Novel use of superdisintegrants as viscosity enhancing agents in biocompatible polymer films containing griseofulvin nanoparticles

Abstract

The advantages of using superdisintegrants, sodium starch glycolate (SSG), croscarmellose sodium (CCS) and crospovidone (CP) over traditional high molecular weight (MW) viscosity enhancing agents, guar gum (GG), xanthan gum (XG), pectin and high MW HPMC are examined for improving drug content uniformity without compromising dissolution of films containing nanoparticles of griseofulvin (GF), used as a model poorly water-soluble drug. Films were fabricated by preparing low MW HPMC solutions to which a fixed amount of viscosity enhancing agents was added and mixed with GF nanosuspensions produced via wet milling, followed by casting and drying. The addition of superdisintegrants and high MW HPMC led to an increase in viscosity of precursor suspensions without GF particle aggregation, and hence excellent drug content uniformity along with retention of the high surface area of the GF nanoparticles in dried films. In contrast, the addition of XG and pectin resulted in aggregation of GF particles in suspensions, leading to poor content uniformity and incomplete recovery of GF nanoparticles upon redispersion of dried films. In spite of their high precursor viscosity, the films containing superdisintegrants did not lead to increased mechanical strength and demonstrated fast drug release, suggesting faster matrix erosion. In contrast, films with high MW polymers (GG, XG, and pectin and high MW HPMC) had increased mechanical strength and their subsequent slow erosion/disintegration along with longer hydration times resulted in significant delay of drug release, which was found to be directly proportional to their MW. These results demonstrate novel use for superdisintegrants as economical and superior alternative to traditional viscosity enhancing agents in forming drug laden biocompatible polymer films.