Controlled release from erod1ble poly(ortho ester) drug delivery systems

Sparer, Randall; Shih, Chung; Ringeisen, Cheryl D.; Himmelstein, Kenneth J.

doi:10.1016/0168-3659(84)90018-x

Cited by 51 publications

(9 citation statements)

References 6 publications

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“…Poly(ortho esters) are one class of bioerodible polymers that have been described as surface eroding systems, 3 but only circumstantial evidence to substantiate such claims has been presented. 4 These polymers are stable at alkaline pH and hydrolyze at increasingly rapid rates as the pH is lowered. Because hydrophobic poly(ortho esters) erode at very slow rates at body pH, many applications require an increased hydrolysis rate, which can be achieved by providing an acidic environment within the polymer matrix.…”

Section: Introductionmentioning

confidence: 99%

Hydrolysis and Erosion Studies of Autocatalyzed Poly(ortho esters) Containing Lactoyl−Lactyl Acid Dimers

1999

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Poly(ortho esters) based on 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5.5]undecane, 1,10-decanediol, and 1,10-decanediol dilactate were prepared and their hydrolysis in phosphate buffer at 37 °C and pH 7.4 was determined as a function of time. Specifically, kinetics of polymer weight loss, polymer molecular weight changes, release of lactic acid and release of propionic acid were determined. A significant decrease in molecular weight occurred within about 20 days. Weight loss and evolution of hydrolysis product occurred after an induction period that decreased with increasing content of the lactoyl−lactyl segment in the polymer. After the induction period, a concomitant rate of weight loss and release of hydrolysis products was noted. The rate increased with increasing content of the lactoyl−lactide segment. After a certain time period, size-exclusion chromatography revealed the formation of a peak at an apparent molecular mass of about 550 Da. The compounds under the peak were analyzed by electrospray ionization/mass spectrometry (ESI/MS) and found to consist of a multiplicity of lower molecular weight polymer hydrolysis fragments. On the basis of expected hydrolysis products, it was possible to assign a structure to most molecular weight peaks in the ESI/MS spectrum. The data were found to be consistent with a hydrolysis that takes place predominantly in the surface layers of the solid polymer.

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Section: Introductionmentioning

confidence: 99%

Hydrolysis and Erosion Studies of Autocatalyzed Poly(ortho esters) Containing Lactoyl−Lactyl Acid Dimers

1999

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“…Because poly (ortho esters) are stable in base, incorporation of a basic excipient such as Mg(OH)2 into the matrix prevents bulk erosion even though a small amount of water permeates the hydrophobic matrix [7]. Using this methodology, long-term surface-erosion can be achieved by relying on polymer erosion that takes place in the surface layers where the basic excipient has been neutralized by the external environment.…”

Section: Use Of Acid Anhydridesmentioning

confidence: 98%

“…Thus, useful devices having lifetimes from hours to about one month can be prepared by using potential acids such as phthalic anhydride or 2,3-pyridene dicarboxylic anhydride [7]. As expected, rate of polymer erosion and concomitant drug release depends on the pKa of the diacid and its concentration in the matrix.…”

Section: Use Of Acid Anhydridesmentioning

confidence: 99%

Synthesis and Use of Poly (Ortho Esters) for the Controlled Delivery of Therapeutic Agents

Heller

1988

Journal of Bioactive and Compatible Polymers

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“…The catalytic action of acid anhydrides depends on reaction with water to yield a diacid, which then catalyzes hydrolysis of the matrix (Shih et al, 1984;Sparer et al 1984). Polymer erosion, and hence rate of drug release, can be controlled by the amount of incorporated anhydride.…”

Section: Acid Anhydride Excipientsmentioning

confidence: 99%

Directed Drug Delivery

Borchardt¹,

Repta²,

Stella³

1985

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All rights reservedNo part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. PREFACEThis book is based on the proceedings of the symposium entitled "Directed Drug Delivery: A Multidisciplinary Problem," which was held in Lawrence, Kansas on October 17-19, 1984. The purpose of the symposium and this book is to focus on the multidisciplinary nature of drug delivery. Development of a successful drug delivery system requires contributions from various scientific disciplines, including pharmaceutical chemistry, analytical chemistry, medicinal chemistry, biochemistry, pharmacology, toxicology, and clinical medicine. The contents of this volume illustrate the importance of the various disciplines in identifying the problems and approaches for the development of a rational and effective drug delivery system. Thus the information provided herein will be of value not only to the pharmaceutical chemists who are responsible for dosage form design, but also to the pharmacokineticists, pharmacologists, and clinicians involved in biological evaluation of drug delivery systems. The volume should also be of interest to the analytical chemists who must provide technology to quantitcltively evaluate drug delivery. Additionally, this work will also interest the biochemists and medicinal chemists involved in drug discovery, since the drug delivery system often plays a major role in determining the success or failure of a new drug entity.Each speaker at the symposium was requested to contribute a chapter reviewing the contribution of their major discipline to the development of a successful drug delivery system. Topics covered in this volume include pharmacokinetics and pharmacodynamic factors (Section A) and physiological and biochemical factors (Section B) that influence directed drug delivery, various approaches to controlled and targeted drug delivery, including physical (SectionC) and biological (Section D) systems, as well as appropriate and important analytical chemistry topics (Section E).The individual chapters in this volume represent comprehensive, up-to-date reviews of the subject material. However, to gain maximum appreciation for the multidisciplinary nature of drug delivery, the editors suggest a thorough reading of the entire volume.

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Controlled release from erod1ble poly(ortho ester) drug delivery systems

Cited by 51 publications

References 6 publications

Hydrolysis and Erosion Studies of Autocatalyzed Poly(ortho esters) Containing Lactoyl−Lactyl Acid Dimers

Hydrolysis and Erosion Studies of Autocatalyzed Poly(ortho esters) Containing Lactoyl−Lactyl Acid Dimers

Synthesis and Use of Poly (Ortho Esters) for the Controlled Delivery of Therapeutic Agents

Directed Drug Delivery

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