Biomedical subjects

P J Missel

Publications and source records attributed to P J Missel.

5 recordsLinked to original sources

PubMed2006

Adaptation of USP types II and IV controlled release assays for sparingly soluble compounds by direct eluent HPLC analysis.

Measurement of drug release of a sparingly soluble drug by conventional methods proceeds very slowly without the aid of surfactants. Two preliminary automated methods were developed that increase sensitivity and accelerate such studies by working at very small reservoir volumes. All high pressure liquid chromatography (HPLC) equipment components were commercially available. Results are presented for the drug release of a single pellet of the sparingly soluble drug Eliprodil in two types of drug release experiments using (1) a stirred cell and (2) a flow-through method. Release rates measured from each method were comparable.

Algorithms↗

PubMed1997

Transient analysis of ocular drug delivery: zero-volume effect.

Dose volume reduction is one method for reducing the nonproductive loss of ophthalmic drugs caused by premature drainage from the precorneal area. A new mathematical method is presented for calculating the bioavailability enhancement achieved by the dose volume reduction method. This new model suggests that the steady-state assumption used in a previous paper overestimated the bioavailability enhancement, depending upon physical factors such as distribution and diffusion coefficients of the drug in tissue and solution. The analysis shows that transient effects can make a difference up to a complete elimination of the zero-volume effect in those cases where the distribution coefficient is large and the permeability coefficient is small (i.e., for large, lipophilic molecules).

Absorption↗

PubMed1992

Drug release profiles of ophthalmic formulations. 1. Instrumentation.

An experimental method is described for measuring time-release profiles of drugs from various ophthalmic dosage forms. This in vitro method is carried out under conditions nearly representative of those observed in vivo. Specifically, we have reproduced in vitro the small volume and the slow exchange rate of the human precorneal tear reservoir. Volumes on the order of 8-30 microL are achievable. The concentration of drug downstream from the sample reservoir is analyzed nearly continuously and the entire release profiles are appropriate for modeling. This analytical system has been used to study drug release kinetics from controlled release formulations such as gels and suspensions. The method is compared with alternative techniques.

Calibration↗

PubMed1991

Limits on optimizing ocular drug delivery.

The problem of optimizing ocular bioavailability of topically applied ophthalmic drugs is discussed. A formula for drug concentration in the tear film is derived using well-known pharmacokinetic relationships and a first-order drug decay model for the tear film. The time integral of the tear film concentration is then related to ocular bioavailability. The results of this analysis show that: (1) high corneal permeability (corresponding to lipophilic compounds) produces the highest bioavailability; (2) the bioavailability of drugs with high corneal permeability is relatively unaffected by drug volume; and (3) by making the dosage volume sufficiently small, a bioavailability improvement factor of approximately 4 can be obtained for drugs with low corneal permeability.

Administration, Topical↗

PubMedDate not supplied

Finite element modeling of diffusion and partitioning in biological systems: the infinite composite medium problem.

Four methods are proposed for modeling diffusion in heterogeneous media where diffusion and partition coefficients take on differing values in each subregion. The exercise was conducted to validate finite element modeling (FEM) procedures in anticipation of modeling drug diffusion with regional partitioning into ocular tissue, though the approach can be useful for other organs, or for modeling diffusion in laminate devices. Partitioning creates a discontinuous value in the dependent variable (concentration) at an intertissue boundary that is not easily handled by available general-purpose FEM codes, which allow for only one value at each node. The discontinuity is handled using a transformation on the dependent variable based upon the region-specific partition coefficient. Methods were evaluated by their ability to reproduce a known exact result, for the problem of the infinite composite medium (Crank, J. The Mathematics of Diffusion, 2nd ed. New York: Oxford University Press, 1975, pp. 38-39.). The most physically intuitive method is based upon the concept of chemical potential, which is continuous across an interphase boundary (method III). This method makes the equation of the dependent variable highly nonlinear. This can be linearized easily by a change of variables (method IV). Results are also given for a one-dimensional problem simulating bolus injection into the vitreous, predicting time disposition of drug in vitreous and retina.

Biological Transport, Active↗