Dissolution testing experimental design

All apparatus must be calibrated and the variables standardized and known. Experimental design in dissolution testing to examine residual variation between experimental runs and individual dissolution vessels is feasible. The objective is to minimize errors in experimental set-up, achieved by using mean dissolution times and partial balancing. Lower coefficients of variation occur at higher hydrodynamic intensities. 

Worksheet illustrating a statistical experimental design for evaluating the effect on the dissolution of variations of the test conditions in an in vitro dissolution method. 

The variable X3 takes 3 levels, so it was chosen to correspond to the stirring rate. The normal rate for the dissolution testing of the formulation was 75 rpm, and the extremes to be tested were 75 25 rpm. The coded levels 0.866 correspond therefore to 50 and 100 rpm. (It would also have been possible to set the levels 1 to 50 and 100 rpm, in which case the levels coded 0.866 would have corresponded to 53 and 97 rpm.) If each experiment were carried out twice, these experiments could be done in two dissolution runs. We assume here that the run to run reproducibility is sufficiently good. There remain 7 experiments at the level zero of stirring speed (75 rpm). These experiments also were carried out in duplicate. This allowed the whole experimental design to be carried out using only 4 dissolution runs as shown in table 5.23. 

Experimental design - describes the procedure that will be followed including the number of batches, replicates, analysts, instruments, and any additional detail that may not be covered in the method but is critical to the transfer such as sample and standard preparation, number of injections for each as well as how many samples can be injected between standards, dissolution de-aeration procedure, time frame for completing all testing once the samples are received, such as 30 days. 

Since water is the reactant in equation (1), the diffusion should be important only in removing the products from the reaction zone. The measurements presented in the Experimental Results Section were designed to determine the relative effects of the surface reaction rate and the diffusion of products on the overall dissolution rate. The variables in these tests were temperature, pH, stirring rate, and type of limestone. 

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