Formulation and Evaluation of Sustained Release Matrix Tablets Using Natural Rate-Controlling Polymer

Abstract

Background: Metformin Hydrochloride (HCl), the first-line pharmacological agent for Type 2 Diabetes Mellitus(T2DM), is classified as a BCS Class III drug with high aqueous solubility but poor intestinal permeability, oralbioavailability of 50–60%, and a narrow upper gastrointestinal absorption window mediated by saturable organic cationtransporter 1 (OCT1). Conventional immediate-release tablets necessitate thrice-daily dosing, resulting in pronouncedpeak-and-trough plasma fluctuations, gastrointestinal adverse events, and suboptimal patient compliance.

Objective: To develop and evaluate sustained release (SR) hydrophilic matrix tablets of Metformin HCl using isolatedFenugreek seed mucilage (Trigonella foenum-graecum) at varying concentrations (10–40% w/w), and to identify theoptimized formulation achieving target release of ≤30% at 1 h and ≥80% at 12 h.

Methods: Fenugreek seed mucilage was extracted by aqueous boiling and acetone precipitation and characterized forphysicochemical and micromeritic properties. Four tablet batches (F1–F4) were prepared by wet granulation withmucilage concentrations of 10%, 20%, 30%, and 40% w/w. Tablets were evaluated for preformulation compatibility(FTIR, DSC), pre-compression flow properties, post-compression pharmacopoeial parameters, in vitro swelling index, invitro drug release (USP Type II, phosphate buffer pH 6.8, 12 h), drug release kinetic modeling, and accelerated stabilitytesting (40°C/75% RH, 3 months, ICH Q1A(R2)).

Results: FTIR and DSC confirmed physicochemical compatibility between Metformin HCl and all excipients.Calibration curve in phosphate buffer pH 6.8 (λmax 233 nm) was linear over 2–20 µg/mL (y = 0.0412x + 0.0028, R² =0.9996). All batches complied with pharmacopoeial quality tests: hardness 5.4–6.6 kg/cm², friability 0.32–0.68%, drugcontent 98.2–100.4%. Batch F4 (40% w/w mucilage) was the optimized formulation, exhibiting maximum swelling indexof 508.3 ± 7.2% at 12 h, drug release of 19.8% at 1 h and 85.2% at 12 h, and anomalous non-Fickian transport(Korsmeyer–Peppas n = 0.62, R² = 0.999). Accelerated stability confirmed drug content of 98.7 ± 1.0% and unchangeddissolution profile (f₂ ≥ 50) over three months.

Conclusion: Fenugreek seed mucilage at 40% w/w functions as an effective, biodegradable, and economically viablenatural polymer for developing once-daily SR matrix tablets of Metformin HCl, offering a promising green alternative tosynthetic polymers such as HPMC for high-dose BCS Class III formulations.

Keywords: Metformin Hydrochloride, sustained release, fenugreek seed mucilage, galactomannan, hydrophilic matrixtablet, wet granulation, Korsmeyer–Peppas, anomalous transport, natural polymer, BCS Class III.