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Biomedical subjects

P V Pedersen

Publications and source records attributed to P V Pedersen.

29 records · Page 2Linked to original sources
PubMed1977

New method for characterizing dissolution properties of drug powders.

Various multiparticulate dissolution models that assume a log-normal particle-size distribution are fitted by nonlinear least-squares regression to data from the dissolution of micronized glyburide. Estimates of parameters describing the effective initial particle-size distribution are obtained, together with estimates of the specific dissolution rate parameter. A dissolution equation based on an ideal, untruncated, log-normal distribution, with the single particles dissolving according to the Hixson-Crowell cube root law, is the best model. The dissolution behavior of glyburide can be well described by this model in terms of the specific dissolution rate parameter and one other parameter accounting for the distribution effect. The estimation of these two parameters represents a more exact way of describing the dissolution characteristics of drug powders than previous approaches. The method should be of interest in the quality control of drugs that may cause bioavailability problems because of dissolution rate-limited absorption.

Chemistry, Pharmaceutical↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1976

Necrotising enterocolitis of the newborn--is it gas-gangrene of the bowel?

Necrotising enterocolitis (N.E.C.) of the newborn is thought to be caused by ischaemia of the bowel. This would favour the conversion of clostridial spores, which can occur very early in the intestinal tract of newborns, to toxin-producing, invading bacilli. The histology of resected gut specimens from 6 of 7 N.E.C. patients who had undergone operation was similar to that in cases of gas-gangrene of the bowel and that in experimentally provoked pneumatosis cystoides intestinalis. In one case Clostridium perfringens type A was cultured in great number by anaerobic technique. The clostridia in these cases may have played an important role in the development of N.E.C.

Clostridium perfringens↗
PubMed1976

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↗
PubMed1976

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↗
PubMed1975

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↗
PubMed1975

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↗