EFFECT OF SURFACE-TREATMENT ON THE RESPIRABLE FRACTIONS OF PLGA MICROSPHERES FORMULATED FOR DRY POWDER INHALERS

An investigation of the degree of aggregation of dry powders with diff erent surface charge and moisture contents was carried out using poly( D,L-lactide-co-glycolide) (PLGA) microspheres. Microspheres were prepa red in the respirable size range (3-7 mu m) with an estimated zeta pot ential (ZP) of - 30.6 mV. Suspensions of polylysine (PL) and polygluta mic acid (PGA) in isopropanol were used to treat the microspheres to o btain ZPs of +/-60 mV, respectively. Treatment with isopropanol (IPA) alone yielded a ZP of - 36.7 mV, which was similar to the untreated mi crospheres - 30.6 mV. Respirable fractions (RFs) were determined by ca scade impaction using a prototype DPI. The IPA-treated formulation was the most deaggregated of the studied samples as indicated by a signif icantly higher RF (12.9) compared to the PL and PGA formulations (3.29 and 2.42, respectively) and the untreated PLGA microspheres (3.84). M icrospheres with moisture contents in the range of 0.40-2.47% were stu died and a moisture content of 0.66% resulted in the highest relative deaggregation of the PLGA microspheres. Measurement of the surface cha rge and mass median aerodynamic diameter in the dry state byelectrical -single particle aerodynamic relaxation time analysis (E-SPART) sugges ted that the higher RF for the IPA formulation may be due to its highl y unipolar nature, i.e. a net charge of + 56.3 mu C/g, as compared to net charges in the range of 34.3-38.4 mu C/g for the other microsphere s. Formulation of microspheres for use in DPIs must proceed on a case by case basis as certain approaches can enhance aggregation. (C) 1997 Elsevier Science B.V.