Design and Development of Clopidogrel Bisulfate Gastroretentive Osmotic Formulation Using Quality by Design Tools

• Published in: AAPS PharmSciTech Vol. 18; no. 7; pp. 2626 - 2638
• Main Authors: Desai, Nilesh, Purohit, Ravindra
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2017
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Pharmacology/Toxicology; Pharmacy; Research Article; quality by design; clopidogrel bisulfate; design of experiment; gastroretentive osmotic tablet
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-017-0731-3

Clopidogrel bisulfate (CBS) is antiplatelet drug and it is becoming a drug of choice in the treatment and management of prevention of heart attacks and strokes. CBS is stable and soluble in acidic pH; therefore, retention in stomach for prolonged period appears to be beneficial for controlling the bioavailability. The gastroretentive osmotic system (GROS) facilitates prolonged retention of drug in stomach and provides zero-order drug release. A complex formulation like GROS poses many challenges, and QbD tools can help in designing robust formulation which takes all aspects of product and process development in order to deliver a robust product. The GROS was formulated in three steps: core tablet, osmotic tablet, and gastroretentive osmotic tablet. The design of experiment was used for screening and optimization of formulation and process-related parameters. The dissolution study was carried out to analyze the release pattern of tablet. The optimized batch O-4 showed cumulative drug release of 19.43, 30.49, 64.41, and 85.11% at 2, 4, 8, and 12 h which is in the range of QTPP predictions. The novel technique of GROS was implemented successfully which demonstrates robust design giving consistent and desired results.