-border-left-themeshade: 191; mso-border-alt: solid #BFBFBF .5pt; mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt" valign="top" width="271"><p class="MsoListParagraphCxSpLast" style="margin-bottom:0in;margin-bottom:

.0001pt;mso-add-space:auto;text-align:justify;text-indent:-.25in;line-height:

normal;mso-list:l1 level1 lfo3">· Increasing the physical stability.

<td style="width:48.8pt;border:solid #BFBFBF 1.0pt;

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mso-border-top-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt" valign="top" width="65"><p class="MsoListParagraphCxSpFirst" style="margin:0in;margin-bottom:.0001pt;

mso-add-space:auto;text-align:justify;line-height:normal">04

<td style="width:80.15pt;border-top:none;border-left:

none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:background1;

mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;mso-border-right-themecolor:

background1;mso-border-right-themeshade:191;mso-border-top-alt:solid #BFBFBF .5pt;

mso-border-top-themecolor:background1;mso-border-top-themeshade:191;

mso-border-left-alt:solid #BFBFBF .5pt;mso-border-left-themecolor:background1;

mso-border-left-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt" valign="top" width="107"><p class="MsoListParagraphCxSpMiddle" style="margin:0in;margin-bottom:.0001pt;

mso-add-space:auto;text-align:justify;line-height:normal">Ocular

<td style="width:90.55pt;border-top:none;border-left:

none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:background1;

mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;mso-border-right-themecolor:

background1;mso-border-right-themeshade:191;mso-border-top-alt:solid #BFBFBF .5pt;

mso-border-top-themecolor:background1;mso-border-top-themeshade:191;

mso-border-left-alt:solid #BFBFBF .5pt;mso-border-left-themecolor:background1;

mso-border-left-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt" valign="top" width="121"><p class="MsoListParagraphCxSpMiddle" style="margin:0in;margin-bottom:.0001pt;

mso-add-space:auto;text-align:justify;line-height:normal">Flurbiprofen and Ibuprofen

<td style="width:203.3pt;border-top:none;border-left:

none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:background1;

mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;mso-border-right-themecolor:

background1;mso-border-right-themeshade:191;mso-border-top-alt:solid #BFBFBF .5pt;

mso-border-top-themecolor:background1;mso-border-top-themeshade:191;

mso-border-left-alt:solid #BFBFBF .5pt;mso-border-left-themecolor:background1;

mso-border-left-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt" valign="top" width="271"><p class="MsoListParagraphCxSpMiddle" style="margin-bottom:0in;margin-bottom:

.0001pt;mso-add-space:auto;text-align:justify;text-indent:-.25in;line-height:

normal;mso-list:l1 level1 lfo3">· Rapid dissolution and bioavailability.

<p class="MsoListParagraphCxSpMiddle" style="margin-bottom:0in;margin-bottom:

.0001pt;mso-add-space:auto;text-align:justify;text-indent:-.25in;line-height:

normal;mso-list:l1 level1 lfo3">· Sustained release if the proper surface modification can be done by using suitable bio adhesive hydrophilic polymer.

<p class="MsoListParagraphCxSpLast" style="margin-bottom:0in;margin-bottom:

.0001pt;mso-add-space:auto;text-align:justify;text-indent:-.25in;line-height:

normal;mso-list:l1 level1 lfo3">· Eye irritation and blurred vision can be reduced

