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Mahboubeh Razavi,1 Hamed Karimian,1 Chai Hong Yeong,2 Mehran Fadaeinasab,3 Si Lay Khaing,4 Lip Yong Chung,1 Didi Erwandi B Mohamad Haron,5 Mohamed Ibrahim Noordin1,6 1Department of Pharmacy, 2University Malaya Research Imaging Centre and Department of Biomedical Imaging, Faculty of Medicine, 3Center for Natural Product Research and Drug Discovery (CENAR), 4Department of Obstetrics & Gynaecology, 5Shimadzu-UMMC Centre for Xenobiotics Studies, Pharmacology Department, Faculty of Medicine, University of Malaya, 6Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), National Institutes of Biotechnology Malaysia, Ministry of Science, Technology and Innovation, Penang, Malayasia Abstract: This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl), using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP):xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP,3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. 153Sm2O3 was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time (Tmax) at which the maximum concentration of metformin HCl in the blood (Cmax) was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. Cmax and the half-life were found to be within an acceptable range. It is therefore concluded that MKP,3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region.Keywords: drug delivery systems, floating system, gastric retention, sustained release natural polymers, evaluation in vitro and in vivo

Mahboubeh Razavi,1 Hamed Karimian,1 Chai Hong Yeong,2 Lip Yong Chung,1 Shaik Nyamathulla,1 Mohamed Ibrahim Noordin1,3 1Department of Pharmacy, Faculty of Medicine, University of Malaya, 2Department of Biomedical Imaging and University Malaya Research Imaging Centre, Faculty of Medicine, University of Malaya, 3Center for Natural Products and Drug Discovery (CENAR), Department of Chemistry, Faculty of Science, University of Malaya, KualaLumpur, Malaysia Abstract: The present research was aimed at formulating a metformin HCl sustained-release formulation from a combination of polymers, using the wet granulation technique. A total of 16 formulations (F1–F16) were produced using different combinations of the gel-forming polymers: tamarind kernel powder, salep (palmate tubers of Orchis morio), and xanthan. Post-compression studies showed that there were no interactions between the active drug and the polymers. Results of in vitro drug-release studies indicated that the F10 formulation which contained 5 mg of tamarind kernel powder, 33.33 mg of xanthan, and 61.67 mg of salep could sustain a 95% release in 12 hours. The results also showed that F2 had a 55% similarity factor with the commercial formulation (C-ER), and the release kinetics were explained with zero order and Higuchi models. The in vivo study was performed in New Zealand White rabbits by gamma scintigraphy; the F10 formulation was radiolabeledusing samarium (III) oxide (153Sm2O3) to trace transit of the tablets in the gastrointestinal tract. The in vivo data supported the retention of F10 formulation in the gastric region for 12 hours. In conclusion, the use of a combination of polymers in this study helped to develop an optimal gastroretentive drug-delivery system with improved bioavailability, swelling, and floating characteristics. Keywords: gastroretentive drug delivery, gamma scintigraphy, sustain-release study, salep, tamarind seed, xanthan

Mahboubeh Razavi,1 Hamed Karimian,1 Chai Hong Yeong,2 Sazilah Ahmad Sarji,2 Lip Yong Chung,1 Shaik Nyamathulla,1,3 Mohamed Ibrahim Noordin1,31Department of Pharmacy, Faculty of Medicine, 2Department of Biomedical Imaging and University of Malaya Research Imaging Centre, Faculty of Medicine, 3Department of Chemistry, Centre for Natural Products and Drug Discovery (CENAR), Faculty of Science, University of Malaya, Kuala Lumpur,MalaysiaAbstract: The purpose of this study is to evaluate the in vitro and in vivo performance of gastro-retentive matrix tablets having Metformin HCl as model drug and combination of natural polymers. A total of 16 formulations were prepared by a wet granulation method using xanthan, tamarind seed powder, tamarind kernel powder and salep as the gel-forming agents and sodium bicarbonate as a gas-forming agent. All the formulations were evaluated for compendial and non-compendial tests and in vitro study was carried out on a USP-II dissolution apparatus at a paddle speed of 50 rpm. MOX2 formulation, composed of salep and xanthan in the ratio of 4:1 with 96.9% release, was considered as the optimum formulation with more than 90% release in 12 hours and short floating lag time. In vivo study was carried out using gamma scintigraphy in New Zealand White rabbits, optimized formulation was incorporated with 10 mg of 153Sm for labeling MOX2 formulation. The radioactive samarium oxide was used as the marker to trace transit of the tablets in the gastrointestinal tract. The in vivo data also supported retention of MOX2 formulation in the gastric region for 12 hours and were different from the control formulation without a gas and gel forming agent. It was concluded that the prepared floating gastro-retentive matrix tablets had a sustained-release effect in vitro and in vivo, gamma scintigraphy played an important role in locating the oral transit and the drug-release pattern.Keywords: gastro-retentive drug delivery, natural polymer, gamma scintigraphy, sustain release formulation, salep, tamarind seed