Search

Biorelevant dissolution instruments represent an important tool for pharmaceutical research and development. These instruments are designed to simulate the dissolution of drug formulations in conditions most closely mimicking the gastrointestinal tract. In this work, we focused on the optimization of dissolution compartments/vessels for an updated version of the biorelevant dissolution apparatus-Golem v2. We designed eight compartments of uniform size but different inner geometry. The dissolution performance of the compartments was tested using immediate release caffeine tablets and evaluated by standard statistical methods and principal component analysis. Based on two phases of dissolution testing (using 250 and 100 mL of dissolution medium), we selected two compartment types yielding the highest measurement reproducibility. We also confirmed a statistically ssignificant effect of agitation rate and dissolution volume on the extent of drug dissolved and measurement reproducibility., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

The effect of process scale-up from 4 to 400-L high-shear granulator on the release kinetics of the active ingredient from pharmaceutical granules has been investigated. The dissolution and disintegration rates of the granules were measured simultaneously by the combination of UV/vis spectroscopy and static light scattering. The granule batches were found to consist of sub-populations with qualitatively different dissolution behavior: "weaker" granules that disintegrated during dissolution, and "stronger" granules that retained their size and from which the active ingredient was gradually leached. The existence of these sub-populations was attributed to non-uniform distribution of normal and shear forces that prevail in granulators of different size. This hypothesis was confirmed by preparing granules at increasing values of the Froude number at the 4-L scale, and observing a transition from the break-up dissolution mode to the leaching dissolution mode with increasing granule densification. The simultaneous observation of solute concentration and particle size distribution during granules dissolution proved to be a useful tool for the understanding of dissolution mechanisms and for identifying non-uniformities of process conditions that can occur during scale-up., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The rising demands on discriminatory and prediction abilities of dissolution methods and the increasing complexity of new drug products are the main driving forces of the progress in this field. The research moves forward as imperfections and shortcomings of classical methods are being described, and where the capabilities of the contemporary methods are insufficient, new methods are being developed. The review discusses these advances with respect to the issues that currently draw the most attention, i.e. correct simulation of hydrodynamics and stress forces, maintenance of sink conditions, study of precipitation, use of biorelevant media and the employment of more physiologically relevant methods in general.

Development of new pharmaceutical compounds and dosage forms often requires in vitro dissolution testing with the closest similarity to the human gastrointestinal (GI) tract. To create such conditions, one needs a suitable dissolution apparatus and the appropriate data on the human GI physiology. This review discusses technological approaches applicable in biorelevant dissolutions as well as the physiology of stomach and small intestine in both fasted and fed state, that is, volumes of contents, transit times for water/food and various solid oral dosage forms, pH, osmolality, surface tension, buffer capacity, and concentrations of bile salts, phospholipids, enzymes, and Ca(2+) ions. The information is aimed to provide clear suggestions on how these conditions should be set in a dynamic biorelevant dissolution test., (Copyright © 2013 Wiley Periodicals, Inc.)