Design, development and evaluation of gastroretentive drug delivery system of metformin hcl /
Metformin HCl, a drug from biguanide class, is the most commonly used first-line antihyperglycemic agent in the treatment of NIDDM. The major problems associated with the drug are high dose (1.5-2.0 g/day), frequent dosing due to its shorter biological half-life (1.5-4.9 hr), and low bioavailability...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
Kuala Lumpur:
Kulliyyah of Pharmacy,International Islamic University Malaysia,
2014
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| Subjects: | |
| Online Access: | Click here to view 1st 24 pages of the thesis. Members can view fulltext at the specified PCs in the library. |
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| Summary: | Metformin HCl, a drug from biguanide class, is the most commonly used first-line antihyperglycemic agent in the treatment of NIDDM. The major problems associated with the drug are high dose (1.5-2.0 g/day), frequent dosing due to its shorter biological half-life (1.5-4.9 hr), and low bioavailability (60%). Low bioavailability of metformin results from incomplete absorption of the drug as metformin is majorly absorbed from stomach and lower part of GIT. The study was done for the purpose of developing gastroretentive tablets of metformin HCl to prolong gastric residence time and increase drug bioavailability based on polymer swelling and gas formation. Combination of HPMC and polyethylene oxide was used as both matrix forming agent and swelling agent, while sodium bicarbonate as gas forming agent. Drug-excipient incompatibility was confirmed by DSC and FTIR study. 12 mm circular bi-convex floating tablets were prepared by wet granulation method using a 10-station Rotary tablet press machine. Fabricated tablets were optimized by response surface methodology (RSM) utilizing Box Behnken experimental design. Seventeen (17) trial formulations were investigated taking various compositions of polymer, NaHCO3 and SSG each at three levels. Data analysis and modeling were performed by Design expert® software (version 8.0.7.1, stat-Ease Inc., Minneapolis, MN). The optimized tablets were evaluated for weight variation, hardness, thickness, friability, moisture content, assay, in-vitro floating lag time, % swelling and surface morphology study. Furthermore, optimized tablets were stored at accelerated stability condition (40 °C and 75% RH) for 3 months. All preformulation parameters were found to be within the acceptable range. Melting peaks of metformin was visible in DSC thermogram of drug-excipients mixture, indicating that metformin was compatible with the rest of the excipients of formulation. FTIR study also confirmed the same finding. Floating lag time and duration of floating were found to be dependent on amount of gas effervescent agent (NaHCO3), swelling of polymers (HPMC and PEO) and swelling enhancer (SSG). It was found that formulation with of polymer concentration 250 mg, NaHCO3 60 mg, and SSG 50 mg fulfilled requistes of an optimum formulation. The optimized formulation was found to provide average floating lag time less than 4 minutes with a floating duration of more than 24 hours. Swelling rate of the combination of polymers was found to be rapid and linear for initial 2 hr, however it decreased thereafter and maintained the linearity until 8 hours. Combination of HPMC and PEO allowed efficient control of drug release for 12 hours. SEM figure showed the non-porous nature of tablet outer surface and little bit porous structure of inner surface before dissolution study. However, after dissolution of 2 hours and 8 hours, both surfaces turned into porous structure which allows the drug to diffuse to the surrounding medium. This also proved that the drug release occurs by diffusion. Based on accelerated stability study; optimized formulation was found to be stable for three months without any major changes in assay, dissolution profile, floating lag time and other physical properties. |
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| Physical Description: | xix, 127 leaves : ill. ; 30cm. |
| Bibliography: | Includes bibliographical references (leaves 112-125). |