Formulation and evaluation of floating matrix tablets of metformin using acrylate methacrylate copolymer and <i>Irvingia gabonesis</i> gum

Abstract

The aim of this study was to formulate metformin as a floating drug delivery system using Irvingia gabonesis gum in order to increase its bioavailability and enhance its site-specific absorption. Floating matrix granules of metformin were prepared by wet granulation technique using the extracted natural gum from Irvingia gabonensis at varying concentrations (2, 4, 6 and 8 %w/w). Sodium bicarbonate (30%) and tartaric acid (5%) were incorporated as the gas generating agents. Formulations were either prepared alone with the natural gum or with the addition of 1.0 %w/w of acrylatemethacrylate copolymer (Eudragit RL100). All granules were evaluated for micromeritic properties i.e. bulk and tapped densities, Hausner’s ratio, Carr’s index, and angle of repose. Granules were compressed at an optimized compression pressure of 35 arbitrary unit on the tableting machine load scale. Tablets were evaluated for hardness, friability, floating lag time, in vitro buoyancy and drug release profiles. Release data were subjected to analysis by four different mathematical models namely, – zero order flux, first order, Higuchi square root of time relationship and Korsmeyer-Peppas equation. Drug-excipient compatibility study was done using Fourier Transform Infra-red Spectroscopy (FTIR). From the results obtained, all formulated gastroretentive floating matrix (GRFM) granules were free flowing with angle of repose and Carr’s index ≤ 30.2º and ≤ 11% respectively. The floating lag time for GRFM tablets formulated with Irvingia gabonesis was ≤ 850 s. The in vitro buoyancy times of GRFM tablets formulations using Irvingia gabonesis gum alone (i.e. without the incorporation of acrylatemethacrylate copolymer) were <12 h while those formulations with the incorporation of acrylatemethacrylate copolymer were >12 h. All GRFM granules were compressible with tablet hardness between 2.2 – 6.3 Kpa. There was a significant difference in tablet hardness with increase in binder concentration (p<0.05). Generally, GRFM tablet percentage friability decreased with increase in binder concentration (≤ 0.98%). The % maximum release (m∞) and time to achieve it i.e. (t∞) for all GRFMTs were ≥78% and ≥4 h respectively. All the formulations with Irvingia gabonesis gum fitted well into Higuchi model release kinetics except for formulations IG4 and IG5. Release exponents (n) for all the formulations had values > 0.45, hence their release mechanism was by Non-Fickian diffusion. FTIR studies show that the excipients and the active pharmaceutical ingredient (API) i.e. metformin were compatible. Irvingia gabonesis gum has been investigated in the formulation of gastroretentive floating matrix tablets of metformin which may find useful application in sustained release drug delivery particularly for drugs with short biological half-life that require frequent administration.

Keywords: Floating drug delivery system (FDDS), Irvingia gabonesis gum, Metformin hydrochloride, Gastroretentive floating matrix tablets (GRFMTs).