In Vitro Studies , Dissolution Studies to Determine Bioequivalence and Bioavailability of a Drug
Under certain circumstances, product quality BA and BE can be documented using in vitro approaches (21 CFR 320.24(b)(5) and 21 CFR 320.22(d)(3)). For highly soluble, highly permeable, rapidly dissolving, and orally administered drug products, documentation of BE using an in vitro approach (dissolution studies) is appropriate based on the biopharmaceutics classification system.(see Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System ) This approach may also be suitable under some circumstances in assessing BE during the IND period, for NDA and ANDA submissions, and in the presence of certain postapproval changes to approved NDAs and ANDAs. In addition, in vitro approaches to documenting BE for nonbioproblem drugs approved before 1962 remain appropriate (21 CFR 320.33).

Dissolution testing is also used to assess batch-to-batch quality, where the dissolution tests, with defined procedures and acceptance criteria, are used to allow batch release. FDA recommend that dissolution testing is also used to
(1) provide process control and quality assurance, and
(2) assess whether further BE studies relative to minor postapproval changes be conducted, where dissolution can function as a signal of bioinequivalence. In vitro dissolution characterization is encouraged for all product formulations investigated (including prototype formulations),
particularly if in vivo absorption characteristics are being defined for the different product formulations. Such efforts may enable the establishment of an in vitro-in vivo correlation.

When an in vitro-in vivo correlation or association is available (21 CFR 320.24(b)(1)(ii)), the in vitro test can serve not only as a quality control specification for the manufacturing process, but also as an indicator of how the product will perform in vivo.  recommendations on the development of dissolution methodology, setting specifications, and the regulatory applications of dissolution testing:

(1) Dissolution Testing of Immediate Release Solid Oral Dosage Forms; and
(2) Extended Release Oral Dosage Forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations.

FDA recommend that the following information generally be included in the dissolution method development report for solid oral dosage forms:
For an NDA:
* The pH solubility profile of the drug substance
* Dissolution profiles generated at different agitation speeds (e.g., 100 to 150 revolutions per minute (rpm) for U.S. Pharmacopeia (USP) Apparatus I (basket), or 50 to 100 rpm for USP Apparatus II (paddle))

* Dissolution profiles generated on all strengths in at least three dissolution media (e.g.,pH 1.2, 4.5, and 6.8 buffer). Water can be used as an additional medium. If the drug being considered is poorly soluble, appropriate concentrations of surfactants are recommended.
It is recommended that the sponsor select the agitation speed and medium that provide adequate discriminating ability, taking into account all the available in vitro and in vivo data.
For ANDAs:
* For immediate-release drug products, FDA recommend that the appropriate USP method be submitted. If there is no USP method available, FDA recommend that the FDA method for the reference listed drug be used. If the USP and/or FDA methods are not available, FDA recommend that the dissolution method development report described above be submitted.
* For modified-release products, dissolution profiles using the appropriate USP method (if available) can be submitted. If there is no USP method available, FDA recommend that the FDA method for the reference listed drug be used. In addition, FDA recommend that profiles using at least three other dissolution media (e.g., pH 1.2, 4.5, and 6.8 buffer) and water be submitted.
It is recommended that dissolution data from three batches for both NDAs and ANDAs be used to set dissolution specifications for modified-release dosage forms, including extendedrelease dosage forms.


Do you know now this website has become a most popular and most referred website in pharmaceutical industry and pharmaceutical companies and pharmaceutical manufacturers from all over the world ,for almost all topics related to Pharmaceutical Manufacturing , Pharmaceutical Regulatory Affairs and Good Manufacturing Practice for Pharmaceutical Manufacturing (c GMP guidelines ) and latest news and new drugs developments.

You may also like following articles

Whar is Referance Listed Drug  ? ( RLD )

What is Pharmaceutical Equivalents

What is Pharmaceutical Alternatives

What is Therapeutic Equivalents

Do Physical properties contribute to drug activity.

What is drug receptor , How a drug resistance occurs

Mechanism of drug resistance

What is drug interaction

Drug interaction, and its examples

What is first pass metabolism of a drug

What is What is 510(k) Clearances ?

What is 510(k) Clearances,

Premarket Notification for medical devices – PMN or 510(k)

What is a drug interaction

Examples of drug interactions

Antibiotic Definition and classification

Antibiotic resitance and Antibiotic resistance mechanism

Antioxidants food suppliments

Vitamin D Details on FDA cautions on accurate dosage of Vitamin D

What is an antibody? what is monoclonal and polyclonal antibodies?

Terminologies In vaccine Production

Multi stage testing of Virus vaccine production

Testing of vaccines at different stages of production


Enzyme linked immunosorbent assay ELISA

Raido Immuno assay

Pharmaceutical Aseptic Manufacturing Process Terms , Terminology and Definitions.

Here are some articles which will be useful for you in further understanding of aspects of sterile dosage form manufacturing and regulatory affairs and good manufacturing practice in

pharmaceutical industry

Pharmaceutical Validation

Types of validations in pharmaceutical manufacturing

Requirements of documents for validation of sterilisation process

How to investigate OOS out of specification results

Determination of Phenol coefficient of a disinfectant

Sterility testing

Cleen Room Classification

Time limitations in sterile pharmaceuticals processing

Aspects of validation of manufacturing process in sterile pharmaceuticals

Clinical Trials

Controlling Pyrogens in injectable dosage forms

Media fill run process simulation aspects Validation of Aseptic Process and Sterilisation

New Drug Application (NDA) how to make a New Drug Application (NDA) to US FDA

Abbreviated New Drug Application (ANDA) What is ANDA , detaied information about ANDA preparation and submission to US FDA

How to make Investigational New Drug (IND) Application to US FDA

Drug applications submission to us fda Over the counter Drugs OTC drugs


Electronic record in pharmaceutical manufacturing industry

Good manufacturing practice in pharmaceutical industry

Pharmaceutical industry pharmaceutical companies and FDA latest updates

Here is an interesting article on world wide pharmaceutical industry and making a carrier in one of pharmaceutical companies article on Pharmaceutical Industry pharmaceutical industry

Find a Job in Pharmaceutical Company
To Find Pharmaceutical jobs and make a Pharmaceutical careers see here pharmaceutical companies
Here are some interesting articles on Quality assurance systems for pharmaceutical company

1.Quality assurance in pharma industry

2.Quality by designe concept for pharmaceutical industry

3.Quality by designe concept in pharmaceutical industryan explanation

%d bloggers like this: