N-isopropylacrylamide copolymers for modulated gastrointestinal drug delivery

Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Ramkissoon-Ganorkar, Loksidh Devi
Title N-isopropylacrylamide copolymers for modulated gastrointestinal drug delivery
Date 1999-05
Description Random pH-/temperature-sensitive terpolymers of N-isopropylacrylamide (NIPAAm), butylmethacrylate (BMA) and acrylic acid (AA) of varying molecular weight (MW) were synthesized with NIPAAm/BMA/AA feed mol ratio of 85/5/10. These terpolymers were designed for specific lower critical solution temperature (LCST) behavior with pH. The polymers allow aqueous drug loading under mild temperature and pH conditions, thereby avoiding the use of organic solvents. The terpolymers were used to prepare polypeptide-releasing beads. An aqueous polymer/drug solution was dropped into an oil phase at a temperature above the LCST of the polymer solution. This led to polymer precipitation and drug entrapment. The advantage of this system is that the drug is physically entrapped in the polymeric bead; no chemical modification of the drug is involved. The loading efficiency of the polymeric beads for any drug can be optimized by controlling the ionic strength, temperature, polymer MW, polymer composition and polymer concentration. The bead release profile was a function of the MW of polymers and pH of the release medium. An increase in polydispersity improved the stability of the polymeric system and in consequence decreased polymer dissolution kinetics and drug release rate. A linear uncrosslinked system was used to modulate drug release rate simply by modifying polymer MW and polydispersity. The results of the present study have direct implications in the design of controlled release formulations. At pH 2.0 and 37°C (above LCST), the polymeric system is insoluble and does not release drug. At pH 7.4 and 37°C (below LCST), the polymeric beads dissolve or swell and release drug at a rate dependent on the polymer MW and polydispersity. Low MW and narrow polydisperse polymeric beads displayed a dump-like release profile and dissolved within 2 hours (bead dissolution-controlled release mechanism), while the high MW and broad polydisperse polymeric beads swelled only and released drug slowly over a period of 8 hours (drug diffusion- and swelling-controlled release mechanism) and the intermediate MW beads released drug over a period of 4 hours (swelling- and dissolution-controlled mechanism). The unique properties of the pH/temperature-sensitive polymeric bead make it a potential system for oral peptide/protein delivery to different regions of the intestinal tract.
Type Text
Publisher University of Utah
Subject MESH Drug Delivery Systems; Gastrectomy
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of “N-isopropylacrylamide copolymers for modulated gastrointestinal drug delivery” Spencer S. Eccles Health Sciences Library.
Rights Management © Loksidh (Chaaya) Devi Ramkissoon-Ganorkar, To comply with copyright, the file for this work may be restricted to The University of Utah campus libraries pending author permission.
Format Medium application/pdf
Format Extent 4,302,792 bytes
Identifier undthes,4084
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Master File Extent 4,302,827 bytes
ARK ark:/87278/s6cc12j3
Setname ir_etd
Date Created 2012-04-24
Date Modified 2012-04-24
ID 191796
Reference URL https://collections.lib.utah.edu/details?id=191796
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