Solvent exchange and drug release characteristics of doxycycline hyclate-loaded bleached shellac in situ-forming gel and -microparticle

Abstract

Doxycycline hyclate (DX)-loaded bleached shellac (BS) in situ forming gel (isg) and in situ microparticle (ism) were prepared using dimethyl sulfoxide (DMSO), N-methyl pyrrolidone (NMP) and 2-pyrrolidone (PYR) as solvents. Solvent and drug release characteristics of them were investigated. Diffusion rate of solvent applied in formulation was as following: DMSO > NMP > PYR. In situ forming systems comprising PYR had the slowest release rate of solvent and drug while water flowed into system in rank of solvent order as following: DMSO > NMP > PYR. Size and density of pores were increased by time similarly to release rate of solvent and drug. At steady state, total mass loss converted to PYR ≫ NMP > DMSO similarly to water content pattern. The solvent and DX release from ism were apparently slower than those from isg owing to barrier effect from oil component. The isg and ism prepared from DMSO exhibited the highly sponge-like structure than that using PYR which the later matrices eventually dissipated due to hydrolysis of BS which was accelerated by PYR-induced water accumulation. PYR was the most appropriated solvent for BS isg and ism because their formulations demonstrated the proper sustained drug release and preferable self-degradation.

Keywords: Bleached shellac; Doxycycline hyclate; Drug release; In situ-forming gel; In situ-forming microparticle; Solvent exchange.