Lactose modifications enhance its drug performance in the novel multiple dose Taifun® DPI

Drug-carrier particle interactions greatly affect the detachment of drug from the carrier in inhalation powders. In this study, a novel multiple dose, reservoir-based Taifun(R) was used as a dry powder inhaler, and the effects of carrier physical properties were evaluated on the pulmonary deposition of budesonide, along with physical stability of the inhalation powder. In this study; untreated commercial preparation of alpha-lactose monohydrate, highly amorphous spray dried lactose, crystallized spray dried lactose, Flowlac-100(R) and Flowlac-100(R) mixed with crystalline micronized lactose were used as carriers. Dry powder formulations were prepared by the suspension method, where the budesonide-carrier ratio was 1:15.1 (w/w). Carriers and formulations were initially characterized, and again after 1 month's storage at 40 degreesC/75% RH. The physical properties of the carriers strongly affected the pulmonary deposition of budesonide and the physical stability of the inhalation powder. Initially, amorphous contents of the carriers were 0-64%, but spontaneous crystallisation of the amorphous lactose occurred during storage and, thus all carriers were 100% crystalline after storage. When compared to an untreated alpha-lactose monohydrate, the highly amorphous spray dried lactose and Flowlac-100(R) did not improve aerosol performance of the inhalation powder. When crystalline spray dried lactose was used as a carrier, the highest RF% values were achieved, and RF % values did not alter during storage but the emitted budesonide dose was lower than the theoretical dose. When Flowlac-100(R) mixed with crystalline micronized lactose was used as a carrier, the emitted budesonide dose was close to the theoretical dose, and high RF % values were achieved but these changed during storage. (C) 2002 Elsevier Science B V All rights reserved.