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DEVELOPMENT AND EVALUATION OF EXTENDED-RELEASE BUMETANIDE TABLETS

TILLOTSON, JOHN KING
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1085067185

Abstract Details

2004, PhD, University of Cincinnati, Pharmacy : Pharmaceutical Sciences.
The focus of this dissertation was to develop and evaluate an extended-release, matrix tablet formulation of the loop diuretic bumetanide. Response surface studies including D-optimal mixture experiments and central-composite designs were used to study the effects of formulation variables on bumetanide release. Extended-release tablets of bumetanide were developed and evaluated for the impact on bumetanide release by: extended-release polymer concentration, filler excipient type and concentration, pH of dissolution media, ICH accelerated storage conditions, formula reproduction, and media pH and solubility modifiers. Also, the predictability of response surface experiments, with regard to drug release was analyzed, as was the effect of ICH accelerated storage conditions on tablet physical characteristics. It was found that both extended-release polymer and filler excipients significantly affected bumetanide release. Bumetanide release was slowed as the fraction of the extended-release polymer was increased from 20-60%. The following order of filler excipients was determined for bumetanide release (slowest to fastest): dibasic calcium phosphate, lactose, and microcrystalline cellulose. Bumetanide tablets exhibited pH-dependent drug release based upon bumetanide solubility in the study media, releasing slowest in pH 1.5 HCl buffer followed by pH 4.5 phthalate buffer, USP purified water pH 5.8, and pH 6.8 phosphate buffer. Under ICH stability conditions bumetanide extended-release tablets exhibited a significant increase in hardness after 1 month, and also, exhibited a significant decrease in release rate after 6 months. The developed formulation was found to be reproducible by f2 analysis. All pH and solubility modifiers (MgO, THAM, and SLS) were found to significantly increase the release rate of bumetanide from the developed tablets in all study media. Through careful adjustment of both the extended-release polymer and the pH modifiers a significant reduction in pH-dependent drug release was observed. The research was significant as it demonstrated that PVAP employed in amounts as low as 24% exhibits stability problems. Additionally, it was found that the addition of MgO, THAM, and SLS leads to a significant increase in the bumetanide release rater from matrix tablets in acidic pH media. Also, response surface experiments were demonstrated to be effective and predictive, with regard to formula predictions.
Dr. Adel Sakr (Advisor)
243 p.
Health Sciences, Pharmacy
Matrix; Tablet; Extended-Release; pH Modifiers; Response-surface; Bumetanide

Recommended Citations

Citations

  • TILLOTSON, J. K. (2004). DEVELOPMENT AND EVALUATION OF EXTENDED-RELEASE BUMETANIDE TABLETS [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1085067185

    APA Style (7th edition)

  • TILLOTSON, JOHN. DEVELOPMENT AND EVALUATION OF EXTENDED-RELEASE BUMETANIDE TABLETS. 2004. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1085067185.

    MLA Style (8th edition)

  • TILLOTSON, JOHN. "DEVELOPMENT AND EVALUATION OF EXTENDED-RELEASE BUMETANIDE TABLETS." Doctoral dissertation, University of Cincinnati, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1085067185

    Chicago Manual of Style (17th edition)

ucin1085067185
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© 2004, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.