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    • Bachelor of Pharmacy
    • Project report (Bachelor of Pharmacy)
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    In-vitro preformulation studies for the development of a novel antidiabetic combination therapy involving linagliptin and dextromethorphan

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    Date
    2018-01
    Publisher
    BRAC Univeristy
    Author
    Shishir, Tushar Ahmed
    Metadata
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    URI
    http://hdl.handle.net/10361/10314
    Abstract
    Hyperglycemia and decreased insulin secretion and its less sensitivity seems to be the primary defects associated with diabetes and available treatments focus on reducing those defects. Sulfonylureas and metformin were the first line treatment for type 2 diabetes mellitus despite knowing their progressive action towards beta cell damage and within 3 years of their use, 50% beta cells failure take place and patients require additional pharmacological agents to control type 2 diabetes. A new method of treatment is to target the incretin mimetic hormones, which are secreted by intestinal cells in response to food intake, provoking glucose-dependent insulin secretion from the pancreas. Gliptins are the agents, which improve beta cells health and suppress glucagon, resulting in improved post-prandial and fasting glucose by preventing the metabolism of incretin hormones by DPP-4 enzymes. Among gliptins, Linagliptin is considered as the most potent because of its improvements of HbA1c level as well as efficacy, safety and least incidence of hypoglycemia, which makes it a unique drug. In addition, recent study found that, NMDARs antagonist dextromethorphan increase the postprandial insulin secretion from beta cells by depolarizing the cell membranes of beta cells in the pancreas. The research suggests, gliptins in combination with dextromethorphan improves both postprandial and fasting glucose level of diabetes patients as well as keeps the HbA1c level below 7%, better than gliptins monotherapy. Therefore, the aim of this project is to do the preformulation studies of linagliptin and dextromethorphan as a novel combination therapy to treat type 2 diabetes mellitus. In this work, preformulation studies were done to ascertain the particle size distribution, angle of repose, compressibility index, bulk and tapped density, dissolution profile and interaction at dissolve state. The particle size distribution were below 250μ for both linagliptin and dextromethorphan, which indicates a good dissolution pattern. Angle of repose were 22.5º and compressibility index were 18.75, while mixed linagliptin and dextromethorphan together ensures better flow ability as well as compression property. Moreover, the dissolution data suggest that, linagliptin get dissolved within 3 minutes whereas dextromethorphan takes 1.5 minutes to get dissolved in pH 6 phosphate buffer medium. On the other hand, both linagliptin and dextromethorphan did not demonstrate change in concentration in dissolve state with excipients in UV-spectrophotometer analysis, indicates no interaction among the ingredients. The methods used in the project were found to be accurate, liner and precise which put forward further work on this project for developing the novel combination therapy of linagliptin and dextromethorphan.
    Keywords
    Antidiabetic combination therapy; Diabetes; Novel antidiabetic combination
     
    Description
    This project report is submitted in partial fulfilment of the requirements for the degree of Bachelor of Pharmacy, 2018.
     
    Catalogued from PDF version of project report.
     
    Includes bibliographical references (page 72-90).
    Department
    Department of Pharmacy, BRAC University
    Collections
    • Project report (Bachelor of Pharmacy)

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