Formulation Development, Process Optimization, and Quality Assessment of Amlodipine Besylate 5 Mg Tablets for Regulatory Submission
Abstract
Amlodipine besylate is a long-acting calcium channel blocker widely used for hypertension and angina, for which 5 mg amlodipine base is a standard dose; however, moisture sensitivity and excipient-mediated degradation can complicate development of pharmaceutically equivalent generic tablets intended for regulatory submission. This work aimed to develop, optimize, and quality-characterize an Amlodipine Besylate 5 mg tablet aligned with technical dossier expectations, with explicit excipient justification and stability assurance. To deliver 5 mg amlodipine base, tablets were formulated with 6.93 mg amlodipine besylate and manufactured by direct compression to reduce moisture exposure. The active substance was identified by UV spectrophotometry and open-capillary melting point. A lactose-free formulation strategy was implemented to avoid lactose–magnesium stearate interaction pathways associated with glycosyl degradation products; microcrystalline cellulose and anhydrous dibasic calcium phosphate were used as diluents/binders, sodium starch glycolate as super-disintegrant, and magnesium stearate as lubricant. Process optimization included Co-mill speeds of 1700–1900 RPM (optimized at ~1800 RPM), controlled sifting (#60 for API and sodium starch glycolate; #40 for diluents/lubricant), blending for 15 min, lubrication for 3 min, and compression. Optimized pilot batches met pharmacopoeial quality targets, including weight uniformity within ±7.5%, hardness >3.0 kg/cm², friability <1.0%, disintegration <10 min, and dissolution >80% in 30 min (exceeding the ≥75% criterion). Assay by stability-indicating HPLC-UV (C18, 237 nm) showed 98.5–101.3% across three batches, within the 90–110% specification. Forced degradation under acid/alkali hydrolysis and oxidation supported formulation stability without emergence of glycosyl impurities, and process capability evaluations indicated robust, reproducible milling and blending. Overall, the lactose-free direct-compression product provides a compliant quality package suitable for Module 3 dossier compilation and supports stable, equivalent tablet manufacture for approval.
Keywords: Amlodipine besylate, Direct compression, Stability-indicating, Process optimization, Regulatory submission, Dossier
Keywords:
Amlodipine besylate, Stability-indicating, Process optimization, Regulatory submission, DossierDOI
https://doi.org/10.22270/jddt.v16i8.7925References
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