MATHEMATICAL APPROACH FOR THE ASSESSMENT OF SIMILARITY FACTOR USING A NEW SCHEME FOR CALCULATING WEIGHT

The objective of the present work was to propose a method for calculating weight in the Moore and Flanner Equation. The percentage coefficient of variation in reference and test formulations at each time point was considered for calculating weight. The literature reported data are used to demonstrate applicability of the method. The advantages and applications of new approach are narrated. The results show a drop in the value of similarity factor as compared to the approach proposed in earlier work. The scientists who need high accuracy in calculation may use this approach.


The New Scheme for Calculating Weight
The new scheme for calculating weight shows impact of within sample variability on f2 value. Weight (wt) is calculated using equation 2. Where, wt is weight, %CV of Rt and %CV o f T, are the percentage coefficient of variation of reference and test products respectively. MCVe/l is the maximum allowable % CV. MCVe/l was 20 for earlier time point (30 min) and it was 10 for later time points (above 30 min). Co-efficient of variation was calculated using the following equation 3.

Mean
If the %CV of R, and %CV of Tt is equal to zero, wt is equal to one.

Determination of Similarity Factor for Formulated Dosage Forms.
Three formulations (A, B and C) were prepared. Formulation A was capsule containing two floating tablet of rifampicin plus one enteric coated isoniazid capsule. Formulation B was a capsule containing floating minimatrices o f rifampicin plus enteric minitablets of isoniazid. Formulation C was made up of gastro-retentive minitablets of rifampicin plus enteric sustained release microcapsules of isoniazid. The in vitro drug release profile of these formulations was utilized for calculating similarity factor. The in vitro drug release study was carried out by the method mentioned in chapter 5.  10. New Scheme for Calculating Weight f2-m was lower than the value of f2-ni3 in all the cases (test 1 to test 5). The new approach appears to be more sensitive than the approach 3 proposed in the earlier publication since within sample variability is incorporated in the new approach. :v of Tt, w, = 1 + (% CV o f R,/MCVe/l) + (% f2-m = Similarity factor calculated using new approach, f2.m3 = Similarity factor calculated using approach 3, f2 = Similarity factor calculated using conventional method (wt =1) Table 10.4 displays the value of similarity factor calculated using the new approach (f2m) and approach 3 (f2-ni3) of our earlier publication. The results shows that the value of f2-m was lower than the value of f2-m3 in all the cases (test 1 to test 5). The new approach appears to be more sensitive than the approach 3 proposed by Gohel and co- In the new scheme of weight (w,) calculation, no parameter was decided on an arbitrary ground. The new approach appears to be more realistic as compared to approach 3.
Another advantage of the new method is simple calculation steps than approach 3. Equal stress is given to variability in reference and test formulation in the new approach. The maximum allowable %CV, as proposed in FDA guidance document, is also considered in the proposed method. It considers within samples (12 units of reference and 12 units of test) as well as between samples (reference and test formulations) variability because of utilization of SD and averages of reference and test formulations at each time point for calculating weight. 10. New Scheme for Calculating Weight considered as similar. The similarity factor of formulations A, B and C decreased significantly the new scheme of calculating weight was adopted.

Conclusion
The use of new method is recommended in deciding equivalence of test product with innovators product. The approach may also find application in selection o f a bio-batch.
The use o f new approach may become a strong point in ANDA submission. If all the three yields f2 greater than 50 than we may safely assume that products show similar dissolution. The positive and negative points of the new approach will emerge out when various researchers will try the approach with their data sets.