Related Experiment Videos
Improving the filterability and solid density of ranitidine hydrochloride Form 1
Mahmoud Mirmehrabi1, Sohrab Rohani, K S Keshava Murthy
1Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, Ontario, N6A 5B9, Canada.
Journal of Pharmaceutical Sciences
|June 4, 2004
Summary
Optimizing ranitidine hydrochloride Form 1 production involves controlling operating parameters. Higher temperatures and specific pH adjustments significantly improve filtration and drying characteristics for better commercial viability.
Area of Science:
- Pharmaceutical Sciences
- Chemical Engineering
Background:
- Ranitidine hydrochloride Form 1 exhibits poor filtration and drying properties, limiting its commercial appeal compared to Form 2.
- The original production method (Price et al., 1978 US patent) requires optimization for improved physical characteristics.
Purpose of the Study:
- To investigate the impact of operating parameters on the physical properties of ranitidine hydrochloride Form 1.
- To identify optimal conditions for enhancing filterability and bulk density of Form 1.
Main Methods:
- Systematic variation of operating parameters including temperature, acid addition rate, and reactant addition.
- Monitoring of slurry viscosity, product density, residual solvent inclusion, nucleation onset, and crystallization rate.
- Evaluation of filterability and bulk solid density under different process conditions.
Main Results:
- Operating at approximately 48°C, compared to room temperature (25°C), decreased slurry viscosity and improved product quality.
- Rapid acid addition increased product density but also residual solvent inclusion.
- An initial pH of 5.3, followed by an increase to 6.3-6.4 post-nucleation, yielded the best filterability and bulk density.
Conclusions:
- Operating parameters critically influence the final properties of ranitidine hydrochloride Form 1.
- Controlled temperature and pH adjustments are key to enhancing the filterability and bulk density of Form 1.
- Optimized production can improve the commercial desirability of ranitidine hydrochloride Form 1.