Small Volume Dissolution Testing as a Powerful Method during Pharmaceutical Development.

Emmanuel Scheubel,Marc Lindenberg,Jean-Michel Cardot,Eric Beyssac

doi:10.3390/pharmaceutics2040351

Emmanuel Scheubel, Marc Lindenberg + Show 2 more

Open Access

https://doi.org/10.3390/pharmaceutics2040351

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Abstract

Standard compendia dissolution apparatus are the first choice for development of new dissolution methods. Nevertheless, limitations coming from the amount of material available, analytical sensitivity, lack of discrimination or biorelevance may warrant the use of non compendial methods. In this regard, the use of small volume dissolution methods offers strong advantages. The present study aims primarily to evaluate the dissolution performance of various drug products having different release mechanisms, using commercially available small volume USP2 dissolution equipment.The present series of tests indicate that the small volume dissolution is a useful tool for the characterization of immediate release drug product. Depending on the release mechanism, different speed factors are proposed to mimic common one liter vessel performance. In addition, by increasing the discriminating power of the dissolution method, it potentially improves know how about formulations and on typical events which are evaluated during pharmaceutical development such as ageing or scale–up. In this regard, small volume dissolution is a method of choice in case of screening for critical quality attributes of rapidly dissolving tablets, where it is often difficult to detect differences using standard working conditions.

Highlights

Dissolution testing is a core performance test in pharmaceutical development and quality control.Dissolution testing has more and more evolved to establish relationships with in vivo performance or with manufacturing Critical Quality Attributes (CQA) in the scope of Quality by Design (QbD)[1]..The overall goal is to better control product performance within the life cycle of a product
The present study aims primarily to evaluate the potential of commercially available small volume
No coning or mounting was observed using the small volume vessel except for the prednisone disintegrating tablets, which was seen for the one liter vessel

Summary

Introduction

The overall goal is to better control product performance within the life cycle of a product For this purpose, the use of the classical USP dissolution working conditions using a one liter vessel with basket (respectively USP1) and paddle (respectively USP2) are well established [2,3] and are used as the first choice for development of a new dissolution method. In early phase development, during screening of drug candidates, formulation is often developed for studies in animals and dissolution should be ideally conducted using media simulating the gastrointestinal environment as well as in volumes in line with the animal physiology [4] Another case in which a classical method is not well suited is for low dose drugs or if the analytical method is not sensitive enough to detect the amount of dissolved drug precisely due to low concentration of the drug in the formulation [5]. To overcome those problems the concept of small-volume dissolution arose recently due to the possibility of using smaller sample sizes and smaller volumes of media, offering various advantages in view of substance and material consumption [6] and can serve as a valuable tool for dosage form screening [7] or formulation selection in animals

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