Dry powder formulations for inhalation of fluticasone propionate and salmeterol xinafoate microcrystals.
Direct crystallization of active pharmaceutical ingredient (API) particles in the inhalable size range of 1-6 microm may overcome surface energization resulting from micronization. The aerosolization of fluticasone propionate (FP) and salmeterol xinafoate (SX) microcrystals produced by aqueous crystallization from poly(ethylene glycol) solutions was investigated using a twin stage impinger following blending with lactose. Fine particle fractions from SX formulations ranged from 15.98 +/- 2.20% from SX crystallized from PEG 6000 to 26.26 +/- 1.51% for SX crystallized from PEG 400. The FPF of microcrystal formulations increased as the particle size of microcrystals was increased. The aerosolization of SX from DPI blends was equivalent for the microcrystals and the micronized material. FP microcrystals, which had a needlelike morphology, produced similar FPFs (PEG 400: 17.15 +/- 0.68% and PEG 6000: 15.46 +/- 0.97%) to micronized FP (mFP; 14.21 +/- 0.54). The highest FPF (25.66 +/- 1.51%) resulted from the formulation of FP microcrystals with the largest median diameter (FP PEG 400B: 6.14 +/- 0.17 microm). Microcrystallization of SX and FP from PEG solvents offers the potential for improving control of particulate solid state properties and was shown to represent a viable alternative to micronization for the production of particles for inclusion in dry powder inhalation formulations.
King's College London, Drug Delivery Research Group, Pharmaceutical Science Division, London, United Kingdom.
Darragh
D
Murnane
Gary P
GP
Martin
Christopher
C
Marriott
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000737:chemistry*; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D000730:Androstadienes / Q000008:administration & dosage / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004339:Drug Compounding; D000068298:Fluticasone; D007785:Lactose / Q000737:chemistry; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011208:Powders; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D000336:Aerosols; D000730:Androstadienes; D001993:Bronchodilator Agents; D011208:Powders; D011092:Polyethylene Glycols; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D007785:Lactose; D000420:Albuterol