Crystallisation of Beclomethasone Dipropionate from Supersaturated Solutions: The Impact of Solvent Properties on Crystalline APIs
Cordula Weiss1, Peter McLoughlin1, Panagiotis Manesiotis2, Peter Nockemann2 & Helen Cathcart1
1Waterford Institute of Technology, Cork Road, Waterford, X91 K0EK, Ireland
2Queen’s University Belfast, University Road, Belfast, BT7 1NN, Northern Ireland, UK
Beclomethasone dipropionate (BDP) is an inhaled corticosteroid (ICS) with anti-inflammatory properties used to manage patients suffering from asthma or chronic obstructive pulmonary disease (COPD). This active pharmaceutical ingredient (API) is known to form solvates with alcohols and other solvents.
Solvate formation during crystallisation affects material properties and ultimately influences the bioavailability of the API and the efficiency of the finished pharmaceutical product. The impact of using different solvents (acetone, methanol, ethanol, n-propanol, iso-propanol, n-butanol and n-pentanol) to prepare crystalline BDP from supersaturated solution was analysed. It was found that BDP solvates crystallised only from acetone, ethanol, n-propanol and iso-propanol solutions while crystalline BDP prepared from methanol, n-butanol and n-pentanol was in its anhydrous form. Crystals grown in acetone solution appeared to be unstable with irregular features and non-reproducible characteristics.
The crystalline structure – solvated or anhydrous forms – of the API was confirmed using a novel approach which combining nuclear magnetic resonance (NMR) spectroscopy with single crystal X-ray diffraction (XRD). The interactions between solvent and BDP molecules were analysed.
This method is a valuable tool for assessing solvate formation through crystallisation from supersaturated solutions and can be used to analyse the mobility and preferred position of solvent molecules within the solvates.