Disintegration Mediated Controlled Release Supersaturating Solid Dispersion Formulation of an Insoluble Drug: Design, Development, Optimization, and In Vitro Evaluation
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- 作者：Sanjay Verma ; Varma S. Rudraraju
- 关键词：cilostazol ; controlled release ; disintegration ; mediated controlled release (DMCR) ; extreme vertices mixture design (EVMD) ; solid dispersion
- 刊名：AAPS PharmSciTech
- 出版年：2015
- 出版时间：February 2015
- 年：2015
- 卷：16
- 期：1
- 页码：85-97
- 全文大小：1,988 KB
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- 出版者：Springer US
- ISSN：1530-9932
文摘
The objective of this study was to develop a solid dispersion based controlled release system for drug substances that are poorly soluble in water. A wax-based disintegration mediated controlled release system was designed based on the fact that an amorphous drug can crystallize out from hydrophilic matrices. For this study, cilostazol (CIL) was selected as the model drug, as it exhibits poor aqueous solubility. An amorphous solid dispersion was prepared to assist the drug to attain a supersaturated state. Povidone was used as carrier for solid dispersion (spray drying technique), hydrogenated vegetable oil (HVO) as wax matrix former, and sodium carboxymethyl cellulose (NaCMC) as a disintegrant. The extreme vertices mixture design (EVMD) was applied to optimize the designed and developed composition. The optimized formulation provided a dissolution pattern which was equivalent to the predicted curve, ascertaining that the optimal formulation could be accomplished with EVMD. The release profile of CIL was described by the Higuchi’s model better than zero-order, first-order, and Hixson-Crowell’s model, which indicated that the supersaturation state of CIL dominated to allow drug release by diffusion rather than disintegration regulated release as is generally observed by Hixson-Crowell’s model. The optimized composition was evaluated for disintegration, dissolution, XRD, and stability studies. It was found that the amorphous state as well as the dissolution profile of CIL was maintained under the accelerated conditions of 40°C/75% RH for 6?months.