Abstract. Efavirenz (EFV) is an oral antihuman immunodeficiency virus type 1 drug with extremely poor aqueous solubility. Thus, its gastrointestinal absorption is limited by the dissolution rate of the drug. The objective of this study was to characterize the inclusion complexes of EFV with β-cyclodextrin (β-CD), hydroxypropyl β-CD (HPβCD), and randomly methylated β-CD (RMβCD) to improve the solubility and dissolution of EFV. The inclusion complexation of EFV with cyclodextrins in the liquid state was characterized by phase solubility studies. The solid-state characterization of various EFV and CD systems was performed by X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy analyses. Dissolution studies were carried out in distilled water using US Pharmacopeia dissolution rate testing equipment. Phase solubility studies provided an A L -type solubility diagram for β-CD and A P -type solubility diagram for HPβCD and RMβCD. The phase solubility data enabled calculating stability constants (K s ) for EFV-βCD, EFV-HPβCD, and EFV-RMβCD systems which were 288, 469, and 1,073 M −1 , respectively. The physical and kneaded mixtures of EFV with CDs generally provided higher dissolution of EFV as expected. The dissolution of EFV was substantially higher with HPβCD and RMβCD inclusion complexes prepared by the freeze drying method. Thus, complexation with HPβCD and RMβCD could possibly improve the dissolution rate-limited absorption of EFV.

The objective of this study was to formulate genistein as a topical gel with various penetration enhancers for increased permeation and retention in human skin. The high performance liquid chromatography assay method was validated for precision and reproducibility. The intra-day and inter-day precision as represented by the coefficient of variation (CV) of the peak areas were <0.44% and <0.67%, respectively. Further, the reproducibility was demonstrated by the CV of the assay at different genistein concentrations, which were <1.64%. Genistein was subjected to various stress conditions to obtain basic information on the appropriate pH and aqueous vehicle for formulating topical gels. Genistein was highly stable under neutral and oxidative conditions, but degraded to highly polar and nonpolar compounds under basic and acidic conditions, respectively. Menthol produced a 9- and 22-fold increase in the flux and skin retention of genistein, respectively, after 24 h of gel application as compared with the control (no enhancer). Cineole showed an approximately 7-fold increase in flux, but skin retention did not increase significantly. Transcutol increased the flux and skin retention of genistein by 5- and 7-fold, respectively. When Transcutol was formulated with Lauroglycol, there was a 13- and 9-fold increase in the flux and skin retention, respectively. Incorporation of penetration enhancers into the topical gel increased the skin permeation of genistein, so that the target delivery rate for its therapeutic effects can be achievable based on the in vitro human skin data generated in this study.

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The knowledge of glass transition temperatures Tg in drug + polymer systems is indispensable for drug encapsulation. Tg values as a function of composition make possible the determination whether a given polymer is miscible or compatible with the drug and whether the polymer will provide release of the drug into organism within an acceptable rate range. We have used differential scanning calorimetry and Fourier‐transform infrared spectroscopy to evaluate miscibility in solid dispersions of the drugs carvedilol, itraconazole, nevirapine, and nimodipine in the pharmaceutical grade copolymer poly(vinyl pyrrolidone‐co‐vinyl acetate) (PLS‐630 Copovidone). Successful drug encapsulation is discussed in terms of thermophysical behavior (suppression of crystallization, negative excess volumes of mixing) and intermolecular interactions (concentrations of proton donating/accepting groups) in drug + polymer systems. Several equations were applied to the complex s‐shaped Tg(ϕ) patterns obtained (ϕ being the mass fraction of the drug). The best agreement of calculations with experiment is achieved using a recently proposed three‐parameter equation, symmetric with respect to the equal concentration of both components. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers