In Vitro Evaluation of Drug Solubility and Gamma Irradiation on the Release of Betamethasone under Simulated In Vivo Conditions

In situ—forming biodegradable polymeric systems loaded with betamethasone (BTM) and betamethasone acetate (BTMA) (5, 7, and 10% (w/w)) were prepared using poly(DL-lactide-co-glycolide) (33% (w/w)), ethyl heptanoate (5% (w/w)), and N-methyl-2-pyrrolidone as biodegradable material, additive, and solvent, respectively. The effects of gamma irradiation, drug loading, and solvent removal on release profiles were evaluated. The drug release in phosphate-buffered solution (pH = 7.4, 37°C) was measured using high-performance liquid chromatography. The release profiles of irradiated and nonirradiated formulations based on BTMA showed a three-phase release pattern, whereas the pattern for BTM was biphasic. Gamma irradiation had no significant effect on the BTMA release profiles ( p>0.05). Unexpectedly, irradiation had a significant effect on release behavior of BTM ( p<0.05); also, the rate of BTM release was decreased with an increase in drug loading up to 10%. The amount of BTM that was released in the burst phase decreased by about 1.4 and 1.5 times for 7 and 10% BTM loading, respectively. The duration of BTM release was more than that of BTMA. Changes in hydrophobicity and hydrogen bonding had a strong effect on the release behavior of the two forms of BTM from the in situ—forming systems.