Application and evaluation of extended release technology to loop diuretics / Ehab Ahmed Mamdouh Hamed .

By:

Hamed, ehab ahmed mamdouh [author]

Contributor(s):

Material type: Text

TextCincinnati, Ohio : University of Cincinnati, 2002Description: 208 pages : illustrations ; 23 cmContent type:

text

Media type:

unmediated

Carrier type:

volume

Subject(s):

Pharmaceutical Sciences

DDC classification:

21 615.1 H.E.A

Dissertation note: Thesis (Ph.D.)--University of Cincinnati, 2002 Summary: Loop diuretics offer great advantages in treating edematous states associated with congestive heart failure, liver cirrhosis and kidney failure owing to their intense diuretic effect. Evidences suggested the diuretic effect can be exaggerated by careful control of the rate at which loop diuretics are made available to the urinary tubules. If optimally designed, peroral extended release formulation can provide better utilization of the same total dose of loop diuretic, an effect of utmost importance in edematous patients with high resistance to loop diuretics. Bumetanide multiparticulate immediate and extended release formulations were developed and tested in rabbits. A novel multiple response optimization technique based on superimposing contour diagrams was developed and successfully used to optimize bumetanide release. Instability in drug release from multiparticulate formulations after storage warrants in depth investigation of different formulation and processing factors controlling drug release. Curing time, temperature, plasticizer level, coating polymer lipophilicity, and the use of hydrophilic seal coat were explored in this study. The findings proved instability in bumetanide release is attributed to drug migration into the film coat during storage. Careful selection of plasticizer level and curing conditions together with the use of hydrophilic seal coat prevented drug migration and stabilized drug release after storage. When compared to immediate release formulation in rabbits, equivalent amounts of bumetanide were excreted from both formulations yet at different rates. The slow delivery of bumetanide from the extended release formulation improved its diuretic and natriuretic efficiencies within the first day after dosing. The activation of compensatory mechanisms is thought to diminish the response to extended release bumetanide formulation within the second day. While providing comparable diuretic and saliuretic effects to that of immediate release formulation, extended release bumetanide formulation can offer the advantage of avoiding the initial, unpleasant and intense diuretic effect experienced with immediate release formulations

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Holdings
Item type	Current library	Collection	Call number	Status	Date due	Barcode
Thesis	Main library C5 PHD	Pharmacy ( Pharmaceutical chemistry )	615.1 H.E.A (Browse shelf(Opens below))	Not for loan		00016452

Includes abstract

Thesis (Ph.D.)--University of Cincinnati, 2002

Includes bibliographical references

Loop diuretics offer great advantages in treating
edematous states associated with congestive heart failure,
liver cirrhosis and kidney failure owing to their intense
diuretic effect. Evidences suggested the diuretic effect
can be exaggerated by careful control of the rate at which
loop diuretics are made available to the urinary tubules.
If optimally designed, peroral extended release
formulation can provide better utilization of the same
total dose of loop diuretic, an effect of utmost
importance in edematous patients with high resistance to
loop diuretics. Bumetanide multiparticulate immediate and
extended release formulations were developed and tested in
rabbits. A novel multiple response optimization technique
based on superimposing contour diagrams was developed and
successfully used to optimize bumetanide release.
Instability in drug release from multiparticulate
formulations after storage warrants in depth investigation
of different formulation and processing factors
controlling drug release. Curing time, temperature,
plasticizer level, coating polymer lipophilicity, and the
use of hydrophilic seal coat were explored in this study.
The findings proved instability in bumetanide release is
attributed to drug migration into the film coat during
storage. Careful selection of plasticizer level and curing
conditions together with the use of hydrophilic seal coat
prevented drug migration and stabilized drug release after
storage. When compared to immediate release formulation in
rabbits, equivalent amounts of bumetanide were excreted
from both formulations yet at different rates. The slow
delivery of bumetanide from the extended release
formulation improved its diuretic and natriuretic
efficiencies within the first day after dosing. The
activation of compensatory mechanisms is thought to
diminish the response to extended release bumetanide
formulation within the second day. While providing
comparable diuretic and saliuretic effects to that of
immediate release formulation, extended release bumetanide
formulation can offer the advantage of avoiding the
initial, unpleasant and intense diuretic effect
experienced with immediate release formulations

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