Amorphous solid dispersion (SD) technique has been used for improving the solubility and bioavailability of poorly water-soluble compounds. However, the stability of these SD is a concern due to the high propensity of metastable amorphous form to convert into its stable crystalline form. In this study, the stability of SD of griseofulvin (GSV), a high crystallization tendency compound, was evaluated in the presence of commonly used Food and Drug Administration-approved hydrophilic polymers such as polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose, Eudragits, and polyethylene glycol. Physical mixtures (PM) and SD were prepared at various drug to polymer ratios (3:1, 1:1, 1:2, 1:9 w/w) using the solvent evaporation technique. PM and SD were characterized by powder X-ray diffractometer and modulated differential scanning calorimetry to confirm the formation of amorphous dispersions and to understand the crystallization inhibition effectiveness of polymers. Infrared (IR), Raman spectroscopy, and molecular modeling were used to understand the role of interaction between GSV and polymers for stabilization of dispersions. We observed that most polymers are ineffective in stabilizing the amorphous form of GSV at low concentrations, that is, 3:1, 1:1, and 1:2 w/w except for PVP K-90, which was effective at a concentration of 1:1 w/w. Slight peak shifts were observed in IR and Raman; however, these shifts were inconclusive of molecular interactions between GSV and hydrophilic polymers. GSV's high crystallization tendency coupled with a lack of hydrogen bond acceptors/donors hinders the formation of stable SD, and thus, a higher polymer concentration is a prerequisite for their long-term stability.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery