Influence of Water on the Solubility of Two Steroid Drugs in Hydrofluoroalkane (HFA) Propellants

Abstract

The objective of this research work was to investigate the influence of water level, temperature, and propellant composition on the solubility of two hydrophobic steroid drugs, triamcinolone acetonide (TAA) and beclomethasone diapropionate (BDP). pMDIs containing TAA or BDP, spiked water, and propellant blend with different ratios of HFA 134a and HFA 227 were prepared. The contents of the prepared pMDIs were filtered through a 0.22 mm Acrodisc, syringe filter into a receiving canister after the pMDIs were equilibrated at 15°C, 25°C, 30°C, and 40°C. The drug concentration in the receiving canisters was determined by HPLC and the drug solubility in the propellant blend was calculated. Also, the drug crystal collected on the filter from the donor pMDIs were characterized by x-ray diffraction. The solubility of TAA and BDP varied with propellant composition at all experimental temperatures investigated. The solubility of TAA and BDP increased as the temperature was increased at all propellant compositions and water levels studied, but decreased as the water level in the propellant system was increased at all compositions and temperatures. The x-ray diffraction results indicated that the water in the propellant system had no significant influence on the crystal characteristics of TAA in HFA propellant system, but had a significant impact on the crystal characteristics of BDP was higher than TAA at all propellant compositions, experimental temperatures and water levels investigated. The solubility of TAA and BDP was not only influenced by propellant composition and storage temperature, but also depended on the water level in the propellant system. As a consequence, the crystallinity of the drugs formulated in HFA propellant was influenced by the temperature, propellant composition and the water level in the propellant system. The impact of these factors on the crystallinity of formulated drugs.