Ann R. Comfort

Novartis (Switzerland)

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Steven M. Dinh

Florida International University

Róbert Langer

Massachusetts Institute of Technology

Elizabeth C. Albert

Massachusetts Institute of Technology

Ihor Shevchuk

Lviv Polytechnic National University

Bret Berner

Seattle University

John D. DeNuzzio

Becton Dickinson (United States)

Elizabeth Quadros

Ligand Pharmaceuticals (United States)

Yanfeng Wang

Wuhan University

Tycho Heimbach

Merck & Co., Inc., Rahway, NJ, USA (United States)

Jin‐Young Koh

University of Iowa

Cooperative Institutions

Novartis (Switzerland)

Novartis (United States)

Massachusetts Institute of Technology

University of Florida

Columbus Oncology and Hematology Associates

Merck & Co., Inc., Rahway, NJ, USA (United States)

Foundation for Biomedical Research

National Cancer Centre Singapore

The University of Tokyo

United States Military Academy

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Drug Delivery Systems

Kirk-Othmer Encyclopedia of Chemical Technology (2000)

Elizabeth Quadros Ann R. Comfort Steven M. Dinh Bret Berner

Abstract The concepts of drug delivery are described, focusing on the application of polymer chemistry to design a well‐characterized controlled dosage form that produces the desired drug delivery profile. In order to design a system, both drug release from the system, ie, desorption or dissolution, and absorption across the relevant biological membrane are measured. The physiology and barrier properties of different routes of drug delivery, which include oral, rectal, transdermal, buccal, nasal, pulmonary, ocular, and vaginal, are described. The mechanisms that govern drug release from systems include diffusion (including osmotic), chemical, swelling, and external control, such as iontophoresis or electromechanical devices. Examples are given of commercially available systems from each class, including implants, oral osmotic devices, transdermal and ocular systems, and infusion pumps. Characterization of the physical and chemical properties of the system components is described, as well as the different types of manufacturing processes and characterization of the final system, including drug release and adhesion, if relevant.

Iontophoresis

10.1002/0471238961.0418210717210104.a01

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Citations (0)

Intelligent Materials for Controlled Release

ACS symposium series (1999)

Steven M. Dinh John D. DeNuzzio Ann R. Comfort

Small molecular weight crosslinking agents containing hydrolyzable bonds were photopolymerized with poly(ethylene oxide) in order to decrease the pore size of the gels. The resulting cogels decreased in equilibrium swelling volume (pore size) as the concentration of crosslinker increased. The initial release profile of the model protein albumin showed a decreased burst in the presence of small molecular weight crosslinkers in the photopolymerized hydrogels.

Poly ethylene

10.1021/bk-1999-0728

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Citations (25)

In vitro characterization of a solvent-controlled nitroglycerin transdermal system

Journal of Controlled Release (1995)

Ann R. Comfort Ihor Shevchuk John H. Otte Steven M. Dinh

Nitroglycerin (drug)

10.1016/0168-3659(94)00095-c

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Citations (4)

Estimation of plasma cholesterol fractions by elution from paper.

PubMed (1954)

Ann R. Comfort

Source

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Correlation and Prediction of Moisture-Mediated Dissolution Stability for Benazepril Hydrochloride Tablets

Pharmaceutical Research (2004)

Shoufeng Li Bill Wei Santo Fleres Ann R. Comfort Alan E. Royce

10.1023/b:pham.0000022408.91151.64

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Citations (22)

Effects of psychoactive drugs on ejaculation

American Journal of Psychiatry (1979)

Ann R. Comfort

Ejaculation

Psychoactive drug

10.1176/ajp.136.1.124b

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Citations (5)

Immobilized enzyme cellulose hollow fibers: I. Immobilization of heparinase

Biotechnology and Bioengineering (1989)

Ann R. Comfort Elizabeth C. Albert Róbert Langer

The immobilization of heparinase to tresyl-chloride-activated cellulose hollow fibers for the removal of heparin from the bloodstream was examined. Whole blood can be circulated through cellulose hollow fibers without hemolysis and the tresyl chloride chemistry provides a strong linkage which limits the release of the enzyme from the support. The tresylation and immobilization methods were modified and optimized to improve the heparinase activity retained by cellulose. Pretreatment of the hollow fibers with 0.05/V sodium hydroxide increased the degree of tresylation and the immobilization yield by a factor of five. The use of triethylamine as the organic base in the tresyl chloride activation resulted in threefold greater activity retention by the support than when pyridine was used. Together, sodium hydroxide pretreatment and triethylamine enhanced the activity retained by cellulose to 26.2 +/- 7.0% of that bound to the support. The activity retention was also a function of the technique used for immobilization. The best results were achieved when the enzyme was applied to the activated fibers once every 12 to 24 h for a total of four times. The active enzyme loading on the fibers was 0.3 mg heparin degraded/h cm(2) when 4.5 microg protein/cm(2) was bound to the fibers.

10.1002/bit.260341104

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Citations (23)

Temporally controlled transdermal system: biphasic transdermal delivery of nitroglycerin

Journal of Membrane Science (1994)

Steven M. Dinh Ann R. Comfort Ihor Shevchuk Bret Berner

Nitroglycerin (drug)

Delivery system

10.1016/0376-7388(94)80106-1

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Citations (4)

Stability and immunologic activity of immobilized heparinase and bilirubin oxidase.

PubMed (1988)

Ann R. Comfort C J Mullon Jin‐Young Koh Elizabeth C. Albert C P Tosone

Two model enzymes, heparinase and bilirubin oxidase, were immobilized via cyanogen bromide, tresyl chloride, epoxide, or carbodiimidazole activated natural and synthetic matrices. The supports released enzymes for 4-20 hr in vitro at 37 degrees C. The most stable linkage was formed by tresyl chloride and oxirane activated supports. No immune response was detected 11 or 21 days after single i.v. injection to New Zealand white rabbits. Acute exposure to the enzyme produced a weak positive response.

Cyanogen bromide

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Citations (1)

Immobilized enzyme cellulose hollow fibers: II. Kinetic analysis

Biotechnology and Bioengineering (1989)

Ann R. Comfort Elizabeth C. Albert Róbert Langer

Immobilized enzyme hollow fibers may be useful in the purification or treatment of whole blood under clinical conditions. In this study, catalytically pure heparinase was immobilized to cellulose to analyze the feasibility for the removal of heparin's anticoagulant activity from whole blood. The kinetics of catalytically pure heparinase immobilized to regenerated cellulose hollow fibers were quantified with respect to mass transfer coefficient and enzyme loading. The kinetic analysis showed that increases in the mass transfer coefficient of heparin in the fiber lumen decreased the apparent Michaelis constant while increases in enzyme activity immobilized to the fiber lumen increased the apparent Michaelis constant. The apparent Michaelis constant was an order of magnitude greater than the intrinsic K(m) value for the system. The intrinsic K(m) value for heparinase-cellulose is 0.4 +/- 0.3 mg/mL (N = 6) and it is the same order of magnitude as the K(m) value for soluble heparinase.

10.1002/bit.260341105

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Citations (9)