Concepts of Similarity and �Difference factors

Introduction to Concepts of Similarity and Difference factors,
Importance of dissolution profile comparison,
Objective of dissolution profile comparison,
Method to compare dissolution profile , f1 & f2 Comparison
Presented By
N. Poojitha
Department of Pharmaceutics

1. 1 Concepts of Similarity and Difference factors A Seminar as a part of curricular requirement for I year M. Pharm I semester Presented by N. POOJITHA (Reg. No. 20L81S0308 ) Under the guidance Dr . CH Pavan Kumar M.Pharm, Ph.D. Associate Professor, Head Dept. of Pharmaceutics

2. 2 Introduction Importance of dissolution profile comparison Objective of dissolution profile comparison Method to compare dissolution profile f1 & f2 Comparison Applications References References Contents

3. 3 Introduction   Definition: It is graphical representation [in terms of concentration vs. time] of complete release of drug from a dosage form in an appropriately selected dissolution medium. That is in short it is the measure of the release of A.P.I from a dosage form with respect to time.

4. 4 Dissolution profile of an A.P.I. reflects its release pattern under the selected condition sets. FDA has placed more emphasis on dissolution profile comparison in the field of post approval changes. The most important application of the dissolution profile is that by knowing the dissolution profile of product of the BRAND LEADER, we can make appropriate necessary change in our formulation to achieve the same profile of the brand leader. Importance of dissolution profile Comparison

5. 5 Objective of dissolution profile Comparison To Develop in-vitro in-vivo correlation which can help to reduce costs, speed-up product development and reduce the need to perform costly bioavailability human volunteer studies. Establish the similarity of pharmaceutical dosage forms, for which composition, manufacture site, scale of manufacture, manufacture process and/or equipment may have changed within defined limits.

6. 6 METHODS TO COMPARE DISSOLUTION PROFILE  

7. 7 Similarity and difference factors f1 and f2

8. 8   DIFFERENCE FACTOR (f1) & SIMILARITY FACTOR (f2)

9. 9  

10. 10 Difference factor Similarity factor inference 100 Dissolutions profile are similar ≤15 ≥50   Similarity or equivalence of two profiles Limits for similarity and Difference factors  

11. 11 Data structure and steps to follow:  This model-independent method is most suitable for the dissolution profile comparison when three to four or more dissolution time points are available. Determine the dissolution profile of two products (12 units each) of the test (post-change) and reference (pre-change) products. Using the mean dissolution values from both curves at each time interval, calculate the difference factor (f1) and similarity factor (f2) using the above equations.

12. 12 For curves to be considered similar, f1 values should be close to 0, and f2 values should be close to 100. Generally, f1 values up to 15 (0-15) and f2 values greater than 50 (50-100) ensure sameness or equivalence of the two curves and, thus, of the performance of the test (post-change) and reference (pre- change) products. In dissolution profile comparisons, especially to assure similarity in product performance, the regulatory interest is in knowing how similar the two curves are, and to have a measure which is more sensitive to large differences at any particular time point. For this reason, the f2 comparison has been the focus in agency guidance and used to make a decision.

13. Some recommendations: The dissolution measurements of the test and reference batches should be made under exactly the same conditions. The dissolution time points for both the profiles should be the same (e.g. 15, 30, 45, 60 minutes). The reference batch used should be the most recently manufactured pre-change product.

14. 14 Only one measurement should be considered after 85% dissolution of both the products (when applicable). To allow use of mean data, the percent coefficient of variation (% CV) at the earlier time points (e.g. 15 minutes) should not be more than 20%, and at other time points should not be more than 10%. The mean dissolution values for reference can be derived either from last pre-change batch or the last two or more consecutively manufactured pre-change batches.

15. 15 This method is more appropriate when more than three or four dissolution time points are available. The f2 may become invariant with respect to the location change and the consequence of failure to take into account the shape of the curve and the unequal spacing between sampling time points lead to errors. Nevertheless, with a slight modification in the statistical analysis, similarity factor would definitely serves as an efficient tool for reliable comparison of dissolution profiles.  Nevertheless, with a slight modification in the statistical analysis, similarity factor would definitely serves as an efficient tool for reliable comparison of dissolution profiles.   Applications

16. 16 Advantages : They are easy to compute. 2. They provide a single number to describe the comparison of dissolution profile data . Disadvantages : The values of f1 and f2 are sensitive to the number of dissolution time points used. The basis of the criteria for deciding the difference or similarity between dissolution profile is unclear  

17. 17 Hussain L, Ashwini D, Sirish D. Kinetic modelling and dissolution profiles comparison: an overview. Int J Pharm Bio Sci. 2013; 4(1): 728 - 737. Thomas O’H, Adrian D, Jackie B and John D. A review of methods used to compare dissolution profile data. PSTT. 1998; 1(5): 214-223. Dissolution, bio avaibility and bioequivalence by Hamed M. Abdou. The theory and practice of industrial pharmacy by Lachmann Liberman. Biopharmaceutics and pharmacokinetics by D.M. Bhramankar and Sunil b. Jaiswal References

18. 18 Thank you