Development And Evaluation of A Telmisartan Immediate-Release and Metformin Hydrochloride Sustained-Release Multiparticulate Tablet Using Fluidized-Bed Pelletization

Abstract

Background: Hypertension and type 2 diabetes mellitus frequently coexist, creating a need for dosage forms capable of delivering antihypertensive and antihyperglycemic therapy in a coordinated manner. Multiparticulate systems prepared by fluidized-bed processing provide an approach for combining immediate-release and modified-release components in a single oral dosage form. Objective: To develop and preliminarily evaluate a tablet containing immediate-release Telmisartan and sustained-release Metformin hydrochloride using fluidized-bed drug layering and polymer coating.

Methods: Metformin hydrochloride was layered onto sugar spheres and subsequently coated with HPMC K4M/PVP K30-based release-retarding systems to obtain sustained-release pellets. Telmisartan was incorporated into an immediate-release granule fraction. Five formulations (F1–F5) were prepared and compressed with the sustained-release pellets, Telmisartan, lactose, talc, magnesium stearate and parabens. Powder-flow properties, tablet physical characteristics, disintegration and in-vitro dissolution were evaluated.

Results: Pre-compression batches showed bulk density of 0.421–0.476 g/mL, tapped density of 0.442–0.521 g/mL, Carr’s index of 3.61–9.26%, Hausner’s ratio of 1.03–1.19 and angle of repose of 22.37–28.78°. Tablet hardness was 5.41–5.88 kg/cm² and friability was 0.24–0.61%. Telmisartan immediate-release disintegration times ranged from 5.31 to 7.01 min. Metformin release at 12 h was 95.76%, 97.06%, 99.70%, 99.04% and 96.44% for F1–F5, respectively.

Conclusion: Fluidized-bed palletization successfully generated a multiparticulate tablet exhibiting rapid disintegration of the immediate-release component and extended release of Metformin hydrochloride for up to 12h under the reported in-vitro conditions.