Gastrointestinal (GI) transit data were collected using pigs
as animal models. Density and size effects of non-disintegrating
dosage forms on GI transit were investigated. Total GI transit
times range from 2 to 33 days for 22 administrations of these nondisintegrating
dosage forms. Pigs are found to not be an
appropriate animal model for studying bioavailability or GI transit
of non-disintegrating, non-erodible oral release dosage forms.
Development of controlled release dosage forms where the
mechanism of drug release is diffusion through polymeric membrane
formed via film coating utilizing fluid-bed technology requires
optimization of several processing and formulation variables. The
influence of a processing variable (nozzle orifice opening) and a
few formulation variables (individual vs. combination plasticizer,
or a water-insoluble additive) on dissolution of a model drug
(acetaminophen) spray coated with Aquacoat® were studied.
Pharmacodynamic and pharmacokinetic information for a model
drug (acetaminophen) and computer simulation were used to develop a
dosage form with a 12 hour sustained release for oral administration
to children and adults for maximum analgesic and
antipyretic effect. Simulated plasma acetaminophen concentration-time
curves were similar to observed bioavailability study
profiles. In vitro and preliminary in vivo results from an adult
human volunteer indicate that sustained therapeutic saliva
acetaminophen concentration is possible using the newly developed
acetaminophen molded tablet dosage form.
The bioavailability of the new, oral controlled release
acetaminophen molded tablet relative to a commercially available
product (Extra-Strength Tylenol® caplet) was evaluated in 8
healthy, adult volunteers. Multiple doses of these two products
were administered in a two-way cross-over design. Bioavailability
of the new sustained release molded tablet is comparable to that of
the immediate release product. Polymer coated acetaminophen beads
were effective in maintaining saliva acetaminophen concentrations
of 5 μ/ml over a 12 hour dosing interval. / Graduation date: 1991
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/37368 |
| Date | 10 April 1991 |
| Creators | Hossain, Mohammad |
| Contributors | Ayres, James W. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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