STUDY ON FORMULATION, CHARACTERIZATION AND MODIFICATION OF SUSTAINED RELEASE BILAYER MATRIX TABLETS OF PROPRANOLOL HCl AND NIFEDIPINE FOR ANTIHYPERTENSIVE THERAPY

Background: Sustained-release (SR) bilayer matrix tablets allow two release segments, or two drugs, to be combined in one dosage unit. Propranolol hydrochloride (BCS class I) and nifedipine (BCS class II) are complementary antihypertensives, but their contrasting solubility makes the design of a shared SR system challenging. Objective: To critically analyse published formulation, characterization and modification data on SR bilayer/matrix tablets of propranolol HCl and SR hydroxypropyl methylcellulose (HPMC) tablets of nifedipine, and to derive an evidence-based design framework for a combined bilayer tablet. Methods: Quantitative data on composition, micromeritics, tablet quality, drug release, swelling, release kinetics, particle size, similarity factor (f2) and bioequivalence were extracted from five key studies. Published dissolution data (HPMC K15M and Kollidon® SR matrices, 1–4 h) were re-analysed using zero-order, first-order, Higuchi, HixsonCrowell and Korsmeyer–Peppas models, and Hausner ratios were derived from reported compressibility indices. Results: In the bilayer propranolol tablet, 20 mg sodium starch glycolate released 99.72% of the loading dose in 10 min, while the SR layer containing 40% HPMC K15M (F9) released 98.41% over 12 h (f2 = 60.5; Peppas n = 0.622; anomalous transport). Re-analysis showed that release from low-polymer matrices was best described by the Higuchi model (R2 ≥ 0.989), whereas higher Kollidon® SR levels gave near-linear release (zero-order R2 = 0.998–0.999). For nifedipine, raw-drug particle size governed release similarity: the batch whose in-tablet D90 (147 µm) matched the reference (150 µm) gave f2 = 78.2 and was bioequivalent under fasting and fed conditions. Conclusion: Polymer grade and level control the propranolol layer, while particle size and solubilisation control the nifedipine layer. A proposed propranolol–nifedipine bilayer composition and a characterization protocol are presented for experimental verification.