ABSTRACT
Aims: Metformin Hydrochloride, a biguanide, is an orally active antihyperglycemic agent, used in the treatment of non-insulin dependent diabetes mellitus (NIDDM). It has relatively short plasma half life, low absolute bioavailability. Extended release formulation of Metformin Hydrochloride by direct compression method has significant challenges due to its poor inherent compressibility and high dose. The aim of this study was to develop extended release tablets of Metformin Hydrochloride by direct compression method and In vitro evaluation. Study Design: Nine different formulations were made by varying drug-polymer ratio and were subjected to different physical property tests of the powder blend as well as prepared tablets, followed by dissolution test. Place and Duration of Study: Department of Pharmacy, State University of Bangladesh, Dhaka, Bangladesh, between January 2013 and July 2013. Methodology: Nine formulations of Metformin Hydrochloride matrix tablets - F-1, F-2, F- 3, F-4, F-5, F-6, F-7, F-8 and F-9 - were prepared by direct compression method using release retarding materials, Methocel K100 MCR Premium (derivative of hydroxypropyl methylcellulose - HPMC) and Xanthan gum. The drug and polymer ratio were 1:0.41, 1:0.45, 1:0.49, 1:0.59, 1:0.63, 1:0.67, 1:0.77, 1:0.81 & 1:0.85 respectively. The micromeritic behavior of the powder blends were evaluated for bulk density, angle of repose, compressibility index along with post compressional attributes of the tablets such as thickness, hardness, friability, weight variation and content of Metformin Hydrochloride in the tablets. The in-vitro drug release study was carried out in 1000 mL phosphate buffer medium (pH 6.8) at 37±0.5°C at 100 rpm for 10 hours using USP Apparatus Type-II (paddle) method. Results: FT-IR study showed drug-excipient compatibility and DSC analysis showed no solid state interaction between components. The physical properties of the powder blend and the tablets were within the acceptable limits. Maximum and minimum drug release were found in formulation F-1 and F-9 respectively which indicate that release rate is inversely proportional to the concentration of Methocel K100 MCR Premium and Xanthan gum in combination. Dissolution study also showed that, formulations F-7, F-8 & F-9 do not comply with drug release specification of USP and among the rest six formulations F- 3, F-4 & F-5 comply better with drug release specification of USP. After fitting the data to Korsmeyer-Peppas equation we found that diffusion along with erosion could be the mechanism of drug release.Considering the micromeritic behaviour of the powder blend, physical attributes of the compressed tablets, and dissolution, formulation F-4 seemed most suitable. Conclusion: Extended release Metformin Hydrochloride tablets can be produced to overcome frequent dosing related problems. However, Further study on formulation optimization and scale up, stability and bioequivalence is needed to confirm the appropriateness of these formulated extended release tablets.
ABSTRACT
Aims: To study and evaluate In vitro antioxidant, brine shrimp lethality and antimicrobial activities of both methanol and ethyl-acetate extracts of Citrus macroptera Montr. Fruit (Family-Rutaceae). Study Design: In vitro antioxidant, brine shrimp lethality and antimicrobial activities. Place and Duration of Study: Department of Pharmacy, Jahangirnagar University, Savar, Dhaka-1342. The study was carried out from November 2013 to January 2014. Methodology: In vitro antioxidant activities of the extracts were studied using DPPH radical scavenging assay, NO scavenging assay, total phenol, total flavonoid content, total antioxidant capacity, total tannin content, lipid peroxidation by TBA, lipid peroxidation in human erythrocyte cell, reducing power capacity and cupric reducing capacity assays. Lethality bioassay was performed on Artemia salina Leach nauplii. Antimicrobial activity was investigated by disc diffusion technique. Results: Methanol extract showed better activity than ethyl acetate extract in DPPH, NO, lipid peroxidation by TBA, reducing power capacity assay, total phenol, total flavonoid and total antioxidant capacity assays while ethyl –acetate extract showed more potency than methanol extract in total tannin content, cupric reducing capacity and lipid peroxidation in human erythrocyte assays. In brine shrimp bioassay both extracts showed promising lethal activity but methanol extract was found to be more potent than ethyl acetate extract (χ2=39.874, P<0.0001). In disc diffusion technique among six bacterial species, ethyl acetate extract showed broad spectrum antimicrobial activity against two gram positive Bacillus sublitis and Staphylococcus aureus and one gram negative Escherichia coli. Conclusion: The results demonstrate that methanol and ethyl-acetate extracts of C. macroptera fruit can be used as potential antioxidant, cytotoxic and antimicrobial agents. That is why extensive researches are necessary to search for active principles responsible for these activities.