Purpose To describe the properties of the similarity factor (f2) as a measure for assessing the similarity of two dissolution profiles Discuss the statistical properties of the estimate based on sample means 
Methods The f2 metrics and the decision rule is evaluated using examples of dissolution profiles The confidence interval is calculated using bootstrapping method The bias of the estimate using sample mean dissolution is evaluated 
Results 1 f2 values were found to be sensitive to number of sample points, after the dissolution plateau has been reached 2 The statistical evaluation of f2 could be made using 90% confidence interval approach 3 The statistical distribution of f2 metrics could be simulated using 'Bootstrap' method A relatively robust distribution could be obtained after more than 500 'Bootstraps' 4 A statistical 'bias correction' was found to reduce the bias 
Conclusions The similarity factor f2 is a simple measure for the comparison of two dissolution profiles But the commonly used similarity factor estimate ^f2 is a biased and conservative estimate of f2 The bootstrap approach is a useful tool to simulate the confidence interval

In Vitro Dissolution Profile Comparison—Statistics and Analysis of the Similarity Factor, f2

Contributors Jean-Marc Aiache, Nobuo Aoyagi, Dennis Bashaw, Cynthia Brown, William Brown, Diane Burgess, John Crison, Patrick DeLuca, Ruzica Djerki, Jennifer Dressman, Thomas Foster, Kirsti Gjellan, Vivian Gray, Ajaz Hussain, Tom Ingallinera, James Klancke, Johannes Kraemer, Henning Kristensen, Kofi Kumi, Christian Leuner, Jobst Limberg, Petra Loos, Lenny Margulis, Patrick Marroum, Helga Moeller, Bernd Mueller, Martin Mueller-Zsigmondy, Ngozi Okafo, Larry Ouderkirk, Shravan Parsi, Saeed Qureshi, Joseph Robinson, Vinod Shah, Martin Siewert, Ramana Uppoor, and Roger Williams. Aventis, Frankfurt, Germany JW Goethe University, Frankfurt, Germany Eli Lilly and Company, Indianapolis, IN Office of Pharmaceutical Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Rockville, MD Universite d'Auvergne, Clermont-Ferrand Cedex, France National Institute of Health Sciences, Division of Drugs, Tokyo, Japan US Pharmacopeia, Rockville, MD University of Connecticut, Storrs Mansfield, CT Pfizer, Inc, La Jolla, CA University of Kentucky, Lexington, KY Novartis Pharma, Basel, Switzerland AstraZeneca, Sodertalje, Sweden V.A. Gray Consulting, Inc, Hockessin, DE AAI International, Charleston, SC CIMA Laboratories, Inc, Minneapolis, MN Laboratory and Quality Services, Eschborn, Germany University of Copenhagen, Denmark Bundesinstitut fur Arzneimittel, Bonn, Germany Aventis Pharmaceuticals, Bridgewater, NJ Pfizer, Groton, CT Zentrallaboratorium Deutscher Apotheker, Eschborn, Germany Kiel University, Kiel, Germany Alza Corporation, Mountain View, CA DPT Laboratories, Ltd, San Antonio, TX Health Protection Branch, Ottawa, Canada University of Wisconsin, WI

/pdf/fip-aaps-guidelines-to-dissolution-in-vitro-release-testing-2cp52c25iq.pdf

FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms

In vitro models for the prediction of in vivo performance of oral dosage forms

https://era.library.ualberta.ca/items/36f7f046-2e47-4138-b69b-00eeac6f5792/view/144407f8-44b6-4b04-9762-b561c587100a/Azarmi-20dissolution-20perspectives.pdf

Current perspectives in dissolution testing of conventional and novel dosage forms

This review summarizes the methods used to study real-time (37°C) drug release from nanoparticulate drug delivery systems and establish an IVIVC. Since no compendial standards exist, drug release is currently assessed using a variety of methods including sample and separate (SS), continuous flow (CF), dialysis membrane (DM) methods, and a combination thereof, as well as novel techniques like voltametry and turbidimetry. This review describes the principle of each method along with their advantages and disadvantages, including challenges with set-up and sampling. The SS method allows direct measurement of drug release with simple set-up requirements, but sampling is cumbersome. With the CF method, sampling is straightforward but the set-up is time consuming. Set-up as well as sampling is easier with the DM, but it may not be suitable for drugs that bind to the membrane. Novel methods offer the possibility of real-time drug release measurement but may be restricted to certain types of drugs. Of these methods, Level A IVIVCs have been obtained with dialysis, alone or in combination with the sample and separate technique. Future efforts should focus on developing mathematical models that describe drug release mechanisms as well as facilitate formulation development of nano-sized dosage forms.

/pdf/a-review-of-in-vitro-drug-release-test-methods-for-nano-2hkq6qa2px.pdf

A Review of In Vitro Drug Release Test Methods for Nano-Sized Dosage Forms

/pdf/fda-guidance-for-industry-1-extended-release-solid-oral-4uj9fwkeu8.pdf

FDA Guidance for Industry 1 Extended Release Solid Oral Dosage forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations

This draft guidance provides recommendations to pharmaceutical scientists related to various aspects of in vitro/in vivo correlations (IVIVC) for oral extended-release (ER) drug products particularly as utilized in the NDA/ANDA review process It presents a comprehensive perspective on methods of developing IVIVC, appropriate means of evaluating the predictability of IVIVC, and relevant applications for IVIVC in the areas of changes (eg, formulation, equipment, process, and manufacturing site) and setting dissolution specifications To access the final guidance on the WWW, connect to theFDA home page at http://wwwfdagov/CDER/ and go to the “Regulatory Guidance” section

Kofi Kumi

Papers

FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms

FDA Guidance for Industry 1 Extended Release Solid Oral Dosage forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations

Draft Guidance for Industry Extended-Release Solid Oral Dosage Forms