Reformulation of Stmerin® D CFC formulation using HFA propellants

• Published in: Pharmaceutical development and technology 2013-11, Vol.18 (6), p.1314-1318
• Main Authors: Murata, Saburo, Izumi, Takashi, Ito, Hideki
• Format: Article
• Language: English
• Subjects: actuator; Administration, Inhalation; Chemistry, Pharmaceutical - methods; Chlorofluorocarbons - chemistry; Chlorofluorocarbons, Ethane - chemistry; Chlorofluorocarbons, Methane - chemistry; Drug Stability; Hydrocarbons, Fluorinated - chemistry; hydrofluoroalkane (HFA) propellant; Metered dose inhaler (MDI); middle chain fatty acid triglyceride (MCT); Particle Size; Solubility; Solvents - chemistry; Suspensions - chemistry
• ISSN: 1083-7450; 1097-9867
• DOI: 10.3109/10837450.2012.680596

Stmerin® D was reformulated using hydrofluoroalkanes (HFA-134a and HFA-227) as alternative propellants instead of chlorofluorocarbons (CFCs), where the active ingredients were suspended in mixed CFCs (CFC-11/CFC-12/CFC-114). Here, we report the suspension stability and spray performance of the original CFC formulation and a reformulation using HFAs. We prepared metered dose inhalers (MDI) using HFAs with different surfactants and co-solvents, and investigated the effect on suspension stability by visual testing. We found that the drug suspension stability was poor in both HFAs, but was improved, particularly for HFA-227, by adding a middle chain fatty acid triglycerides (MCT) to the formulation. However, the vapor pressure of HFA-227 is higher than a CFC mixture and this increased the fine particle dose (FPD). Spray performance was adjusted by altering the actuator configuration, and the performance of different actuators was tested by cascade impaction. We found the spray performance could be controlled by the configuration of the actuator. A spray performance comparable to the original formulation was obtained with a 0.8 mm orifice diameter and a 90° cone angle. These results demonstrate that the reformulation of Stmerin® D using HFA-227 is feasible, by using MCT as a suspending agent and modifying the actuator configuration.