POLY(L-LACTIC ACID) MICROSPHERES FOR PULMONARY DRUG-DELIVERY - RELEASE KINETICS AND AEROSOLIZATION STUDIES

We have previously developed poly(L-lactic acid) (PLA) microspheres co ntaining nedocromil sodium and beclomethasone dipropionate (BDP) for a erosolisation to the respiratory tract (El-Baseir, M.M., Phipps, M.A., Kellaway, I.W., Preparation and subsequent degradation of poly(L-lact ic acid) microspheres suitable for aerosolisation: a physico-chemical study. Int. J. Pharm. 151 (1997) 145-153). In this study we have inves tigated the in vitro release kinetics of these two drugs from PLA micr ospheres and the deposition of the microspheres in an in vitro lung mo del (Andersen cascade impactor) following aerosolisation from a dry po wder inhaler (Spinhaler(R)). The in vitro kinetics of drug release rev ealed a controlled release of nedocromil sodium over 8 days with a bur st effect (27-60%, w/w) which varied with the particle size of the mic rospheres. For BDP entrapped in PLA microspheres, controlled release o f BDP occurred over 6 days. BDP release was determined by measuring th e shift in the phase transition temperature of dimyristoylphosphatidyl choline (DMPC) liposomes induced by partitioning of the steroid into t he lipid bilayers. The residual poly(vinyl alcohol) used as an emulsif ier in the production of the microspheres was <7% (w/w). The in vitro deposition of the microspheres (1.00 +/- 0.21 mu m) containing BDP fro m a Spinhaler(R) to a cascade impactor at a flow rate of 60 l/min, res ulted in 20% of the emitted dose deposited on stages corresponding to particles <3 mu m and approximately 42% <5 mu m. (C) 1998 Elsevier Sci ence B.V. All rights reserved.