Novel pMDI formulations for pulmonary delivery of proteins.
In this paper, we demonstrate that co-spray-drying a model protein with sodium carboxymethylcellulose (NaCMC) protects protein integrity during spray-drying, and that the resultant spray-dried powders can be successfully dispersed in hydrofluoroalkane (HFA) propellant to prepare pressurised metered dose (pMDI) formulations that exhibit high respirable fractions. The spray-dried powders were formulated as HFA-134a pMDI suspensions in the absence of any other excipients (e.g. surfactants) or co-solvents (e.g. ethanol). The in vitro aerosolisation profile of these systems was assessed using the twin stage impinger; fine particle fractions (FPF) > or = 50% of the recovered dose were obtained. Following storage for five months, the aerosolisation performance was reassessed; the NaCMC-free formulation demonstrated a significant decrease in FPF, whereas the performance of the NaCMC-modified formulations was statistically equivalent to their initial performance. Thus, formulation of pMDI suspensions using NaCMC-based spray-dried powders is a promising approach for the pulmonary delivery of proteins and peptides.
Li
Hao-Ying
HY
School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
Seville
Peter C
PC
D000280:Administration, Inhalation; D000335:Aerosol Propellants / Q000737:chemistry; D000336:Aerosols; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D036501:Metered Dose Inhalers; D010316:Particle Size; D011208:Powders; D055550:Protein Stability; D019141:Respiratory System Agents / Q000008:administration & dosage / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry*; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014783:Viscosity; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000336:Aerosols; D002266:Carboxymethylcellulose Sodium; D005079:Excipients; D006845:Hydrocarbons, Fluorinated; D011208:Powders; D019141:Respiratory System Agents; D012710:Serum Albumin, Bovine; C094049:apaflurane; D005466:Fluorocarbons