DEVELOPMENT OF HPMC-BASED MATRIX TABLETS FOR THE SUSTAINED RELEASE OF METFORMIN HYDROCHLORIDE

*Akshay Kumar Sinha, Prof. Dr. Pankaj Kumar Sharma, Prof. Dr. Jaya Sharma, Prof. Ms. Priyanka Singh Rajora

ABSTRACT

537 million individuals globally are affected by type 2 diabetes mellitus (T2DM) India has the highest number of cancer cases worldwide. Metformin Hydrochloride is classified as a biguanide of BCS Class III. It is the first oral agent used to treat diabetes. Side-effects of this drug are dose-dependent. Also, it has a short elimination half-life (4-9 h), and thus, requires repeated dosing (2-3 times daily). The present investigation was planned and evaluated the sustained release matrices tablets of Metformin HCl (500mg) using natural polymers (Xanthan Gum, Guar Gum) and synthetic polymers (HPMC K15M, HPMC K100M) alone or in combinations for a period of 12 hr release. Through direct compression, twenty-seven formulations were created using a 3.2 full factorial design. The optimized formulation was also made using wet granulation. The pre-formulation studies including FTIR, DSC, solubility and powder flow and the post compression parameters including weight variation, hardness, friability, drug content, swelling index, erosion index and in vitro dissolution were done as per IP 2022/ USP 46. Dissolution profile comparison was performed with the marketed formulation, Glycomet SR 500 mg, by similarity factor (f2). The optimized natural-polymer formulations F5 (22.5% Xanthan Gum + 17.5% Guar Gum) with 12 hours 87.6% drug release having f2 = 58.4 versus reference comply with the pharmacopoeial acceptance (f2 ≥ 50). The abnormal dispersion pattern of drug release follows the Korsmeyer power law. The performance of S5 synthetic polymer formulation (HPMC K100M 22.5%/K15M 17.5%) was similar (f2 = 61.4). The hardness (7.4 – 8.8 kp), friability (0.22 – 0.68 %), weight variation (<3%) and drug content (98.4 – 101.8 %) of all formulations were as per official limits. According to the study, matrices based on natural gums have the potential to be used in place of HPMC-based matrices to design once-daily sustained-release dosage forms of high-dose high water-soluble drug.

Keywords: Metformin Hydrochloride; Sustained-release matrix tablet; HPMC; Xanthan Gum; Guar Gum; Similarity factor (f2); Korsmeyer–Peppas model; Type 2 Diabetes Mellitus.