Segregation leading to drop in thiamine content during solid-solid mixing

Purpose: The study aims at solving drop in assay value of thiamine hydrochloride in freshly made Vitamin B Complex tablet formulation despite incorporation of 15% over the label claim. Unaccounted results are always a matter of concern in the pharmaceutical industry. The study also aims at identifying a general procedure for the determination of optimum mixing time and suitable mixing machines for low strength active ingredients incorporated with dried granules in a similarly manner.

 

Methods: Rigorous evaluation of the entire manufacturing procedure pointed to a possible segregation as the cause. Three types of mixing machines representing convective, diffusion and shear mixing were investigated. Graphs were drawn using standard deviation (S), variance (S2) and Lacey Mixing Index derived mixing scales – ln (S2/ S02) of the thiamine content against accumulated mixing times.

 

Results: According to the curves obtained optimum mixing was found to be around 5 minutes for all three types of machines. The drum mixer showed the lowest variance indicating best homogeneity of the blend.

 

Conclusion: The arbitrarily perceived safe mixing for 15 minutes had been counterproductive leading to segregation of thiamine. Reducing both the mixing time and the 15% overage of thiamine can still improve the assay towards the expected theoretical value.