One aim of dissolution testing is to guarantee the quality of the pharmaceutical product, in order to prove consstency from one batch to another and that no important change occurs during the stability study, change that could impact the efficacy of the pharmaceutical product.

In order to detect unconsistencies and changes, the retained conditions (basket or paddle for tablets, medium type, rotation speed, volume, pH, sampling times, use of sinker or not, etc.) should be discriminant. That means that the dissolution test should highlight a change when it occurs. The best way to prove discriminance is to have "bad batches", and the different (pre-) pilot batches may help to prove this discriminance. A dissolution test that goes too fast (100% dissolved within 5 or 10 minutes) will certainly mask potential differences between a "bad" batch and a "good" batch.

I agree with john micheal. USP apparatus 2 is the commonly used. To adjust rpm and volume you should do preliminary tests in order to know the cinetic of your tablet drug release.

As per our industry concern we will first prefer to go to the pharmacopoeial method but if the results are not good or the desired result not achieved we will develop a new method will complete validation and do not deviating any type of clause of regulatory requirement

USP apparatus 2 is the commonly used but it depend upon the type of tablet.

Selection of a dissolution apparatus, the way you perform in industries depend on many factors - -

1) Country in which the industry wants to launch the product?

If its USA, it should meet USP; japan ---- JP; india --- IP etc..... If you want to sell in a country, prove that your product meets their pharmacopoeial limits

2) Whether an established method for dissolution testing of Drug or its product is available in pharmacopoeia or not?

If yes, go on as per their procedure

If no, go for any other good pharmacopoeial test already set for a particular product.

else You can go for your own inhouse methods...

Also there will be some other factors ---

why certain industries do inhouse tests specifically, However they show that their product meets the limits

Agreed with most of the answer above, iys all depand on the type of formulation but must conform with official pharmacopea,!

Purpose of dissolution test is to demonstrate drug availabilty in the body for the desired serum level. If any product qualifies for the dissolution test it will never fail for Bioavailability.

Methods given in pharmacopeias are very clearly defined for all testing conditions based on the data derived at the time of drug design.

If any product is in any Pharmacopeia it is expected and mandatory to use same set of parameters defined in the Monograph. If it is not part of Pharmacopeia, one shall define its own set of parameters based on scientific work carried out to justify the Formulation design. ICH guidelines for CTD can be a good starting point to define own parameters for non-Pharmacopieal products.

Bottom line is ,for Pharmacopieal products follow Monograph and for non Pharmacopieal products prove that your driven method is robust enough to discriminate the bad product from Good.

Here is the link to FDA Dissolution Methods (Printable List of All Drugs in the Database).

http://www.accessdata.fda.gov/scripts/cder/dissolution/dsp_SearchResults_Dissolutions.cfm?PrintAll=1

In India we must follow the I.P. methods

maybe the ICH guideline Q4B annex 7 (R2) on dissolution test –

general chapter

could be helpful for you (interchangeability of dissolution tests in the different ICH regions):

http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500044301.pdf

and there is a new draft version of the European Guideline on quality of oral modified release products available (with a chapter on dissolution):

http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/09/WC500132403.pdf

the bioequivalence guideline states regarding dissolution testing:

Test methods should be developed product related based on general and/or specific pharmacopoeial requirements. In case those requirements are shown to be unsatisfactory and/or do not reflect the in vivo dissolution (i.e. biorelevance) alternative methods can be considered when justified that these are discriminatory and able to differentiate between batches with acceptable and non-acceptable performance of the product in vivo. Current state-of-the-art information including the interplay of characteristics derived from the BCS classification and the dosage form must always be considered.

http://www.emea.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf

The official dissolution tests in the pharmacopoeias are sufficient for most tablets. However, manufacturers can develop their own in-house dissolution test provided that such tests can be validated and the results obtained are comparable with the official methods.

The official dissolution tests in the pharmacopoeias are mostly used for all types of tablets , few industries have their own in- house methods, I have personal experience of using Paddle method in the laboratory as well as in the industry, and I got good/accurate results

The most suitable method will depend on the type of tablet dosage form, whether it is intended for immediate release, sustained release, colon targeting or otherwise of floating type. In fact the compendial monograph provides sufficient details about the use of a suitable method. In case you are formulating a modified release tablet of an already approved drug moiety then SUPAC-MR guidelines from FDA or the BA/BE guidelines given by Central Drug Standard Control Organization will help you to select the right dissolution medium and method applicable.

For compendial products, there are specific guidelines both for apparatus and dissolution medium at the FDA website. However, non-compendial or New Molecule entity (NME), you may have to search for the innovator method (it is difficult to find) or you may have to develop your own in-house method based on experience of the physico-chemical properties of similar molecules in the market.

As had been variously stated, choice of dissolution method must be based on country of manufacture and/or distribution of the finished solid dosage form (mostly capsules and tablets). USP, BP, EP and JP are the most frequently referenced. For immediate release tablets and capsules, USP/BP apparatus I or II are the usual methods. Paddle Apparatus (Apparatus II) is also specified for a number of sustained released products in the USP with additional requirements for biorelevant dissolution fluids (i.e. simulated gastric and intestinal fluid). Generally, the main differences between Apparatuses I and II is the placement of the dosage unit and the speed of rotation: Apparatus I is generally rotated @ 100 rpm and the dosage unit is placed in a "basket" assembly which is suspended in the medium while Apparatus II is usually rotated @ 50 rpm and the unit is simply dropped in the dissolution medium and settles to the bottom of the vessel

For products designed from new chemical entities (i.e. products not yet in an official monograph), ICH guidelines and QbD initiatives of US FDA have guidelines for ensuring extendability of laboratory scale dissolution data to pilot and commercial batches by combining risk assessment of product failure and robustness of experimental data in design space definition. These require thorough understanding of raw materials characteristics and comprehensive definition of finished product attributes. The ultimate product quality is bioavailability (i.e. the quality parameter that predicts in vivo performance). Hence, unless the drug substance in the tablet/capsule belongs to the BCS Class 1, it is very likely that in vitro-in vivo correlation data will be required before the product of a new chemical entity can be registered. So, there is no one best method: a number of factors will need to be considered before arriving at a method of choice.

