title: Cost-Effective Isolation of a Process Impurity of Pregabalin.
abstract: Cost-effective isolation methods were developed on preparative HPLC, flash LC, and simulated moving bed (SMB) to prepare the process impurity, 3-(aminomethyl)-5-methylhex-4-enoic acid (4-ene impurity), of pregabalin. By a thorough experimental study on the different isolation techniques available, it was concluded that SMB was the most cost-effective. Hence, it was a continuous chromatography that utilized the advantage of SMB so that a high quantity of the impurity was generated in a short period of time. SMB was equipped with eight reversed-phased columns and was used to separate the process impurity of pregabalin. The effects of flow rate in zone 2 (Q2) and 3 (Q3), as well as switching time, on the operating performance parameters like purity, productivity, and desorbent consumption were studied. Operating conditions leading to more than 90% purity in the raffinate outlet stream were identified, together with those achieving optimal performance. All of these developed methods are novel, cost-effective, and can be applied to the isolation of other process- and stability-related impurities of pregabalin.
authors.affiliation: Department of Analytical Research and Development, Dr. Reddy's, Laboratories Ltd, IPDO, Hyderabad, 500072, Telangana, India; Pharmaceutical Chemistry Division, School of Advanced Sciences, VIT University Vellore-632014, TN, India.
authors.forename: Lakkireddy
authors.initials: L
authors.lastname: Prakash
authors.affiliation: Pharmaceutical Chemistry Division, School of Advanced Sciences, VIT University Vellore-632014, TN, India.
authors.forename: Malipeddi
authors.initials: M
authors.lastname: Himaja
authors.affiliation: Department of Analytical Research and Development, Dr. Reddy's, Laboratories Ltd, IPDO, Hyderabad, 500072, Telangana, India.
authors.forename: Belly
authors.initials: B
authors.lastname: Ramakrishna Yadav
authors.affiliation: Department of Analytical Research and Development, Dr. Reddy's, Laboratories Ltd, IPDO, Hyderabad, 500072, Telangana, India.
authors.forename: Arumalla
authors.initials: A
authors.lastname: Maheshwara Reddy
keywords: Flash chromatography; Impurity; Isolation; Pregabalin; Preparative HPLC; Simulating moving bed
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