Effect of water-soluble polymers on the aqueous solutility and complexing abilities of bropirimine with dimethyl-ß and hydroxypropyl-ß- cyclodextrin

Abstract

Bropirímine (2-amino-5-bromo-6-phenyl-4(3 )-pyrimidinone, ABPP) is an orally active immunomodulator that increases endogenous alpha-interfcron and other cytokines. Its low aqueous solubilily determines a low oral bioavailability (1 ), Cyclodextrins CD are water-soluble, hydrophobic torus-shapcd cyclic oligosaccharides, that can accommodate in their cavities water-insoluble drugs to form water-soluble inclusion complexes. Because of these properties CD have been used to enhance drug solubility, stability and bioavailabilíty (2-4). Hydroxypropyl β-cyclodextrin derivatives have been extensively used in pharmaceutical formulation owing 10 its high water solubilily (>50 % w/v) and low toxicity (5-6). Bcsides, methylated β-cyclodextrins show an improvement on water solubility of the natural parent and thc complexation capability improves significantly (7). Polymers are know to interact with CDs and, it have been shown that at low concentrations, hydrophilic polymers, such as hydroxypropyl rnethylcellulose (HPMC), carboximethylcellulose sodium salt (CMC Na) or polyvinylpyrrolidone (PVP), increase the complexing abilities of CDs (8). The purpose of this study was to investígate thc effect of various water-soluble polymers on the cyclodextrin complexation of bropirirnine. The efficiency of complexatíon was evaluated by determining the solubilizing effects of two cyclodextrin derivatives, dimethyl-β - and hydroxypropyl-β-cyclodextrin