Development of a Sustained-Release Herbal Tablet using Natural Gums as Binding Agents: Formulation Optimization, Release Kinetics, Statistical Validation, and ICH Stability Assessment

Abstract

One of the ongoing pharmaceutical problems of herbal extracts is developing oral sustained-release (SR) preparations due to the complex phytochemical structure, low water solubility of bioactive markers, and uncontrolled gastrointestinal absorption. The current paper describes the development of the first systematic formulation and optimisation of SR matrix tablets of a standardised Boswellia serrata dry extract (BSE; 65% total boswellic acids) with binary blends of guar gum (GG) and xanthan gum (XG) as natural, biodegradable, hydrophilic matrix-forming binders - without any synthetic polymer adjunct. Wet granulation was utilized to prepare four formulations (F1-F4) with GG:XG mass ratios of 2:1, 3:1, 1:1, and 1:2 and a constant total gum content of 75mg and constant drug load of 200 mg/tablet. Extensive analysis included pre-compression granule characterisation (angle of repose, bulk and tapped density, Carrs index, Hausner ratio, particle size, moisture content), postcompression tablet testing (hardness, friability, thickness, weight uniformity, drug content, swelling index), in vitro drug release during Formulation F3 (GG:XG = 1:1) gave 91.2 ± 2.1% cumulative drug release in 8 hours with unusual non-Fickian release kinetics (Korsmeyer–Peppas r² = 0.9931; n = 0.74). ANOVA proved the statistically significant differences between formulations (F= 18.74; df = 3, 20; p < 0.001) with F3 being significantly better than F1 (Tukey HSD; p < 0.05). The FTIR and DSC analyses indicated the full compatibility of the physicochemical between BSE and the gum excipients. All important quality characteristics of F3 were within the pharmacopoeial specifications of six months of accelerated stability storage. The results confirm the binary GGXG system as a biodegradable, pharmacopoeially acceptable, and cost-effective system to develop SR herbal tablets.