After oral administration of a solid formulation, drug absorption depends on dissolution or release of the drug, dissolution of the drug under physiological conditions, and penetration into the gastrointestinal tract. Dissolution curves are continuous measurements of drug release at a series of time points. When the release degree of the drug reaches the requirement or the release platform, a smooth curve can be drawn according to the time-dissolution degree, which expresses the behavior of drug release over time. For common oral solid formulations, generic drug quality can be evaluated by comparing the similarity of multiple dissolution curves in vitro between generic drugs and RLD.
Methods for comparing dissolution curve similarity include model-dependent and non-model-dependent methods. The main model dependence methods are Weibull's distribution and the Higuchi model. Non-model-dependent methods include one-way ANOVA, the similarity factor method, Chow and Ki's method and the AV method. The similarity factor f2 is recognized by regulatory authorities in many countries, is relatively easy to calculate, and is also the most common indicator to evaluate dissolution curve similarity.
Our Services
As a well-regarded generic drugs services company, Alfa Chemistry provides bioequivalence evaluation services for generic drugs companies, covering in vitro dissolution studies. In addition to developing and validating dissolution methods, we also perform the dissolution curve similarity comparison. Since the in vitro dissolution versus time curve involves a lot of data processing and formula use, working with our experienced team will greatly simplify your generic drug research process and accelerate your product to market.
The f2 similarity factor is a reference value for evaluating the similarity of average dissolution curves between generic drugs and RLD under the same dissolution conditions, which can scientifically and reasonably reflect the dissolution behavior of oral solid preparations in vitro and has certain significance for judging their bioavailability and bioequivalence in vivo.
FDA and EMA have established clear acceptance criteria for f2 similarity factors, and the relevant requirements are basically the same. Our company mainly uses the f2 similarity factor method to compare the similarity of dissolution curves between generic drugs and RLD, which is most suitable in the case of 3-4 or more sampling points. When the customer's dissolution curve cannot be compared by this method, we can use other suitable comparison methods and fully demonstrate their use.
Conditions for dissolution similarity comparison
Our trial is designed and conducted in compliance with regulatory regulations, and our dissolution similarity comparison meets the following conditions:
- Using the same dosage form, the same specifications as the preparation
- The dissolution curves of generic drugs and RLD are determined under exactly the same conditions
- The sampling points for generic drugs and RLD dissolution curves are the same
- RLD and generic drugs must simultaneously exceed 85% dissolution, or reach the asymptote
- At least three time points
- Using the average value, the RSD of dissolution at the earliest time point should not be greater than 20%, and the RSD of dissolution at other time points should not be greater than 10%.
- The average amount of dissolution is generally the average of 12 pieces (particles).
Criteria for determining the similarity of dissolution curves
- In general, when the similarity factor (f2) value of two dissolution curves is not less than 50, the dissolution curves can be considered similar.
- The dissolution curves can be considered similar when neither generic drug nor RLD has a mean dissolution of less than 85% at 15 minutes.
