Comparison of dissolution profile of extendedrelease oral. May it be used beyond simple supuc change as proposed. This sampling time was necessary because sensitivity to dissolution variables typically appears midway through the dissolution profile. Decision tree for dissolution profile comparison 2018 asa regulatoryindustry statistics workshop sept.
The dissolution time points for both the profiles should be the same. In 1996, moore and flanner proposed two indices, or fit factors, to compare dissolution profiles in a pairwise fashion. Agilent dissolution seminar series welcome agilent dissolution. For optimizing the dosage formula by comparing the dissolution profiles of various formulas of the same a. Model dependent and model independent approaches similarity in dissolution behavior of drugs has long been. F1 and f2 factor calculation factor of difference and similarity.
The similarity factor fits the result between 0 and 100. Where 85% of the drug is dissolved within 15 min, dissolution profiles may be accepted as similar without further mathematical evaluation. Is there any method to use when the sampling time of two profiles are different. Dissolution profile comparisondissolution profile comparison using similarity factor, f2 vinod p. Guidelines on dissolution profile comparison gudrun. In vitro dissolution profilein vitro dissolution profile comparisonstatistics and analysis of the similarity factor. Results the dissolution profiles of the formulations are. Pdf modeling and comparison of dissolution profiles. Customization of the dissolution profile comparison tests for er formulations was possible by using the tdt without sacrificing its statistical properties known and acceptable statistical uncertainty. This method is more adequate to dissolution profile comparisons when more than three or four dissolution time points are available. Msd tests can be performed either on raw data with or without time as a variable or on. Comparison of in vitro dissolution tests for commercially available aspirin tablets fawzia khan, mingzhong li, and walkiria schlindwein.
A critique of current practice dave leblond1, stan altan2. The single sampling time chosen for comparison of repeatability was the period at which about 4060% of the drug dissolved see table i. In order to consider the similar dissolution profiles, the f 1 values should be close to 0 and values f 2 should be close to 100. Similar dissolution profile is in general considered as an assurance of product sameness and product performance in the presence of scaleup and supac changes.
Very often, an in vitro dissolution test is more sensitive and discriminating than an in vivo test. A profile comparison is not necessary for products that are rapidly dissolving i. The food and drug administration fda is announcing. In cases of high variability, the f 2 test is not applicable, and the multivariate statistical distance msd test is frequently proposed as an alternative by the fda and ema. Is there any approach with better statistical properties. Dissolution comparisons using a multivariate statistical. For ir formulations, comparison at 15 min is essential to know if complete dissolution is reached before gastric emptying. Two different methods of dissolution profile comparison were used. To waive bioequivalence requirements for lower strengths of a dosage form. The proposed model is shown to be useful in assessment of similarity between dissolution profiles of two drug products.
Comparison of dissolution profile of extendedrelease oral dosage forms two onesided equivalence test 369 dissolution test of extendedrelease dosage forms as a basis. But the commonly used similarity factor estimate f 2 is a biased and conservative estimate of f2. A comparative study of the invitro dissolution profiles of paracetamol and caffeine combination, y. In vitro dissolution profile comparisonstatistics and. The quantitative analysis of the values obtained in dissolutionrelease tests is easier when mathematical formulas that express the dissolution results as a function of some of the dosage forms characteristics are used. Modeling and comparison of dissolution profiles pdf. In vitro dissolution testing usually must be performed as comple mentary to the in vivo bioavailability investi gations. The f 2 test is generally used for comparing dissolution profiles. The applied methods for the comparison of in vitro dissolution profiles are. The most important application of the dissolution profile is that by knowing the dissolution. Guidelines on dissolution profile comparison sage journals.
Pdf to describe the properties of the similarity factor f2 as a measure for assessing the similarity of two dissolution profiles. A comparative study of the invitro dissolution profiles. The pharmaceutical industry and the registration authorities do focus, nowadays, on drug dissolution studies. Dissolution profile comparisons are used in the context of postapproval changes where the manufacturer has to demonstrate that the quality of the product is. Microscopic comparison in identical scale show the jp basket with. The dissolution profiles of oxycodone extended release tablets containing 10 mg, 20 mg and 40 mg reference and generic were evaluated according to the. In this context, the guidelines on in vitroin vivo correlations and on granting biowaivers are outlined briefly. Pdf to develop and propose a model dependent approach for the invitro dissolution profiles comparison. Hydrodynamic investigation of usp dissolution test. These factors, proposed by moore and flanner 1996, are specific models for the comparison between the profiles. Office of pharmaceutical qualityoffice of new drug products. To develop and propose a model dependent approach for the invitro dissolution profiles comparison.
