Peter O’Connell
Trinity College Dublin, Ireland
Title: Modelling chemical and physical stability of cocrystals. Case study: Sulfadimidine: 4-Amino salycilic acid cocrystal
Biography
Biography: Peter O’Connell
Abstract
Salt formation is a common approach to enhance drug solubility but it is not successful when the API does not contain ionisable functional groups in its chemical structure. Engineering of pharmaceutical cocrystals can be an advantageous strategy to overcome poor drug solubility, without the need to break or create covalent bonds. Predicting the shelf life of solid-dose pharmaceutical products using both stressed and accelerated stability data is often desired in order to avoid long development times and costs, associated with real-time stability testing. However, using an accelerated stability programme, stability data gathered over two to four weeks at elevated temperature and humidity conditions can be used to predict stability at lower temperatures. Modelling of physico-chemical stability of cocrystal systems using an accelerated stability program has not been documented. Statistical estimation of both physical and chemical stability parameters is not straightforward due to the non-linearity of modified versions of the Arrhenius equation. Sulfadimidine (SDM) is a poorly-soluble anti-infective agent. In order to improve its aqueous solubility, several cocrystal habits were formed using a GRAS coformer, 4-aminosalycilic acid (4-ASA). Two different polymorphic forms of the cocrystal were prepared containing equimolar ratios of 4-ASA and SDM. The hypothesis underpinning this work is that cocrystal engineering can be used not only to improve the aqueous solubility of the SDM but also its physicochemical stability by changing the cocrystal habit. A four week accelerated stability approach was used to predict the long term physical and chemical stability of different SDM:4-ASA cocrystals with different polymorphic forms and crystal habits.