Formulation development, optimization, in vivo antidiabetic effect and acute toxicity of directly compressible herbal tablets containing Merremia tridentata (L.) extract

The aim of the present study was to design and optimize the oral tablet formulation of Merremia tridentata extract (MSE) with maximum therapeutic effect and acceptable tablet parameters to aid in diabetes treatment using the response surface methodology (RSM) in the direct compression process. The second-order polynomial models of MSE tablet formulation were used to predict the important responses such as in vivo hypoglycemic effect (R² = 0.9794), disintegration time (R² = 0.9939), average percent dissolution (R² = 0.9953), and friability (R² = 0.9867). Research results demonstrated that the optimum formulation of 500 mg MSE tablets with the maximum in vivo hypoglycemic effect (↓69.58% at day 15), maximum dissolution (98.94%), and minimum disintegration time (501s) was found at polyvinyl pyrrolidone K30 of 4.00% wt/wt, croscarmellose sodium of 13.82% wt/wt, and colloidal silicon dioxide of 2.56% wt/wt. Besides, all pre-compression and post-compression parameters of optimal tablet formulation were found to be in the acceptable range of United States Pharmacopeia and Vietnam Pharmacopeia standards in the pilot scale.

Moreover, the MSE tablets of the optimum formulation showed potent in vivo hypoglycemic effects in alloxan-induced diabetic mice with a percentage of 74.32% after 20 days of the treatment. In addition, MSE tablets were shown to significantly improve the plasma lipid profiles at the end of the study. Especially for acute toxicity, MSE tablets do not cause any toxic effects or death, or organ toxicity with LD₅₀ > 30000 mg/kg body weight. In conclusion, the optimal MSE tablets have been successfully formulated by direct compression with a high dosage of herbal extracts and good formulation quality. This study also proved that MSE tablets can be a promising platform to improve the efficacy of diabetes treatment compared to crude MSE and glibenclamide. Moreover, it can be concluded that the RSM is an effective way to develop new MSE tablets within a short period as well as easily scale up for successful commercialization.

Materials

Microcrystalline cellulose (MCC, Avicel PH 102), croscarmellose sodium (CCS), polyvinyl pyrrolidone K30 (PVP K30, Colloidal silicon dioxide (CSD or Aerosil®-200, SiO2), magnesium stearate (Mg St), glibenclamide, and alloxan were all purchased from Sigma-Aldrich (USA). The test kit of hypoglycemic activity (including glucose oxidase, 4-aminophenazone, peroxidase, phenol, phosphate buffer solution pH 7.5, and standard glucose solution 1 mg/mL) was purchased from Merck (Germany).

Em Canh Pham, Lenh Vo Van, Cuong Viet Nguyen, Ngoc Thoi Nguyen Duong, Tuong Vi Le Thi, Formulation development, optimization, in vivo antidiabetic effect and acute toxicity of directly compressible herbal tablets containing Merremia tridentata (L.) extract, Journal of Drug Delivery Science and Technology, Volume 84, 2023, 104445, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2023.104445.

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