Biomedical subjects

Per Borgquist

Publications and source records attributed to Per Borgquist.

3 recordsLinked to original sources

PubMed2005

XEDS-mapping for explaining release patterns from single pellets.

A common way to formulate controlled-release (CR) pharmaceuticals is to coat pellets of active substance with a polymer film, decrease the size of the pellets and distribute them as multiple-unit dosages in capsules. To increase the understanding of the release mechanism, the pellet shape and surface structure of pellets, before and after release in microtitre plates, have been studied by scanning electron microscope and X-ray energy-dispersive spectrometry. By performing these studies we associate release profiles during the first few hours to the microscopic structure. Pellets were divided into three classes (spherical pellets, dumbbell shaped pellets and twin-pellets) according to pellet form. Cases of burst release occurred for all three shape classes due to "open-window-defects" at the surface. Areas of thinner polymer film in the neck-region of dumbbell shaped pellets broaden the range of intermediate release rates for this pellet shape. The surface of twin pellets and dumbbell shaped pellets showed more defects, which increases the release rates in comparison to spherical pellets. All pellets with high release rates revealed ruptures in the polymer film, whereas only small cracks could be traced for pellets with slow release rates. The information gained is necessary for the development of future formulations and mathematical modelling of release patterns. The pharmaceutical used as model was remoxipride coated with a polymer film of ethyl cellulose and 10 wt.% triethyl citrate.

Delayed-Action Preparations↗

PubMed2004

Simulation of the release from a multiparticulate system validated by single pellet and dose release experiments.

A previously described single-pellet release model has been simplified and modified to give predictions of the release from multiple-pellet systems, besides describing the release from single pellets. The simplified single-pellet model has been verified using single-pellet data and has been used to estimate three release-controlling parameters, namely the pellet core radius, the overall mass transfer coefficient, and the lag time. Single-pellet release experiments showed that the release from the individual film-coated drug cores resulted in a wide distribution of release profiles, a phenomenon not observed on the dose level. Therefore, the parameter estimations resulted in distributions of these parameter values. The core radius and the lag times compared well with the experimental data. The distributions were used as input data for the multiple pellet model, in order to predict the release profiles on the dose level, showing results consistent with the measured dose release. The dose-predictive ability of the model was demonstrated in simulations by studying the effect of a change in the size of the single subunits (of constant total dose), showing that smaller pellets give an increased release rate with less variation. The model for predicting dose-release profiles could be of great value in optimising the performance of an existing formulation, as well as in the development of a new controlled-release pharmaceutical.

Delayed-Action Preparations↗

PubMed2002

Simulation and parametric study of a film-coated controlled-release pharmaceutical.

Pharmaceutical formulations can be designed as Multiple Unit Systems, such as Roxiam CR, studied in this work. The dose is administrated as a capsule, which contains about 100 individual pellets, which in turn contain the active drug remoxipride. Experimental data for a large number of single pellets can be obtained by studying the release using microtitre plates. This makes it possible to study the release of the individual subunits making up the total dose. A mathematical model for simulating the release of remoxipride from single film-coated pellets is presented including internal and external mass transfer hindrance apart from the most important film resistance. The model can successfully simulate the release of remoxipride from single film-coated pellets if the lag phase of the experimental data is ignored. This was shown to have a minor influence on the release rate. The use of the present model is demonstrated by a parametric study showing that the release process is film-controlled, i.e. is limited by the mass transport through the polymer coating. The model was used to fit the film thickness and the drug loading to the experimental release data. The variation in the fitted values was similar to that obtained in the experiments.

Computer Simulation↗