Optimization of a dry powder inhaler formulation of nacystelyn, a new mucoactive agent.
The aim of this study was to optimize a dry powder inhaler formulation containing a new mucoactive drug, nacystelyn. Formulations were made using three types of lactose, crystalline alpha-lactose, spray-dried lactose and a roller-dried anhydrous beta-lactose. The roller-dried anhydrous beta-lactose possessed the most adequate surface properties, resulting in a significantly higher (P < 0.05) in-vitro lung deposition of nacystelyn than the conventional crystalline alpha-lactose and spray-dried lactose. The particle size distribution of roller-dried beta-lactose was optimized also. Within the size ranges tested (63-100, 90-125 and 100-160 microm), the coarser the lactose, the higher the in-vitro deposition of the drug (up to 40%). In contrast, the in-vitro lung deposition of 100-160 microm roller-dried beta-lactose was very low (< 0.5%), so limiting the potential risk of lung irritation due to the carrier. The influence of the ratio of active ingredient/excipient (w/w) was also investigated. No difference was observed for mixtures from 1:2 to 1:4 while higher dilutions (1:5 and 1:6) showed significantly (P < 0.005) lower deposition results. Finally, the influence of the airflow rate was assessed. No dependence of the fine particle dose was observed between 40 and 80 L min(-1) while significantly higher results were obtained at 100 L min(-1). The dry powder inhaler formulation of nacystelyn using the unusual roller-dried anhydrous beta-lactose resulted in very high and reproducible in-vitro deposition results. However, the latter needs to be confirmed by in-vivo studies.
Vanderbist
F
F
Laboratoires SMB, Brussels, Belgium.
Wery
B
B
Moyano-Pavon
I
I
Moës
A J
AJ
D000111:Acetylcysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D000280:Administration, Inhalation; D002214:Capsules; D004337:Drug Carriers; D005100:Expectorants / Q000008:administration & dosage* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007785:Lactose; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D012995:Solubility
D002214:Capsules; D004337:Drug Carriers; D005100:Expectorants; C086501:N-acetylcysteine lysinate; D011208:Powders; D007785:Lactose; D008239:Lysine; D000111:Acetylcysteine