<td style="width:48.8pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-top:none;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt" valign="top" width="65"><p class="MsoListParagraphCxSpFirst" style="margin:0in;margin-bottom:.0001pt;

mso-add-space:auto;text-align:justify;line-height:normal">05

<td style="width:80.15pt;border-top:none;border-left:

none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:background1;

mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;mso-border-right-themecolor:

background1;mso-border-right-themeshade:191;mso-border-top-alt:solid #BFBFBF .5pt;

mso-border-top-themecolor:background1;mso-border-top-themeshade:191;

mso-border-left-alt:solid #BFBFBF .5pt;mso-border-left-themecolor:background1;

mso-border-left-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt" valign="top" width="107"><p class="MsoListParagraphCxSpMiddle" style="margin:0in;margin-bottom:.0001pt;

mso-add-space:auto;text-align:justify;line-height:normal">Pulmonary

<td style="width:90.55pt;border-top:none;border-left:

none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:background1;

mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;mso-border-right-themecolor:

background1;mso-border-right-themeshade:191;mso-border-top-alt:solid #BFBFBF .5pt;

mso-border-top-themecolor:background1;mso-border-top-themeshade:191;

mso-border-left-alt:solid #BFBFBF .5pt;mso-border-left-themecolor:background1;

mso-border-left-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt" valign="top" width="121"><p class="MsoListParagraphCxSpMiddle" style="margin:0in;margin-bottom:.0001pt;

mso-add-space:auto;text-align:justify;line-height:normal">Corticosteroids, Antiasthmatic agents

<td style="width:203.3pt;border-top:none;border-left:

none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:background1;

mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;mso-border-right-themecolor:

background1;mso-border-right-themeshade:191;mso-border-top-alt:solid #BFBFBF .5pt;

mso-border-top-themecolor:background1;mso-border-top-themeshade:191;

mso-border-left-alt:solid #BFBFBF .5pt;mso-border-left-themecolor:background1;

mso-border-left-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt" valign="top" width="271"><p class="MsoListParagraphCxSpMiddle" style="margin-bottom:0in;margin-bottom:

.0001pt;mso-add-space:auto;text-align:justify;text-indent:-.25in;line-height:

normal;mso-list:l0 level1 lfo4;mso-layout-grid-align:none;text-autospace:

none">· An aqueous nebulizer, could achieve pulmonary drug administration by producing a suitable droplet size.

<p class="MsoListParagraphCxSpMiddle" style="margin-bottom:0in;margin-bottom:

.0001pt;mso-add-space:auto;text-align:justify;text-indent:-.25in;line-height:

normal;mso-list:l0 level1 lfo4;mso-layout-grid-align:none;text-autospace:

none">· It is easy to achieve the droplet size in range of 01-05 can spread them rapidly on the lung surface to enable better absorption.

<p class="MsoListParagraphCxSpLast" style="margin-bottom:0in;margin-bottom:

.0001pt;mso-add-space:auto;text-align:justify;text-indent:-.25in;line-height:

normal;mso-list:l0 level1 lfo4;mso-layout-grid-align:none;text-autospace:

none">· If the particle size could be <0.5μm can easily exhale

<p class="MsoNormal" style="margin-bottom:0in;margin-bottom:.0001pt;text-align:

justify;line-height:normal">

<p class = "MsoListParagraphCxSpFirst" style = "margin: 0in; margin-bottom: .0001pt;

mso-add-space: auto; text-align: justify; line-height: normal ">SL NO:

<p class = "MsoListParagraphCxSpMiddle" style = "margin: 0in; margin-bottom: .0001pt;

mso-add-space: auto; text-align: justify; line-height: normal ">Voie d'administration

<p class = "MsoListParagraphCxSpMiddle" style = "margin: 0in; margin-bottom: .0001pt;

mso-add-space: auto; text-align: justify; line-height: normal ">Drogues

<p class = "MsoListParagraphCxSpLast" style = "margin: 0in; margin-bottom: .0001pt;

mso-add-space: auto; text-align: justify; line-height: normal ">Avantages

Marketed Products

Table no: 03 Current marketed products of nanosuspension formulations

<table border="1" cellpadding="0" cellspacing="0" class="PlainTable1" style="border-collapse:collapse;border:none;mso-border-alt:solid #BFBFBF .5pt;
mso-border-themecolor:background1;mso-border-themeshade:191;mso-yfti-tbllook:
1184;mso-padding-alt:0in 5.4pt 0in 5.4pt;width: 100%" width="554">

