Development of Amlodipine Mini-tablets as a Polypill-component for the Personalized Therapy of Arterial Hypertension

Abstract

Introduction. A personalized choice of antihypertensive combinations and doses is one of the promising trend in the field of combination therapy of arterial hypertension (AH). A polypill as a solid gelatin capsule with combination of mini-tablets can be used to realise this concept. Aim. Development of the composition and technology of Amlodipine 2,5 mg and 5 mg film-coated mini-tablets as a polypill-component for the personalized therapy of AH. Materials and methods. Active pharmaceutical ingredient (API) Amlodipine besylate (Glochem Industries Private Ltd., India) and excipients, such as diluent, disintegrant, lubricant, dye and premix for film coating, were used. Norvasc®, 5 mg tablets were used as a reference drug to estimate the release profile of Amlodipine. API and excipients were mixed in a «drunken barrel» mixer DGN-II (Shanghai Unique Machinery Technology Co., Ltd., China); mini-tablets were obtained on a DP30A laboratory automatic single-punch tablet press (Beijing Gylongli Sci. & Tech. Co., Ltd., China); film coatings on mini-tablets-cores were applied by using a BGB-1 laboratory machine (Chongqing Jinggong Pharmaceutical Machinery Co., Ltd., China). Assessment of technological characteristics of API and tablet mixtures and quality control of mini-tablets were conducted by the methods of State Pharmacopoeia of the Russian Federation XIV ed. Results and discussion. As a result of the study, the optimal composition of the excipients of the fillers group (lactose monohydrate, MCC and anhydrous calcium hydrogen phosphate in a ratio of 1 : 1 : 1) for the production of Amlodipine 2,5 mg and 5 mg mini-tablets-cores by direct compression was established. The technology of applying film coatings was developed. The equivalence of the release profiles of Amlodipine from the developed mini-tablets to the release profile of the reference drug was established. Conclusion. The composition and technology of Amlodipine 2,5 mg and 5 mg film-coated mini-tablets as a polypill-component for the personalized therapy of AH were developed.