Effects of gastrointestinal transit on plasma concentrations of drugs from enteric-coated
pellet formulations were demonstrated using pharmacokinetic models
describing plasma concentrations of drugs from various enteric-coated pellet
formulations. Gastric emptying time, lag time of emptying, and drug release rate
from pellets in the small intestine, along with other pharmacokinetic parameters of
drugs, were used to construct pharmacokinetic models. The models were then
evaluated by comparing simulated plasma concentrations of model drugs from
Monte Carlo simulations to observed plasma concentrations of these drugs from the
literature. Results showed that the models described plasma concentrations of drugs
from enteric-coated pellet formulations very well. Pharmacokinetic models
describing plasma concentrations of drug from mixed immediate-release and
enteric-coated pellet formulations were also used in simulations of bioequivalence
studies. Results from the research are very useful in designing generic products of
mixed pellet formulation and in refining or selecting the final product for actual
bioequivalence study.
Development of crushable enteric-coated formulations was presented. Nonpareil
sugar pellets were spray-loaded with mixed amphetamine salts. Drug-loaded pellets
were subsequently spray-coated with enteric polymer, hydrophilic gel-forming
polymer, enteric polymer and/or mixture of insoluble polymer and hydrophilic
polymer. The resulting pellets were then spray-coated with disintegrant and
compressed to form crushable tablets. Dissolution testing of both non-compacted
crushable enteric-coated tablets and crushed tablets showed that the intact crushable
tablet formulations and the crushed tablet formulations were able to prevent the
majority of the drug from being released in a simulated gastric dissolution medium
within first 2 hours.
Concept and formulations of "leaky" enteric-coated pellets were presented. "Leaky
enteric-coated pellets" formulation is defined as enteric-coated pellets that allow
some of the drug to be released from the formulation in acidic dissolution medium.
Different approaches of making leaky enteric-coated pellets using spray-coating
techniques were presented. Plasma concentrations of drug from leaky enteric-coated
pellet formulations were simulated using computer simulations. The present
research was based on the hypothesis that leaky enteric-coated pellets formulations
were able to provide sustained-release effect on plasma concentration profiles of
drugs that have the absorption window without jeopardizing their bioavailability or
with improved bioavailability. / Graduation date: 2005
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/28850 |
| Date | 16 November 2004 |
| Creators | Watanalumlerd, Prapoch |
| Contributors | Ayres, James W. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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