Impact of Physicochemical Properties of Cellulosic Polymers on Supersaturation Maintenance in Aqueous Drug Solutions

Abstract

The precipitation inhibitory effect of cellulosic polymers in relation to their physicochemical properties was studied. Using a poorly water-soluble model drug, griseofulvin, the precipitation inhibitory effect of a series of hydroxypropyl methylcellulose (HPMC) and methylcellulose polymers was studied using solvent–shift method. The extent of supersaturation maintenance of each polymer was then quantified by the parameter, supersaturation factor (SF). Partial least square (PLS) regression analysis was employed to understand the relative contribution from viscosity, hydroxypropyl content (HC), methoxyl content, methoxyl/hydroxypropyl ratio, and drug–polymer interaction parameter (χ) on SF. All grades of cellulosic polymers effectively prolonged supersaturation of griseofulvin. PLS regression analysis revealed that HC and χ appeared to have the strongest influence on SF response. A regression model of SF = 1.65–0.16 χ + 0.05 HC with a high correlation coefficient, r of 0.921, was obtained. Since the value of χ is inversely related to the strength of drug–polymer interaction, the result shows that SF increases with increasing drug–polymer interaction and increasing HC. As such, it can be implied that strong drug–polymer interaction and presence of hydroxypropyl groups in cellulosic polymers for hydrogen bonding are two key parameters for effective supersaturation maintenance. This knowledge on the relative contribution of polymer physicochemical properties on precipitation inhibition will allow the selection of suitable cellulosic polymers for systematic development of supersaturating drug delivery systems.