1	Application of the Sotax AT70smart within a development laboratory Dónal J Murphy PhD Analytical Development AstraZeneca UK
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3	Overview Method Transfer Considerations Tablet drop Temperature differential Filters Automated media preparation Equivalence with manual method Examples of system application
4	Method Transfer Considerations Tablet drop Successful automatic tablet drop can be influenced by tablet shape and dimensions Correct choice of tablet magazine will ensure successful drop Tablet magazines of varying hole dimensions are available
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6	Method Transfer Considerations Temperature Differential Standards and samples are not at the same temperature (using standard equipment) Potential for spectral effects Check for differences in lmax and Abs Apply thermal control if necessary
7	Method Transfer Considerations Cleaning Validation Need to ensure cleaning is adequate to prevent carryover Perform run using max dose followed by blank run Cleaning uses water only Possible issues for water insoluble drugs/excipients Media containing surfactants – also need to ensure adequate removal of surfactant
8	Method Transfer Considerations Filters Standard configuration works best with 25mm Acrodisc syringe filters (Pall Gelman) Choice of filter limited by back pressure Glass fibre and GHP work well Maximum number of unattended runs limited by number of filters required per run Could one filter be used for all timepoints?
9	Example
10	Method Transfer Considerations Automated Media Preparation Optional extra Prepares by dilution from concentrate (x10) pH accuracy of ± 0.05 pH units required Validate and verify Consider pH monitoring option Consider temperature effect
11	Method Transfer Considerations Equivalence with manual method How many batches to test? How many tablets to test? Are results comparable? Accuracy Precision What statistical tool(s) to use? Evidence of bias?
12	example: method 1
13	example: method 2
14	Sotax versus manual Analysis of difference Does equivalence hide potential problems? Is hollow shaft sampling an issue? Do different filters have an effect? Sampling & filtration effects? Traditional sampling position – do resident cannulae have an effect?
15	Analysis of Difference
16	Analysis of Difference
17	Analysis of Difference
18	Analysis of Difference
19	Analysis of Difference
20	Analysis of Difference
21	Analysis of Difference - Summary
22	Applications What do we use the system for? Clearances Stability samples Development runs (method and formulation) Where long runs times are required (e.g. data for IVIVC) Investigations where greater precision is required
23	example: Data for IVIVC
24	example: Investigation of small differences
25	Acknowledgements