« DISSOLUTION
These results do not disagree with the previous ones. The BE between the two products means similar rate and amount absorbed in vivo, which could probably be due to the high in vitro dissolution rate found for both products (>85% in 30 minutes, highlighted in grey in Figure 2). That is, the differences detected by the f2
factor
were not biorelevant due to the rapid dissolution in water of the products, being more suitable the comparison of AUC and DE.
Concluding Remarks
This brief review has attempted to provide a comprehensive overview of the advantages and disadvantages of the main methods available to compare dissolution profiles in situations where comparisons are aimed to assess the in vitro biopharmaceutical performance of multisource products in order to ensure similar in vivo performance of the products, as in the case of biowaivers [1, 6].
Results illustrated that MIM are the most suitable for profiles comparison in such situations. ASM are not adequate to the dissolution experimental data processing. MDM are over- discriminating and not easy to calculate, with the additional disadvantage of requiring fitting the data to some descriptive equation, which makes them unsuitable for the comparison of dissolution profiles of multisource drug products that do not fit to the same model, as occurred with CBZ and ACM results.
Therefore, when the biopharmaceutical quality of multisource drug products are to be compared through in vitro dissolution studies, the current recommended method (similarity factor, f2
)
is adequate, although it may be insufficient or its interpretation ambiguous in certain situations. A recent study by Duan et al. analyzed the correspondence between the f2
and in vivo results
obtained by simulations, and concluded that although the results were consistent in most cases, care should be taken when the completeness of the dissolution profiles differ more than 10% and/ or when the shapes of the dissolution profiles are significantly different [15].
These ambiguous situations, as well as the extreme sensitivity of the f2
factor to the first, and sometimes not critical, points of the
dissolution profiles lead us to the main conclusion, which is always inform the result of AUC or DE comparison along with the f2
factor.
By doing so, a better prediction of in vivo performance could be achieved in terms of both rate and amount of drug dissolved, which is the ultimate goal when comparing multisource and potentially therapeutic equivalents.
Moreover, these simple calculations do not require specific software or training, and they may become a robust tool in establishing the similarity between dissolution profiles, particularly in those situations where the f2
value is near the specification (50) or when
is greater or less than 50 depending on which product is taken as the reference for the calculation.
12. 13. 14. 15. 6.
7. 8.
9.
Author Biography
Esperanza Ruiz, Ph.D., obtained her degree of Pharmacist and Licentiate in Pharmaceutical Sciences from the National University of La Plata, Argentina, receiving two awards for academic excellence. Esperanza holds a Ph.D. degree from the same University, where she currently works as a full time researcher and teaches Quality Control of Medications and Experimental Design. Her scientific contributions comprise over 30 publications, including journal articles and presentations in conferences and meetings.
References 1.
2. 3. 4. 5.
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