Impact of mixed counter ion on saturation solubility of esylate salt of a weak basic drug to formulate physically stable and non-hemolytic ready to use injectable solution

Publication date: Available online 9 November 2019Source: International Journal of PharmaceuticsAuthor(s): Gautam Dalwadi, Yan Sun, Lihong Wang, Jordan Shick, Kaitlin Hicks, Stephanie Lam, Vinod Tuliani, Kamlesh PatelAbstractCurrent work investigates a typical issue in formulating a physically stable solution especially when more than one counter ions exist in the composition. The impact of different counter ions on solubilization of an esylate salt of GSK-497, [BH+-CH3SO-3H2O] (1:1) and free base (pKa value 8.0) was investigated to formulate ready to use small volume injectable solution. The concentration dependent aggregation was also appeared to be responsible for hemolytic nature of the drug, therefore a careful investigation was needed to select appropriate counter ion solution without compromising solubilization and leading into higher order aggregation. The esylate salt’s native pH in water was closer to pHmax, thus it was risky to render the solution unbuffered. Generally, it is recommended to formulate at least two pH unit away from pHmax to prevent disproportionation related physical instability, this was achieved by buffering solution away from pHmax, using a lactate counter ion (other than esylate salt of API salt) that did not compromise solubility of the given phase and did not appear to promote higher order of aggregation. The rationale for selecting second counter ion was primarily based on the comparison of esylate salt’s solubility product (Ksp), with th...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research