<td nowrap="nowrap" style="width:35.5pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;mso-border-alt:

solid #BFBFBF .5pt;mso-border-themecolor:background1;mso-border-themeshade:

191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="47">

Sl no

<td nowrap="nowrap" style="width:70.05pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-left:none;

mso-border-left-alt:solid #BFBFBF .5pt;mso-border-left-themecolor:background1;

mso-border-left-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:

25.55pt" valign="top" width="93">

Drugs

<td nowrap="nowrap" style="width:52.6pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-left:none;

mso-border-left-alt:solid #BFBFBF .5pt;mso-border-left-themecolor:background1;

mso-border-left-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:

25.55pt" valign="top" width="70">

Produit

<td nowrap="nowrap" style="width:70.3pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-left:none;

mso-border-left-alt:solid #BFBFBF .5pt;mso-border-left-themecolor:background1;

mso-border-left-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:

25.55pt" valign="top" width="94">

Method

<td nowrap="nowrap" style="width:88.05pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-left:none;

mso-border-left-alt:solid #BFBFBF .5pt;mso-border-left-themecolor:background1;

mso-border-left-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:

25.55pt" valign="top" width="117">

Company name

<td nowrap="nowrap" style="width:98.9pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-left:none;

mso-border-left-alt:solid #BFBFBF .5pt;mso-border-left-themecolor:background1;

mso-border-left-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:

25.55pt" valign="top" width="132">

Indication

<td nowrap="nowrap" style="width:35.5pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-top:none;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:

background1;mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;

height:25.55pt" valign="top" width="47">

1

<td nowrap="nowrap" style="width:70.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="93">

Fenofibrate

<td nowrap="nowrap" style="width:52.6pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="70">

Triglide

<td nowrap="nowrap" style="width:70.3pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="94">

Media milling

<td nowrap="nowrap" style="width:88.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="117">

Abbott pharma

<td nowrap="nowrap" style="width:98.9pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="132">

Hypercholesterolemia

<td nowrap="nowrap" style="width:35.5pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-top:none;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:

25.55pt" valign="top" width="47">

2

<td nowrap="nowrap" style="width:70.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="93">

Fenofibrate

<td nowrap="nowrap" style="width:52.6pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="70">

Tricor

<td nowrap="nowrap" style="width:70.3pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="94">

HPH

<td nowrap="nowrap" style="width:88.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="117">

First Horizon Pharma

<td nowrap="nowrap" style="width:98.9pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="132">

Hypercholesterolemia

<td nowrap="nowrap" style="width:35.5pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-top:none;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:

background1;mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;

height:25.55pt" valign="top" width="47">

3

<td nowrap="nowrap" style="width:70.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="93">

Megestrol acetate

<td nowrap="nowrap" style="width:52.6pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="70">

Megace

<td nowrap="nowrap" style="width:70.3pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="94">

Media milling

<td nowrap="nowrap" style="width:88.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="117">

PAR Pharma

<td nowrap="nowrap" style="width:98.9pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="132">

Appetite stimulant

<td nowrap="nowrap" style="width:35.5pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-top:none;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:

25.55pt" valign="top" width="47">

4

<td nowrap="nowrap" style="width:70.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="93">

Sirolimus

<td nowrap="nowrap" style="width:52.6pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="70">

Rapamune

<td nowrap="nowrap" style="width:70.3pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="94">

Media milling

<td nowrap="nowrap" style="width:88.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="117">

Wyeth

<td nowrap="nowrap" style="width:98.9pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="132">

Immunosuppressant

<td nowrap="nowrap" style="width:35.5pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-top:none;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:

background1;mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;

height:25.55pt" valign="top" width="47">

5

<td nowrap="nowrap" style="width:70.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="93">

Griseofulvin

<td nowrap="nowrap" style="width:52.6pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="70">