Importance of dissolution profile fda has placed more emphasis on dissolution profile comparison in the field of post approval changes and biowaivers e. Pdf in vitro dissolution profile comparisonstatistics and. However, finding a method to assess similarity between two. Zayed abstract dissolution testing is an in vitro technique of great importance in formulation and development of pharmaceutical dosage forms, as it. For example, the fda scaleup and postapproval changesmodified release supacmr guidance indicates that similar. Decision tree for dissolution profile comparison in product quality. This indicated they may be treated as similar to brand 1 for the dissolution comparison at the. Diltiazem hydrochloride tablet dissolution profiles were compared using a statistical approach. Dissolution test for solid dosage forms european pharmacopoeia 6. Diltiazem hydrochloride tablet dissolution profiles were compared using a statistical approach based on a mathematical model.
The guidelines provide only general recommendations. For the comparison of dissolution profiles, similarity factor. In general, f 1 values lower than 15 015 and f 2 values higher than 50 50100 show the similarity of the dissolution profiles. Comparisons of dissolution profiles of the different brands were carried out. Class i drugs of bcs classification are skipped off these testing for quicker approval by fda. A simple approach for comparing the in vitro dissolution. Comparison of dissolution profiles of theophylline extendedrelease dosage forms 85 ference factor and f2 similarity factor were used to compare the obtained dissolution profiles. Dissolution testing of immediate release solid oral dosage forms august 1997. From a quality assurance point of view, a more discriminative dissolution method is preferred, because the test will indicate possible changes in the quality of the product before. The model developed by moore and flanner is used to compare the dissolution profile using two factors, f1 and f2 1 following the fda guidance for comparing the dissolution profiles 2, 3.
The dissolution profile for solid pharmaceutical forms containing chloramphenicol 250 mg available in brazil was determined using a method from the american pharmacopoeia united states pharmacopoeia, 2004 and then compared. The dissolution measurements of the test and reference batches should be made under the same conditions. A dissolution profile comparison between prechange and postchange products for scaleup and post approval change supac related changes, or with different strengths helps assure similarity in. Dissolution profiles may be considered similar by virtue of overall profile similarity and similarity at every dissolution sample time point. Bioequivalence testing, using the dissolution profile. General dissolution profile equation for no replacement if this is your first visit, be sure to check out the faq by clicking the link above. Pdf comparison of in vitro dissolution profiles by anovabased. Dissolution profile evaluation of solid pharmaceutical. General dissolution profile equation for no replacement.
Dissolution test is one of the most valuable in vitro tests used to assure the drug product quality. The similarity factor f 2 is a simple measure for the comparison of two dissolution profiles. Results and discussion the dissolution profile of oxycodone extendedrelease tablets containing 40 mg, 20 mg and 10 mg is shown in figure 1. In vitro dissolution profilein vitro dissolution profile comparison statistics and analysis of the similarity factor. Comparison of dissolution profile by model independent. Pdf dissolution profile comparison using similarity. The following recommendations should alsom be considered. Dissolution profiles are considered similar if the calculated. When in vitro dissolution profile variability prohibits the use of the f2 metric, there currently is no satisfactory alternative available. Emas current practice and challenges in the evaluation of. For accepting product sameness under supacrelated changes.
The dissolution profile was also analyzed by applying factors difference factor and similarity factor, setting randomly one of the batches of each dosage 5 mg. Comparison of in vitro dissolution tests for commercially. Dissolution profile comparison between pre change and post. Euphyllin long 300 was a reference product and calculations were performed according to fda guidelines. The therapeutic goods administration is part of the health products regulation group. Guidelines on dissolution profile comparison gudrun freitag, 2001. Dissolution testing of immediate release solid oral dosage.
The dissolution profile comparison can be conducted using modelindependent or modeldependent statistical methods. The bootstrap approach is a useful tool to simulate the confidence interval. Within veterinary medicine, an additional complication is the. In a number of recent guidance documents, the fda has placed more emphasis on the meaningful comparison of dissolution profile data. Published reports evaluating alternative approaches such as multivariate statistical distance and use of a bootstrap f2 identify sources of bias that can limit the utility of these alternatives.