Evaluation of Griseofulvin Binary and Ternary Solid Dispersions with HPMCAS

The stability and dissolution properties of griseofulvin binary and ternary solid dispersions were evaluated. Solid dispersions of griseofulvin and hydroxypropyl methylcellulose acetate succinate (HPMCAS) were prepared using the spray drying method. A third polymer, poly[N-(2-hydroxypropyl)methacrylate] (PHPMA), was incorporated to investigate its effect on the interaction of griseofulvin with HPMCAS. In this case, HPMCAS can form H bonds with griseofulvin directly; the addition of PHPMA to the solid dispersion may enhance the stability of the amorphous griseofulvin due to greater interaction with griseofulvin. The X-ray powder diffraction results showed that griseofulvin (binary and ternary solid dispersions) remained amorphous for more than 19 months stored at 85% RH compared with the spray-dried griseofulvin which crystallized totally within 24 h at ambient conditions. The Fourier transform infrared scan showed that griseofulvin carbonyl group formed hydrogen bonds with the hydroxyl group in the HPMCAS, which could explain the extended stability of the drug. Further broadening in the peak could be seen when PHPMA was added to the solid dispersion, which indicates stronger interaction. The glass transition temperatures increased in the ternary solid dispersions regardless of HPMCAS grade. The dissolution rate of the drug in the solid dispersion (both binary and ternary) has significantly increased when compared with the dissolution profile of the spray-dried griseofulvin. These results reveal significant stability of the amorphous form due to the hydrogen bond formation with the polymer. The addition of the third polymer improved the stability but had a minor impact on dissolution

SMEDDS of Glyburide: Formulation, In Vitro Evaluation, and Stability Studies

The objective of the present investigation was to develop and evaluate self-microemulsifying drug delivery system (SMEDDS) for improving the delivery of a BCS class II antidiabetic agent, glyburide (GLY). The solubility of GLY in oils, cosurfactants, and surfactants was evaluated to identify the components of the microemulsion. The ternary diagram was plotted to identify the area of microemulsion existence. The in vitro dissolution profile of GLY SMEDDS was evaluated in comparison to the marketed GLY tablet and pure drug in pH 1.2 and pH 7.4 buffers. The chemical stability of GLY in SMEDDS was determined as per the International Conference on Harmonisation guidelines. The area of microemulsion existence increased with the increase in the cosurfactant (Transcutol P) concentration. The GLY microemulsion exhibited globule size of 133.5 nm and polydispersity index of 0.94. The stability studies indicated that GLY undergoes significant degradation in the developed SMEDDS. This observation was totally unexpected and has been noticed for the first time. Further investigations indicated that the rate of GLY degradation was highest in Transcutol P

Drug-Cyclodextrin-Vesicles Dual Carrier Approach for Skin Targeting of Anti-acne Agent

In the present study attempt was made for preparation of isotretinoin-hydroxypropyl β cyclodextrin (HP-β-CD) inclusion complex and encapsulate this complex in elastic liposomes to study the effect of dual carrier approach on skin targeting of isotretinoin. The isotretinoin HP-β-CD complex was prepared by freeze-drying method and characterized by IR spectroscopy. The drug and drug-CD complex loaded elastic liposomal formulation were prepared and characterized in vitro, ex-vivo and in vivo for shape, size, entrapment efficiency, no. of vesicles per cubic mm, in vitro skin permeation and deposition study, photodegradation and skin toxicity assay. The transdermal flux for different vesicular formulations was observed between 10.5 ± 0.5 to 13.9 ± 1.6 μg/cm2/h. This is about 15-21 folds higher than that obtained from drug solution (0.7 ± 0.1 μg/cm2/h) and 4-5 folds higher than obtained with drug-CD complex solution (2.7 ± 0.1 μg/cm2/h). The amount of drug deposit was found to increase significantly (p < 0.05) by cyclodextrin complexation (30.1 ± 0.1 μg). The encapsulation of this complex in elastic liposomal formulation further increases its skin deposition (262.2 ± 21 μg). The results of skin irritation study using Draize test also showed the significant reduction in skin irritation potential of isotretinoin elastic liposomal formulation in comparison to free drug. The results of the present study demonstrated that isotretinoin elastic liposomal formulation possesses great potential for skin targeting, prolonging drug release, reduction of photodegradation, reducing skin irritation and improving topical delivery of isotretinoin