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29150.pdf (5.27 MB)
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Use of Silicone Adhesive for Improving Oral Controlled Delivery
Author Info
Tolia, Gaurav
ORCID® Identifier
http://orcid.org/0000-0002-4130-5578
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1521190743860228
Abstract Details
Year and Degree
2018, PhD, University of Cincinnati, Pharmacy: Pharmaceutical Sciences/Biopharmaceutics.
Abstract
Controlled release oral dosage form offers great advantages over conventional dosage form by providing steady drug plasma concentration, decreasing the frequency of administration, and providing enhanced patient compliance. However, orally ingested tablet is exposed to varying pH conditions and fluctuating mechanical agitations during its travel through the gastrointestinal tract (GIT). Selection of materials that provide controlled release mechanism to the oral dosage form is important as they can a) minimize drug release rate fluctuations for ionizable drugs during its travel along the changing pH environment of the GIT and b) maintain the release rate mechanism even when subjected to the physiological mechanical agitation forces. To examine these two important requirements, matrix tablets prepared using low glass transition temperature (Tg) silicone pressure sensitive adhesive (PSA) were evaluated and compared with matrix tablets prepared using high Tg ethyl cellulose (EC). Specifically, the effect of dissolution medium pH on drug release from binary tablets consisting of the polymer and ionizable model drugs verapamil hydrochloride and diclofenac sodium was studied using USP dissolution apparatus (without mechanical stress). The effect of simulated physiological mechanical stress agitation on drug release was studied using dissolution stress test apparatus for non-ionizable model drug acetaminophen. Mechanical properties, physical structures, electrical resistance, water uptake, and contact angle of pure polymer films and of matrix tablets were studied to understand the relationships of these factors to drug release. Our study indicated that increasing polymer amount decreased drug release rate from both silicone PSA and EC tablets using USP dissolution apparatus. However, silicone PSA tablets showed lower friability compared to EC tablets. The application of physiological simulated mechanical stress affected drug release from high Tg EC tablets that resulted in burst release of acetaminophen whereas silicone PSA tablets were resistant to the mechanical effect. Rate and extent of water uptake into matrix tablets during drug release experiments were related to polymer compressibility properties. In addition, tablet water uptake on exposure to dissolution medium correlated to the mechanical properties of the polymer. Highly compressible silicone PSA showed lower water uptake and higher electrical resistance compared to EC tablets. Silicone PSA matrix tablets showed pH-independent release of verapamil HCl. However, EC matrix tablet of verapamil HCl did not show pH-independent release. EC matrix tablets also showed larger difference in drug release compared to silicone PSA matrix for weakly acidic model drug diclofenac sodium when exposed to acid dissolution medium. Silicone PSA provides both mechanical and electrical resistance properties which may be important in choosing a polymer for oral matrix tablets. The results suggest that silicone PSA is a promising excipient for oral controlled release to minimize the effect of mechanical agitation and dissolution medium pH on drug release.
Committee
Kevin Li, Ph.D. (Committee Chair)
Pankaj Desai, Ph.D. (Committee Member)
Sergey Grinshpun, Ph.D. (Committee Member)
Gerald Kasting, Ph.D. (Committee Member)
Gary Kelm, Ph.D. (Committee Member)
R. Randall Wickett, Ph.D. (Committee Member)
Pages
202 p.
Subject Headings
Pharmaceuticals
Keywords
Controlled release
;
Drug delivery
;
Silicone polymer
;
Drug release
;
Matrix tablet
;
Polymer properties
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Refworks
EndNote
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Citations
Tolia, G. (2018).
Use of Silicone Adhesive for Improving Oral Controlled Delivery
[Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1521190743860228
APA Style (7th edition)
Tolia, Gaurav.
Use of Silicone Adhesive for Improving Oral Controlled Delivery.
2018. University of Cincinnati, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1521190743860228.
MLA Style (8th edition)
Tolia, Gaurav. "Use of Silicone Adhesive for Improving Oral Controlled Delivery." Doctoral dissertation, University of Cincinnati, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1521190743860228
Chicago Manual of Style (17th edition)
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Document number:
ucin1521190743860228
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306
Copyright Info
© 2018, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.