The Performance of Opt2Fill® Propellant Dispersible Tablet pMDI Formulations of Salbutamol Sulphate and Salbutamol Sulphate with Beclometasone Dipropionate in HFA 134a and HFA 152a

Simon Warren, Cuong Tran, Chen Zheng, & Glyn Taylor

i2c Pharma Services, Cardiff Medicentre, Cardiff, CF14 4UJ, UK.

Summary

Opt2Fill® tablets are novel propellant dispersible tablets for the manufacture of pressurised metered dose inhalers (pMDIs).  This study has investigated salbutamol sulphate (SS) formulated as Opt2Fill tablets using inhalation lactose and menthol as excipients.  The SS Opt2Fill tablet pMDI formulations were evaluated in two propellants, HFA 134a and HFA 152a.  A combination formulation of SS with beclometasone dipropionate (SS/BDP) in Opt2Fill tablets was also investigated using HFA 134a and HFA 152a which also contained ethanol to ensure that the BDP was in solution.  HFA 152a has a global warming potential that is approximately 10-fold less than HFA 134a and thus, in the light of increasing environmental regulation of fluorine containing gases, is being considered as an alternative propellant.  Next Generation Impactor data showed that high quality aerosols, with fine particle fractions (FPF’s, %< 5.0 µm, emitted dose) for SS and BDP in excess of 60% can be generated from both SS and SS/BDP Opt2Fill tablet pMDI formulations using either HFA 134a or HFA 152a as propellant.  The FPF’s are significantly higher than the currently marketed SS products, Ventolin® and Airomir® and not inferior to the BDP marketed product, QVAR® 50.  Differences in the physical properties of HFA 134a and 152a did not significantly influence aerosol performance in terms of FPF or mass median aerodynamic diameter (MMAD) for the Opt2Fill SS formulations.  There were however some small but statistically significant differences in the FPF and MMAD of Opt2Fill SS/BDP formulations in HFA 134a and HFA 152a containing ethanol.