FORMULATING β-CYCLODEXTRIN INCLUSION COMPLEXES FOR SOLUTION STABILITY ENHANCEMENT OF GRISEOFULVIN

Abstract

Griseofulvin is a poorly soluble antifungal antibiotic drug, the solubility of which can be enhanced by complexation with β-cyclodextrin. The inclusion complex was prepared by Physical and Kneading method in various molar ratios of 1:1, 1:2 and 2:1 of the drug and β-cyclodextrin, respectively. IR spectra of drug, polymer and a physical mixture of drug and polymer were obtained using FT-IR. The inclusion complex was characterized and evaluated by determination of aqueous solubility, determination of pH stability, estimation of griseofulvin in complexes and stability study. The aqueous solubility of the GCD inclusion complexes was determined using the Higuchi-Connor method. The results indicated that the use of kneading method for preparation of complexes was more effective than the physical mixture method. The inclusion complexes were on the other hand was able to prevent the degradation of griseofulvin at all the pH. The degradation of griseofulvin from the inclusion complexes was found to be prevented and around 20-35% drug degraded in the acidic buffer while 40-50% drug degraded in the neutral and alkaline buffers. It was very much evident from the stability data that the inclusion complexes were helpful in improving the solution stability of griseofulvin. Complex F5 was used as the complex of choice for stability analysis as it exhibited the highest aqueous solubility amongst all the inclusion complexes that were prepared. The results reveal that the kneading method was helpful in incorporating higher amount of griseofulvin in the complex, the inclusion complex of griseofulvin (F5) was subjected to short term accelerated stability testing by storing the complexes at room temperature and at 45ºC. The samples were analyzed at an interval of one week, three weeks and six weeks for their physical appearance and drug content values. No appreciable changes observed with the above parameters.