Dissolution testing medium selection

The first step in the development of a new dissolution test is to evaluate the relevant physical and chemical data for the drug substance. Knowledge of the drug compound s physical-chemical properties will facilitate the selection of dissolution medium and determination of medium volume. 

The medium selected for the dissolution test must consider the drug solubility. Aqueous media with a typical plT range between 1 and 7 to mimic the human gastrointestinal tract are preferred over organic solvents. The operating parameters of the dissolution setting should be optimized to ensure complete dissolution. ... 

The choice of dissolution medium will depend on the purpose of the dissolution test. For batch-to-batch quality control testing, selection of the dissolution medium is based, in part, on the solubility data and the dose range of a drug product to ensure that sink conditions are met. However, under certain circumstances, a medium that fails to provide sink conditions may be justiLable [8], If the... 

This is the place to start, since most often, analytical chemists are trying to help solve someone else s problem. We need to define the solute and its matrix as well as the nature of the analytical problem. For example, in the world of pharmaceuticals, there are raw material identification and purity determinations, in-process testing, dosage-form determinations, content uniformity, dissolution testing, stability studies, bioavailability, pharmacokinetics, and drug metabolism, to name a few. Each of these analytical problems has its own specific requirements. The matrix can be a raw material, granulation, tablet, capsule, solution, lotion, cream, syrup, dissolution medium, blood serum, urine, or various body tissues and fluids. Similar definitions can be described for virtually any industrial area and problem set. These definitions will help select sample preparation, separation, and detection techniques. 

For batch-to-batch quality testing, selection of the dissolution medium is based, in part, on the solubility data and the dose... 

Generally, the objective is to select a medium in which sink conditions are maintained so that the drug already in solution does not exert a modifying effect on the dissolution of the remaining drug. For low solubility drugs it may not be possible to achieve sink conditions, and so it may be preferable to test formulations of these drugs under nonsink conditions that accurately reflect the in vivo situation. 

In mutagenesis the main condition of success is the development of a sensitive and rapid method of mutant selection. Vitamin B12 production by propionic acid bacteria correlates with acid production. But the method of selection based on picking colonies with the maximal diameter of dissolution zones of calcium carbonate (added to solid medium) did not give positive results, since the size of colonies is not identical while acid production is dependent on the quantity of biomass. Selection based on the intensity of pink color that correlates with vitamin B12 production has a disadvantage in that selection of small mutations is made step by step, when differences in color can hardly be noticed by eye. Another method used was based on direct determination of vitamin B12 in single colonies. This method is labor-intensive and severely limits the testing of large numbers of colonies. 

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