Characterization and in vitro release of minocycline hydrochloride microspheres prepared via coacervation

Abstract

Coacervation is a commonly used method for protein and peptide drug microencapsulation using biodegradable or bioresorbable polymers. However, there is a lack of literature focused on microencapsulation of small molecule drugs using coacervation techniques. In addition, the apparatus used for this microencapsulation method has not been well-described. The objectives of the present work were to: (1) establish a reliable apparatus for coacervation microencapsulation; (2) investigate the impact of the viscosity of the silicone oil used in processing on microsphere performance; and (3) develop a reproducible in vitro release testing method for minocycline hydrochloride microspheres. Minocycline hydrochloride was chosen as the model drug and two compositionally equivalent microsphere formulations were prepared via coacervation using an in-house designed glass vessel assembly with a novel in-house customized paddle to achieve a relatively homogeneous particle size distribution. The critical physicochemical properties including drug loading, particle size, and morphology of the prepared microspheres and the commercial microspheres product (Arestin) were determined. In vitro release testing of the prepared microspheres as well as of Arestin was performed using a sample-and-separate method. The method showed good reproducibility and discriminatory ability. The physicochemical properties (such as particle size) as well as the in vitro release characteristics of the prepared microspheres were determined to be sensitive to the viscosity of the silicone oil used in coacervation processing. The silicone oil with higher viscosity (1000 cSt) used during the coacervation process resulted in smaller particle sized microspheres and consequently caused a higher initial burst release. Whereas, the silicone oil with lower viscosity resulted in larger sized microspheres with low burst release and a slower drug release rate.