The development of a dense gas solvent exchange process for the impregnation of pharmaceuticals into porous chitosan

Abstract

The aim of this study was to prepare stable formulations of poorly water-soluble drugs in amorphous forms to enhance their dissolution rates, promote the bioavailability, minimize the dosage, thereby theoretically decreasing their side effects. A dense gas solvent exchange process was developed for the impregnation of poorly water-soluble drugs such as camptothecin and griseofulvin into a chitosan matrix. The amount of drug impregnated was measured by UV-spectrophotometery and gravimetric techniques. Pore characteristics and the crystallinity of the drugs in the impregnated chitosan were measured. Homogenous nano-sized pores with thin walls were formed in chitosan using the dense gas solvent exchange process. The method was efficient for the impregnation of a drug into chitosan. Results of XRD, Fourier transform infrared spectroscopy and differential scanning calorimetry demonstrated that as a result of interaction between chitosan and the drug, both camptothecin and griseofulvin were in amorphous forms after processing. The dissolution rate of processed griseofulvin was increased threefold due to the hydrophilic properties of chitosan and its interaction with the drug. A new approach was developed for promoting drug bioavailability that has the potential to decrease the required dose and side effects, particularly for chemotherapeutic drugs with narrow therapeutic index.