Solid Dispersion as an Approach for Bioavailability Enhancement of Poorly Water-Soluble Drug Ritonavir

Abstract

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.

Improved Bioavailability of Poorly Water-Soluble Drug Curcumin in Cellulose Acetate Solid Dispersion

“…In the spectra of the SRSD shown in Fig. 2e, the spectra of the SRSD and the PM were quite superimposable, except the absorption band of OH for CA and Cur which was shifted toward the lower frequency of 3,403 cm −1 , indicating the formation of an intermolecular hydrogen bond which would result in the increased solubility/dissolution of drug (22). However, no additional peak was observed depicting the absence of any chemical interaction between the drug and the carrier.…”

A Menthol-Based Solid Dispersion Technique for Enhanced Solubility and Dissolution of Sulfamethoxazole from an Oral Tablet Matrix

“…2b) ), F6 displaying the lowest value (1.12 J g −1 ), and F7 showing a complete absence of the drug peak. It was speculated that the decrease in intensity of the SMX peak is attributed to the dissolving of SMX within the melted menthol during DSC measurements and as a result, distinct endothermic peaks corresponding to the melting of menthol was observed (25)(26)(27). In addition, the results may indicate that the degree of crystallinity was substantially reduced and the SMX was present in an amorphous form within the solid dispersion, thus accounting for the reduced intensity and shifting peaks (25,26).…”

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization,in vitroandin vivoevaluation

“…Various strategies have been used to overcome the problems associated with oral absorption and bioavailability issues of poorly soluble drugs, such as particle size reduction (Aungst, 1993), complexation with cyclodextrins (Miyake et al, 2000), salt formation, solid dispersions (Sinha et al, 2010), use of surfactant, nanoparticles, nanocarriers (Bali et al, 2011), Nanoemulsions , self-emulsifying drug delivery system , prodrug formation, etc. Approaches used in past to improve the dissolution and bioavailability of NRG include complexation with b-cyclodextrin (Tommasini et al, 2004), phospholipid complexes (Semalty et al, 2010), solid dispersion with PVP (Kanaze et al, 2006), etc.…”