beta-Glucuronidase activity following complex coacervation and spray drying microencapsulation.
The objective was to develop a microencapsulation process suitable for the controlled release of an active protein drug. beta-glucuronidase was selected as a model protein and a combination of complex coacervation (gelatin/sodium alginate, gelatin/acacia and albumin/acacia) and spray drying was investigated. Coacervates were either spray dried or glutaraldehyde crosslinked to form microcapsules. Polyvinylpyrrolidone (PVP) and polyethylene glycol were investigated as potential coacervate enhancers and stabilizers. beta-glucuronidase/polymer mixtures were spray dried to determine any polymer protective effects on protein activity. A BUCHI 190 Spray Drier was used, beta-glucuronidase activity was determined using a Sigma Kit and microcapsule particle size was measured by Accusizer analysis (light blockage). All non-crosslinked coacervates investigated, with the exceptions of albumin/acacia and albumin/acacia/beta-glucuronidase/PVP, were unsuitable for spray drying as they rapidly phase separated and blocked the spray drier nozzle. beta-glucuronidase activity in the albumin/acacia coacervates approximated to 99% prior to and 80% following spray drying. This can be compared to activities of approximately 30% and 68% when spray dried alone and with albumin, respectively, and of 18% in albumin/acacia microcapsules crosslinked with glutaraldehyde. Microcapsule particle size was affected by coacervation pH, additives and spray drying. In vitro beta-glucuronidase release was biphasic, with an initial burst release followed by a zero order release phase and continued over the 12 day study period. In conclusion, the spray drying albumin/acacia/PVP method described is useful for the preparation and collection of controlled release microcapsules with minimal loss of beta-glucuronidase activity.
Burgess
D J
DJ
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs 06269, USA.
Ponsart
S
S
D000045:Acacia / Q000737:chemistry; D000418:Albumins / Q000737:chemistry; D002214:Capsules; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004795:Enzyme Stability; D005966:Glucuronidase / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D010316:Particle Size
D000418:Albumins; D002214:Capsules; D003692:Delayed-Action Preparations; D005966:Glucuronidase