Biomedical subjects

L J Leeson

Publications and source records attributed to L J Leeson.

14 recordsLinked to original sources

PubMed1991

Development of a new controlled-release formulation of chlorpheniramine maleate using in vitro/in vivo correlations.

Development of a controlled-released formulation of chlorpheniramine maleate is described, using in vitro/in vivo correlates, according to a process that has been termed "biorelevant dissolution". The process begins with simulations using several possible input rates combined with known disposition parameters of chlorpheniramine maleate. Based on desired plasma concentrations, an input rate is selected for further development which consists of a combination of clinical bioequivalence studies and further in vitro testing and simulations. The method is designed to reduce the requirements for trial and error clinical bioequivalence testing of a new controlled-release formulation.

Administration, Oral↗

PubMed1990

A better way to present posters.

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Congresses as Topic↗

PubMed1990

The development of USP dissolution and drug release standards.

Dissolution tests have been in use in the pharmaceutical industry for over 20 years, and they are official in The United States Pharmacopeia since the early 1960s. The dissolution test, reviewed primarily as a quality control tool, replaced the use of disintegration tests which had been official in The United States Pharmacopeia since 1950. Refinements in the dissolution test equipment and methodology have occurred over the years in order to enhance its relevance. The Subcommittees of the USP Committee of Revision dealing with these issues have developed and refined compendial dissolution standards and policies for conventional solid-oral dosage forms and modified-release dosage forms.

Delayed-Action Preparations↗

PubMed1989

Phenotypic differences in dextromethorphan metabolism.

Polymorphic differences in dextromethorphan metabolism were observed in three studies conducted in a total of 44 subjects (of Dutch origin) administered 60 mg dextromethorphan hydrobromide as an OROS tablet. Mean plasma dextromethorphan (DM) concentrations after a single dose and at steady state were 4-75 times higher in the poor metabolizers (PM) relative to the extensive metabolizers (EM). Following a single dose, the mean areas under the plasma concentration-time curve (AUC, 0-24 hr) of DM, total dextrorphan (DR), and total 3-hydroxymorphinan (HM) were 6.9-fold higher, 17.4-fold lower, and 11-fold lower, respectively, for the PM than for the EM. Correspondingly, steady-state AUC values were 52.8 times higher, 6.7 times lower, and 3.3 times lower for DM, total DR, and total HM, respectively, for the PM relative to the EM. Drug/metabolite ratios (DMR) for amounts excreted in the urine of DR and HM indicated polymorphism in O-demethylation of DM since DMR for PM was 352 and 338 times higher than that for EM for DR and HM, respectively. However, polymorphism in N-demethylation was not observed. Ratios of conjugated/free dextrorphan and 3-hydroxymorphinan excreted in the urine suggest also a lack of conjugative capacity in the PM, relative to the EM. The overall incidence of PM was 9.1% in this population.

Administration, Oral↗

PubMed1985

The in vitro development of extended-release solid oral dosage forms.

A system is described for developing extended-release products, based upon predicting or simulating the entire plasma level-time curve to be expected from the administration of a controlled-release oral dosage form. Termed "biorelevant dissolution," it employs the product's in vitro dissolution behavior and the drug's pharmacokinetic parameters in conjunction with a classical pharmacokinetic model. The basic system is described along with some pertinent examples.

Administration, Oral↗

PubMed1985

Oros controlled-release formulations of metoprolol: an approach to the development of a system for once daily administration.

A combined biopharmaceutical and haemodynamic approach to the development of a metoprolol Oros controlled-release delivery system for once daily administration is reported. Two studies, each involving 18 healthy volunteers, were performed in which twice daily administration of 100 mg conventional metoprolol tartrate tablets was compared with once daily administration of Oros systems containing 190 mg metoprolol fumarate but with different drug release rates. Plasma drug concentrations and beta-adrenoceptor blocking effects were measured over 24 h on days 1 and 5 of each treatment, and pre-dose in the interval between the main study days. The results of the first study with a 19 mg/h Oros system indicated that this rate was too rapid to provide the required response under steady-state dosing conditions. Theoretical calculations based on a one-compartment pharmacokinetic model and input functions for hypothetical Oros systems were then performed to define the optimal release rate for a once daily preparation. The results of the second study confirmed that a 14 mg/h system possessed the required characteristics in that it maintained more uniform beta-adrenoceptor blockade throughout 24 h, and produced pre-dosing plasma concentrations and haemodynamic effects which were identical to those for the conventional tablet twice daily regimen.

Adolescent↗

PubMed1975

The objective and timing of drug disposition studies, appendix IV. Phenylbutazone formulations: in vitro dissolution and in vivo performance.

Human plasma level studies were conducted on various phenylbutazone formulations. The resultant data indicated that the nature of the formulation had a marked influence on the rate of phenylbutazone absorption. An in vitro dissolution rate apparatus was employed in an attempt to predict potential absorption of phenylbutazone from a given formulation. Based upon the in vitro-in vivo correlation, a new phenylbutazone tablet product was developed which produced a complete and more rapid absorption of the drug.

Adult↗

PubMed1973