Gris-PEG

<td nowrap="nowrap" style="width:70.3pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="94">

Co-precipitation

<td nowrap="nowrap" style="width:88.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="117">

Novartis

<td nowrap="nowrap" style="width:98.9pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="132">

Antifungal

<td nowrap="nowrap" style="width:35.5pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-top:none;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:

25.55pt" valign="top" width="47">

6

<td nowrap="nowrap" style="width:70.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="93">

Cyclosporine

<td nowrap="nowrap" style="width:52.6pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="70">

<td nowrap="nowrap" style="width:70.3pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="94">

HPH

<td nowrap="nowrap" style="width:88.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="117">

<td nowrap="nowrap" style="width:98.9pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="132">

Immunosuppressant

<td nowrap="nowrap" style="width:35.5pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-top:none;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:

background1;mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;

height:25.55pt" valign="top" width="47">

7

<td nowrap="nowrap" style="width:70.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="93">

Spironolactone

<td nowrap="nowrap" style="width:52.6pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="70">

<td nowrap="nowrap" style="width:70.3pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="94">

HPH

<td nowrap="nowrap" style="width:88.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="117">

<td nowrap="nowrap" style="width:98.9pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="132">

Diuretic

<td nowrap="nowrap" style="width:35.5pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-top:none;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:

25.55pt" valign="top" width="47">

8

<td nowrap="nowrap" style="width:70.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="93">

Itraconazole

<td nowrap="nowrap" style="width:52.6pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="70">

<td nowrap="nowrap" style="width:70.3pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="94">

Precipitation

<td nowrap="nowrap" style="width:88.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="117">

<td nowrap="nowrap" style="width:98.9pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="132">

Antifungal

<td nowrap="nowrap" style="width:35.5pt;border:solid #BFBFBF 1.0pt;

mso-border-themecolor:background1;mso-border-themeshade:191;border-top:none;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:

background1;mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:

background1;mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;

height:25.55pt" valign="top" width="47">

9

<td nowrap="nowrap" style="width:70.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="93">

Nabilone

<td nowrap="nowrap" style="width:52.6pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="70">

Cesamet

<td nowrap="nowrap" style="width:70.3pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

background1;mso-border-bottom-themeshade:191;border-right:solid #BFBFBF 1.0pt;

mso-border-right-themecolor:background1;mso-border-right-themeshade:191;

mso-border-top-alt:solid #BFBFBF .5pt;mso-border-top-themecolor:background1;

mso-border-top-themeshade:191;mso-border-left-alt:solid #BFBFBF .5pt;

mso-border-left-themecolor:background1;mso-border-left-themeshade:191;

mso-border-alt:solid #BFBFBF .5pt;mso-border-themecolor:background1;

mso-border-themeshade:191;background:#F2F2F2;mso-background-themecolor:background1;

mso-background-themeshade:242;padding:0in 5.4pt 0in 5.4pt;height:25.55pt" valign="top" width="94">

Co-precipitation

<td nowrap="nowrap" style="width:88.05pt;border-top:none;

border-left:none;border-bottom:solid #BFBFBF 1.0pt;mso-border-bottom-themecolor:

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Lilly

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Anti-emetic

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dix

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Aprepitant

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Emend

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Media milling

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Merck Pharma

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Anti-emetic

Conclusion : Nanosuspensions appear to be unique & yet commercially viable approach to combating problems such as poor bioavailability that are associated with the delivery of hydrophobic drugs, including those that are poorly soluble in aqueous as well as organic media. The dissolution problems of poorly water soluble drugs have been largely solved to improve drug absorption & bioavailability. Nanosuspension technology can be combined with traditional dosage forms: tablets, capsules, pellets, & can be used for parenteral products. To take advantages of nanosuspension drug delivery, simple formulation technologies & variety applications, nanosuspensions will continue to be interest as oral formulations & non-oral administration develop in the future.

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