Drying Process Optimization for an API Solvate Using Heat Transfer Model of an Agitated Filter Dryer

• Published in: Journal of pharmaceutical sciences Vol. 101; no. 10; pp. 3886 - 3895
• Main Authors: Nere, Nandkishor K., Allen, Kimberley C., Marek, James C., Bordawekar, Shailendra V.
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.10.2012; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: Biological and medical sciences; desolvation; drying; Filtration; Freeze Drying - methods; General pharmacology; Hot Temperature; Kinetics; Medical sciences; mixing; Models, Chemical; Pharmaceutical Preparations - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; solvate; Solvents - chemistry; Technology, Pharmaceutical - methods; solvate; drying; kinetics; mixing; desolvation; Agitation; Heat; Mixing; Pharmaceutical technology; Filter; Process; Kinetics; Optimization; Drying
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23237

Drying an early stage active pharmaceutical ingredient candidate required excessively long cycle times in a pilot plant agitated filter dryer. The key to faster drying is to ensure sufficient heat transfer and minimize mass transfer limitations. Designing the right mixing protocol is of utmost importance to achieve efficient heat transfer. To this order, a composite model was developed for the removal of bound solvent that incorporates models for heat transfer and desolvation kinetics. The proposed heat transfer model differs from previously reported models in two respects: it accounts for the effects of a gas gap between the vessel wall and solids on the overall heat transfer coefficient, and headspace pressure on the mean free path length of the inert gas and thereby on the heat transfer between the vessel wall and the first layer of solids. A computational methodology was developed incorporating the effects of mixing and headspace pressure to simulate the drying profile using a modified model framework within the Dynochem software. A dryer operational protocol was designed based on the desolvation kinetics, thermal stability studies of wet and dry cake, and the understanding gained through model simulations, resulting in a multifold reduction in drying time.