In instances where a compendial (e.g. USP, Ph Eur, Ph Jap) methods is employed for in vitro drug release testing, the experimental test conditions, qualifications and validations steps should conform to those discussed in the FIP and FDA Guidelines on dissolution testing

As a general answer, I'd say that there is no possibility to generalize, unless the aim and the context are known.

As a general consideration we should answer before this question: do we want to devise a test for a drug substance of interest (intrinsic solubility or dissolution, BCS classification, .. ), or, in case of a drug product, do we want to develop a dissolution test for formulation development of a new dosage form (generic application or not), or do we want to develop a dissolution test suitable for QC purpose, or do we want to devise a test that is suitable for both purposes,... ????

Even more do we want to develop a dissolution test that may serve as a surrogate for bioavailability/bioequivalence studies?

As you see these aims need different approaches, Compendial tests are essential but in themselsed they do not give direct answers to thewe questions. The answer has to be find by combining a deep knowledge of all the relevant compendial chapters and quality/efficacy guidelines.

Please remember the scholar message that dissolution test has both a physical and a biopharmaceutical meaning.

I think the best method for dissolution testing of tablet is by using paddle type of dissolution testing apparatus.

They do have their in-house protocols

First try using USP Apparatus II (paddles), 50 rpm, acid conditions, 900 mL, 37 +/- 0.5 ºC; for more discriminating conditions or special conditions you will need to make suitable changes.

The most suitable method will depend on the type of tablet dosage form, whether it is intended for immediate release, sustained release, colon targeting or otherwise of floating type. In fact the official monographs provides sufficient details about the use of a suitable method. No any Indistry can deviate from the official method but yes they can use their own protocols.

The following links may be useful in this regard:

Selecting a Dissolution Apparatus – Some Practical Considerations (http://www.drug-dissolution-testing.com/?p=1524).

Dissolution method development: Perhaps the most wasteful of all the current practices! (http://www.drug-dissolution-testing.com/?p=1906)

Worth repeating it: Drug and/or product dependent dissolution tests are scientifically invalid. They do not provide dissolution characteristics of products even for QC purposes. (http://www.drug-dissolution-testing.com/?p=1886)

Drug dissolution testing: Limitations of current practices and requirements (http://www.drug-dissolution-testing.com/?p=1792).

The science of drug dissolution testing: Testers or apparatuses, experimental conditions and interpretation of results – A systematic approach for learning (http://www.drug-dissolution-testing.com/?p=1668).

Initially you need to check if the product appears in the Pharmacopoeia or not. If so you should adjust your formulation parameters that gives monograph. If notappears in the pharmacopeia, you assign the parameters, taking into account the pharmacological activity, pharmacokinetic and pharmacodynamic characteristics. Importantly you get to compare your product against the product innovator or leader.

American Pharmaceutical Review covered this topic a few months back.

Try this: http://www.americanpharmaceuticalreview.com/1430-SearchResults/?search=dissolution

Best dissolution method (what ever whether it is USP or in house method) should be able to correlate with In vivo Bioavailability testing. Based on in vivo bioavailability kinetics, the in vitro method should be designed.

If possible, please consider attending the upcoming evening seminar on the topic. I plan to address this very question in the seminar. Please follow the link for details (http://www.drug-dissolution-testing.com/?p=2017)

Looking forward to seeing you in Toronto.

With kind regards.

There are no definite rules for selecting a dissolution method for a definite drug. In fact, the dissolution method is selected according to IVIVC results to simulate in vivo absorption kinetics. Therefore, it is up to the one who develops the product to set up the dissolution method. However, to qualify the methods which may differ significantly from different researchers for reasons of easy manipulation by quality control units, the dissolution methods should be restrained to what can be generally accepted. So, this is why we need a Pharmacopeioa.

The answer is to use freely the procedures that fits your product within the limits of local Pharmacopeoia.

The following links/articles would be useful in response to the post above:

(1) Confusion about IVIVC and predicting plasma drug levels (http://www.drug-dissolution-testing.com/?p=2013).

(2) Developing an IVIVC: Time Spent = Time Wasted (http://www.drug-dissolution-testing.com/?p=1643).

(3) Why are current practices of dissolution testing so confusing, frustrating and complex? Because they are not based on scientific principles but on rituals! (http://www.drug-dissolution-testing.com/?p=1945).

(4) Costly mistake formulators/analysts often make i.e. developing a product dependent dissolution test (http://www.drug-dissolution-testing.com/?p=1696).

(5) Developing Dissolution Methods for Pharmacopeial Purposes – Deficiencies (http://www.drug-dissolution-testing.com/?p=1451).

Dear Raj:

I personally do not have experience with conducting or using dialysis set up. So, my response is of general nature.

A dissolution test is conducted to evaluate releasing of drug from a product (mostly tablets and capsules) and its dissolution under the physiological environment (37C, water or buffer, stirring/mixing). I do not think dialysis set would be able to fulfill these requirements thus should not be used for dissolution testing.

On the other hand, dialysis may be more suited to drug penetration studies, which is a drug characteristic, however, dissolution tests are conducted for PRODUCTS.

I hope this is helpful.

Regards

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