Design and Evaluation of A Sustained-Release Polyherbal Antidiabetic Formulation

Design and Evaluation of A Sustained-Release Polyherbal Antidiabetic Formulation Himank Varshney 1Sahu Onkar Saran School of Pharmacy, Faculty of Pharmacy, IFTM University Moradabad, U.P. India https://orcid.org/0009-0005-9527-7575 Sadhna Solanki 2Department of Pharmacy Practice, Teerthanker Mahaveer University, TeerthankerMahaveer College of Pharmacy, Moradabad (UP), India Jyotirmoy Bhattacharyya 3Faculty of Pharmaceutical science, Assam down town University, Panikhaiti, Guwahati, Assam, India https://orcid.org/0000-0003-0953-2874 E. Joel Mart 4Department of Pharmacology, Vels Institute of Science, Technology and Advanced Studies (VISTAS), PV Vaithiyalingam Rd, Velan Nagar, Krishnapuram, Pallavaram, Chennai, Tamil Nadu, India https://orcid.org/0009-0000-9560-674X Mohamed Fahid.H 5,Vels Institute of Science, Technology and Advanced Studies (VISTAS) PV Vaithiyalingam Rd, Velan Nagar, Krishnapuram, Pallavaram, Chennai, Tamil Nadu India https://orcid.org/0009-0003-5795-8826 Mugesh. K 5,Vels Institute of Science, Technology and Advanced Studies (VISTAS) PV Vaithiyalingam Rd, Velan Nagar, Krishnapuram, Pallavaram, Chennai, Tamil Nadu India https://orcid.org/0000-0003-3913-691X Mohamed Yaasir.H 6Lachoo Memorial College of science and technology (Automous), Pharmacy wing, Jodhpur Rajasthan, India https://orcid.org/0009-0004-7852-6472 Anil Pareek 6Lachoo Memorial College of science and technology (Automous), Pharmacy wing, Jodhpur Rajasthan, India https://orcid.org/0000-0001-8837-3765 D. Akiladevi 7Department of Pharmaceutics, School of Pharmaceutical Sciences, Vels Institute of Science Technology and Advanced studies, Pallavaram, Chennai, India

The aim of this study was to prepare, optimize, and test sustained release matrix tablet formulation of hydroalcoholic extracts of Alstoniascholaris, Centellaasiatica, Corchorustrilocularis and Morindapubescens to enhance antidiabetic treatment. Procedures: Soxhlet extraction (ethanol:water, 70:30 v/v) was used to extract plant materials. Phytochemical screening and quantitative estimation (total phenolics, flavonoids, gallic acid, quercetin) were performed. FTIR and DSC were used in compatibility studies. HPMC K15M was used to prepare matrix tablets with a rate-controlling polymer through the 3 2 factorial design. The parameters of pre-compression (bulk/tapped density, Carr index, Hausner ratio, angle of repose) and post-compression (weight variation, hardness, friability, drug content, disintegration) were measured. Releases were tested in vitro in phosphate buffer, pH 6.8 over 24 hours and kinetic modeling (zero-order, first-order, Higuchi, Korsmeyer-Peppas, Hixson-Crowell) was done. ICH-based accelerated stability testing was done. The effects of streptozotocin-induced diabetic Wistar rats on in vivo antidiabetic activity were evaluated in 28 days, which included antioxidant parameters and histopathology. Outputs: Extraction was 14.6 w/w. The optimized formulation (F6: 30% HPMC K15M) had good pre-compression properties (Carrs index 14.3, angle of repose 28.4deg) and post-compression homogeneity (hardness 6.8+0.4 kg/cm 2, friability 0.48, drug content 97.2-101.5 Cumulative release of the in vitro release was 91.4% cumulative after 24 hours, exhibiting Higuchi kinetics (R 2=0.989) with anomalous (non-Fickian) diffusion (n=0.61). Rapid stability testing showed that flavonoid retention was 94.2% after six months. In vivo, the formulation considerably decreased the fasting blood glucose of 286±12 to 124±9 mg/dL (p<0.001) in comparison to metformin (118±8 mg/dL), and better sustained effect than unformulated extract (148±11 mg/dL). The level of antioxidant enzymes (GSH, SOD, catalase) was significantly recovered, and MDA was decreased. There was moderate pancreatic islet regeneration as seen by histopathology. Summary: The HPMC-derived sustained-release polyherbal matrix pill was effectively able to attain 24-h controlled release, increased in vivo antidiabetic activity, improved stability and exhibited good compatibility. This combination is a promising, patient-adherent alternative to traditional therapy, and a bridge between traditional polyherbalism and the current pharmaceutical technology.
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