Poly(L-lactic acid) microspheres for pulmonary drug delivery: release kinetics and aerosolization studies

We have previously developed poly(L-lactic acid) (PLA) microspheres containing nedocromil sodium and beclomethasone dipropionate (BDP) for aerosolisation to the respiratory tract (El-Baseir, M.M., Phipps, M.A., Kellaway, I.W., Preparation and subsequent degradation of poly(L-lactic acid) microspheres suitable for aerosolisation: a physico-chemical study. Int. J. Pharm. 151 (1997) 145-153). In this study we have investigated the in vitro release kinetics of these two drugs from PLA microspheres and the deposition of the microspheres in an in vitro lung model (Andersen cascade impactor) following aerosolisation from a dry powder inhaler (Spinhaler(R)). The in vitro kinetics of drug release revealed a controlled release of nedocromil sodium over 8 days with a burst effect (27-60%, w/w) which varied with the particle size of the microspheres. For BDP entrapped in PLA microspheres, controlled release of BDP occurred over 6 days. BDP release was determined by measuring the shift in the phase transition temperature of dimyristoylphosphatidylcholine (DMPC) liposomes induced by partitioning of the steroid into the lipid bilayers. The residual poly(vinyl alcohol) used as an emulsifier 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 from a Spinhaler(R) to a cascade impactor at a flow rate of 60 l/min, resulted in 20% of the emitted dose deposited on stages corresponding to particles <3 mu m and approximately 42% <5 mu m. (C) 1998 Elsevier Science B.V. All rights reserved.