Formulation of poly(D,L-lactide-co-glycolide) microspheres for inhalation in the dry state

On the basis that the residence time of drugs can be enhanced in a carrier system, the hypothesis of this work was that the respirable fraction (RF) of drugs delivered by dry powder inhalers (DPIs) can be improved more effectively by using hydrophobic microspheres as carriers. Poly (D,L-lactide-co-glycolide) microspheres (PLGA) were prepared in the respirable size range (3-7 {dollar}mu{dollar}m) with zeta potential (ZP) of {dollar}-{dollar}30.6 mV.; To enhance deaggregation during administration from DPIs, the surface properties of microspheres were altered by preparing powders with different surface charge and moisture contents. Microspheres were treated with suspensions of polylysine (PL) and polyglutamic acid (PGA) in isopropanol (IPA), obtaining ZPs of +55 and {dollar}-{dollar}55 mV, respectively. A third treatment was with IPA alone, which yielded a ZP of {dollar}-{dollar}36.7 mV. Microspheres with moisture contents from 0.40 to 2.47% were prepared by incubation for different durations in a 98% humidity chamber.; The powder formulations were evaluated for their degree of aggregation by cascade impaction using the Pfeiffer DPI. The IPA treated PLGA microspheres had a significantly higher RF (12.94%) as compared to the PL and PGA treated microspheres (3.29 and 2.42%, respectively), and also the untreated PLGA microspheres (3.84%). There was no apparent relation between the RF and ZP, but the determination of electrostatic charge by electrical-single particle aerodynamic relaxation time analysis suggested that the higher RF for the IPA formulation may be due to its highly unipolar nature (+56.3 {dollar}mu{dollar}C/g). A moisture content in the range of 0.66% in the microspheres appears to be optimum to increase the RF, by reducing the generation of electrostatic charges and capillary forces.; {dollar}sp{lcub}111{rcub}{dollar}In labeled PLGA microspheres were prepared with the IPA formulation to determine their in-vitro/in-vivo RFs via cascade impaction and intranasal administration to the rat. The RFs of the IPA treated microspheres were significantly larger than the corresponding values for the untreated microspheres, and an adequate fraction (20 to 30%) of the deposited radioactivity was in the lung area.