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Biomedical subjects

K F Brown

Publications and source records attributed to K F Brown.

9 recordsLinked to original sources

General class of multiparticulate dissolution models.

The dissolution of multiparticulate systems under sink and nonsink conditions can be described rigorously according to a generally applicable formula on the basis of the single-particle dissolution model and the initial particle distribution. The kinetic model for log-normal systems dissolving under sink conditions is extended to nonsink conditions as a specific example. The equation presented describes a general class of multiparticulate models for various values of the dispersion parameter and the dissolution capacity coefficient.

Kinetics

Method of obtaining drug-macromolecule binding parameters directly from dynamic dialysis data.

A new method of treating dynamic dialysis data to obtain binding parameters for drug-macromolecule interactions is presented. This method allows the determination of binding parameters directly from dialysis data according to a theoretical model. It is not necessary to determine the dialysis rate constant accurately in a separate experiment, and bias is not introduced due to differentiation. The proposed method should be applicable where the drug is substantially bound to the dialysis membrane.

Albumins

Theoretical isotropic dissolution of nonspherical particles.

Equations are derived for the isotropic dissolution of single particles, considering simple forms of the six crystal systems. These can be summarized by three basic equations which are approximated well, and in some cases exactly, by the dissolution equation for a hypothetical spherical particle of specified diameter. Formulas are given to enable calculation of this diameter and to minimize the weighted errors in the approximations. Spherical approximations provide a simple basis for calculating the dissolution profile of real multiparticulate systems which are difficult to describe otherwise. Spherical approximations based on equal surface area or volume result in large errors.

Crystallization

Experimental evaluation of three single-particle dissolution models.

The dissolution of the 60-85-mesh fraction os recording, flow-through dissolution apparatus equipped with a dissolution cell; it was particularly suitable for kinetic analysis of multiparticulate systems. By using a time-scaling approach, experimental data are compared with theoretical calculations to evaluate, quantitatively, which of three single-particle dissolution models best describes the data and how well the multiparticulate kinetics can be explained mathematically. The nonspherical tolbutamide particles are replaced in the calculations by a hypothetical system of spherical particles that appears to be log-normally distributed. This procedure permits the calculation of the intrinsic dissolution profile, considering both size distribution and particle shape effects.

Kinetics

Dissolution profile in relation to initial particle distribution.

A general equation was derived describing the complete and exact dissolution profile of powders under sink conditions. It is applicable to powders having any initial particle-size distribution, with particles dissolving according to any explicit equation. It was applied to develop an equation for the dissolution of log-normal powders that is more generally applicable than previous approaches. The effect of change in initial particle-size distribution parameters on the dissolution profile is illustrated.

Computers

Size distribution effects in multiparticulate dissolution.

The evaluation of models for single-particle dissolution, based on multiparticulate dissolution data, is complicated by the distribution effect present when the particles are not truly monodispersed. By using simulated data, it is shown that remarkably good linearity can be obtained with log-normal powders using an incorrect model. It is suggested that particle-size analysis is necessary to enable calculation of the distribution effect and to prevent this type of misinterpretation. The change in particle-size distribution during dissolution is calculated and shows potential for distinguishing between two, but not all three, of the models investigated. Four theoretical rules for multiparticulate dissolution are stated and discussed. The concept of "time scaling" is presented. By using this procedure, it should be possible to reduce considerably computational errors arising from nonlinear dissolution data. It is demonstrated that dissolution profiles can be transformed to a standard form, enabling the distribution effect to be evaluated without interference from rate or particle-size parameters.

Kinetics