Formulation development and in vitro evaluation of oral extended-release capsules containing biodegradable microspheres

Abstract

Oral extended-release delivery of Biopharmaceutics Classification System (BCS) class II and III compounds is desirable in order to decrease dosing frequency and potential adverse effects. Maintaining an extended-release profile of the drug is ideal to minimize fluctuations in plasma concentrations. The main objective of this research was to formulate a polymeric microsphere drug delivery system that will effectively provide extended-release characteristics via an orally administered capsule. Using acetaminophen and ibuprofen as model drugs, this drug delivery system was shown to provide extended-release characteristics of the drug for enhanced efficacy. The biodegradable polymeric matrix was formulated using bovine serum albumin (BSA) with glutaraldehyde as the crosslinker. The drug of interest was then encapsulated into the polymeric matrix and spray-dried into microspheres. Once prepared, the drug-loaded microsphere powder was placed into hard gelatin capsules. The physicochemical properties of the microsphere formulations were characterized. Additionally, differential scanning calorimetry was utilized to examine the thermal stability of the encapsulated drug. Release studies were conducted in vitro to examine the release profile of the drug. Cell uptake studies were carried out to examine the internalization capability of microsphere formulations. Drug-loaded microspheres were found to be approximately 2 microns in size and exhibited a uniform size distribution. Zeta potential measurements were shown to be approximately -30 mV, which indicated that the microspheres are stable in dispersions. Release data showed a constant release of the drug from the microsphere and capsule formulations for at least 16 hours. Formulated microspheres were able to be internalized into human intestinal Caco-2 cells. These data provided evidence for the role of the microsphere delivery system in the extended-release delivery of BCS Class II and III drug substances. © 2014 Enriquez GG, et al.