Ritonavir is an antiretroviral drug characterized by low solubility and high permeability which corresponds to BCS class II drug. The purpose of the study was to develop solid dispersion by different methods and investigate them for in vitro and in vivo performance for enhancing dissolution and bioavailability, respectively. Since the drug possesses food-related absorption, the effect of biorelevant media (FaSSIF and FeSSIF state) on dissolution behavior was also studied. The solid dispersion was prepared using Gelucire as carrier in 1:4 ratio by different methods and were characterized for differential scanning calorimetry (DSC), X-ray diffractometry, scanning electron microscopy, and FT-IR. Oral bioavailability of 10 mg of ritonavir in solid dispersion prepared by solvent evaporation (SE1) and melt method (MM1) was compared with pure drug after oral administration of solid dispersion and pure drug to Albino Wistar rats of either sex. The results suggested formation of eutectic solid dispersion. In vitro dissolution studies was performed in 0.1 N HCl and biorelevant media showed enhanced dissolution rate as compared to pure drug in both FeSSIF media and 0.1 N HCl. The apparent rate of absorption of ritonavir from SE1 (C(max) 20221.37 ng/ml, t(max) 0.5 h) was higher than that of MM1 (C(max) 2,462.2, t(max) 1 h) and pure drug (C(max) 1,354.8 ng/ml, t(max) 0.5 h). On the basis of the result obtained, it was concluded that solid dispersion is a good approach to enhance solubility and bioavailability of poorly water-soluble ritonavir.
Formulation of solid dispersion in water-soluble carriers has been widely researched over the past four decades for solubility and related bioavailability enhancement. Despite 40 years of active research, there has not been much products in market based on this technique. The main reason for this being stability and scale up problems associated with this method, as reported by several authors. Strategies used for overcoming these problems and factors affecting formation of solid dispersion such as glass transition temperature and interaction of drug with polymer have been dealt conceptually in this review. The advent of surface-active carriers such as Gelucires, Poloxamers, and lipid-based carriers has given a new dimension for the successful development of solid dispersions by combating the problems associated with stability and also giving products with enhanced dissolution rate. Therefore, the article also discusses properties of such carriers that are being unraveled lately for formulation of solid dispersion. Characterization of solid dispersion to detect the change from crystalline to amorphous states and vice versa is an important tool for its formulation and determination of stability; thus, all the methods that are available for characterizations are discussed in this article with emphasis on the principle of the technique and its application.
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