Improving the Filterability and Solid Density of Ranitidine Hydrochloride Form 1

By November 14, 2016Publications

Mahmoud Mirmehrabi et. al.
Journal of Pharmaceutical Sciences, 93 (7), 1692-1700

Ranitidine hydrochloride Form 1 produced by the original method (Price et al., 1978 US patent) has poor filtration and drying characteristics, which make it less desirable commercially in comparison with Form 2. This article shows that the operating parameters have significant influence on the final properties of Form 1. In terms of filterability and solid bulk density, it was found that at a higher temperature (~48°C), the viscosity of the slurry decreased and improved product quality as compared with operating at room temperature (~25°C). It was found that the rapid addition of acid to the ranitidine base increased product density but led to higher residual solvent inclusion. The presence of excess ranitidine base in the solution and also the manner of reactant addition had a significant influence on the onset of nucleation and the rate of crystallization. The best results in terms of filterability and bulk solid density were obtained using an initial pH of 5.3 and then increasing it to 6.3–6.4 after the onset of nucleation.