ON THE RELATIONSHIP BETWEEN DRUG AND CARRIER DEPOSITION FROM DRY POWDER INHALERS IN-VITRO

Dry powder inhaler formulations usually contain micronised drug partic les and lactose as a carrier. Although the line particle fraction (FPF ) of drug from many different formulations has been reported previousl y, there have been few studies which have determined the deposition of both drug and carrier. In this study, drug and lactose particle depos ition was characterised by means of a twin stage impinger (TSI) and an Andersen cascade impactor (ACI). The flow rate was varied between 28. 3-90 l/min. The particle size distribution of the lactose carrier in t he formulation highly influenced the drug FPF. The higher the flow rat e, the higher the FPF of drug when micronised lactose was employed in the formulation. However, when a larger particle size carrier (Lactoch em lactose) was employed in the formulation, the FPF was not changed w hen the flow rate increased (30-90 l/min). Deposition patterns of fine lactose carrier from each formulation at different air hows were broa dly similar to those of the drug. At 28.3 l/min, the drug particles we re deaggregated to a median particle size of 4.89 +/- 0.11 mu m (Lacto chem formulation) and 4.07 +/- 0.09 mu m (micronised lactose formulati on). When the flow rate was increased to 60 l/min, the degree of dispe rsion that resulted led to the deaggregation of the drug to particles with a median size of 2.80 mu m in both formulations. The coarser part icles of lactose in fractions of carrier containing a wide particle si ze distribution impacted in the throat and preseparator of the ACI and only particles less than 10 mu m entered stage 0 to stage 7. The medi an size of the lactose obtained in both formulations at a flow rate of 28.3 and 60 l/min varied between 5.67 mu m to 4.42 mu m and hence the carrier particles did not penetrate to stage 3 in the ACI. These resu lts show that in impactors the deposition pattern of both drug and car rier is highly dependent upon air flow rate and particle size distribu tion of the carrier used to prepare the formulation. (C) 1998 Elsevier Science B.V. All rights reserved.