A Compliance Perspective on Dissolution Method Validation for Immediate-Release Solid Oral Dosage Forms on Automated Instrumentation - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

  • Search
  • Suppliers
  • Careers

Enter a company or product name

KeywordLocation
About Search
A Compliance Perspective on Dissolution Method Validation for Immediate-Release Solid Oral Dosage Forms on Automated Instrumentation
An automated dissolution method can be a powerful tool to test drug products at all phases of their development. With minimal automated method validation, this tool can be used early in the drug-evaluation process. And with additional validation efforts, an automated method can be extended to the testing of Phase IV stability batches. Validating an automated dissolution-test method requires an understanding of the potential effects from filtration parameters, system interference, carry-over, cleaning..
Sep 2, 2006
By: David Fortunato
Pharmaceutical Technology

12345
Next »

As the pace of product development accelerates, the approach to dissolution-method development must advance beyond a manual method and an assay. A natural progression of the method-development process must include the transfer of the manual method onto automated instrumentation.

Validating the automated method is the primary challenge when transferring from the manual method. A dissolution scientist must understand the potential effects from filtration, system interference, carry-over, cleaning parameters, and media replacement. Automated dissolution instrumentation can help generate good manufacturing practice (GMP) data only when validated testing parameters can negate these influences, so the dissolution scientist can be confident that results do not differ between the manual and the automated methods. In addition, all laboratory equipment used to support or generate GMP data about automated instrumentation must follow an instrument "chain of compliance." Proper documentation must exist that proves each piece of equipment has been properly qualified and calibrated for its intended use.

Product development life cycle


Tips for validating automated dissolution parameters
The level of automated dissolution-method validation depends upon a product's phase of development. For early-phase products, minimal validation is required to screen the initial batches. Typically, filtration parameters must be established first to ensure that no amount of active pharmaceutical ingredient (API) is lost with filtration. The initial filtration parameters could be established manually and then transferred to the automated instrument. Next, automated dissolution-profile testing is completed to screen several different dissolution media. Profile sampling could be performed at 10, 20, 30, 45, and 60 min and the results compared. Selecting the various dissolution media that are used in the evaluation depends upon the solubility and stability of the API in each media. This process allows a dissolution chemist to determine quickly the media having the potential to provide the most discriminating dissolution performance for the product. Once these initial parameters have been established, a dissolution chemist can use the automated instrumentation to quickly screen early formulations and help formulators direct their future formulation efforts.

As the life cycle of the product progresses, automated dissolution-method parameters must be validated if the generated data have the potential to be included in any type of GMP submission. At this phase of development, a dissolution chemist should have substantial experience performing both manual and automated dissolutions on a product. This experience can be useful to select automated dissolution method parameters, which should be able to generate results equivalent to those of manual dissolution tests.


Ensuring instrument qualification
Because the manual test is considered the "official" dissolution test, side-by-side dissolution-profile testing should be conducted manually and with automation. Results could be compared at 10, 20, 30, 45, 60, and infinity minutes. At the infinity time point, a final sample is taken after the dissolution has progressed with a stirring apparatus speed of 250 rpm for an additional 30 min after the Q time point. The chosen acceptance criteria for the comparison between the two methods should reflect and compensate for both nonvariable and highly variable drug products. The results generated at the earlier time points are the most significant because they have the highest potential for variation between the manual and automated methods. If comparable results are obtained between the two methods at the earlier time points, a dissolution chemist is more likely to be assured that accurate data are obtained at all time points of the automated dissolution-profile testing. At later time points, the percent drug released typically approaches 100%; therefore, not as much variation between the two tests would be expected at these later time points. Acceptance criteria must be established for results generated at the earlier time points (<85% dissolved) and the later time points (>85% dissolved) with tighter acceptance criteria established at the later time points.

12345
Next »

ADVERTISEMENT

RELATED CONTENT
The Effect of Core and Coating Composition on Drug Release from Directly Compressed Time-Controlled Release Tablets
The Impact of Impurity Analysis on Future Regulations
Implementation of Water-Activity Testing to Replace Karl Fischer Water Testing for Solid Oral-Dosage Forms
US Court Delays FDA Drug Pedigree Requirements
New X-ray Microscopy Method Sheds Light on Nanoscale Reactions
post a comment
Please complete the form below to post your comment.
Bold = Required
Email Address Your email address will NOT be published.
Display Name appears with your comment
City
State
Country
Remember me: YesNo
Comment read our privacy policy
Note: does not support HTML
All comments submitted are subject to review, and may be delayed before posting. We reserve the right not to post comments.
About the Author

David Fortunato


David Fortunato is a scientist in the Chem Pharm division of Analytical Development, US, Johnson and Johnson Pharmaceutical Research and Development, LLC. Articles by David Fortunato
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
What factor do you think will be most significant in 2010 for determining the health of the market for contract manufacturing of active pharmaceutical ingredients?
The global economic recovery
The US economic recovery
Improved credit and financing flow to the small to emerging pharma/bio sector
Less restrictive inventory control by pharmaceutical companies
The level of competition from contract manufacturers in emerging markets
The global economic recovery
40%
The US economic recovery
14%
Improved credit and financing flow to the small to emerging pharma/bio sector
14%
Less restrictive inventory control by pharmaceutical companies
9%
The level of competition from contract manufacturers in emerging markets
24%
View Results
Eric LangerOutsourcing OutlookEric Langer A Bio View of Outsourcing
Patricia Van ArnumIngredients InsiderPatricia Van Arnum Advances in Custom Synthesis
Faiz kermaniSpotlightFaiz Kermani EU pricing dilemmas
Faiz kermaniStatistical Solutions Lynn Torbeck%RSD: Friend or Foe?
Keep an eye on that cargo
Pharma packs a punch
Another Boost for Vaccines
Rodney Dangerfield and R&D
Federal Spending Freeze Could Threaten Supply-Chain Security

FindPharma Custom Search
Featured Jobs

More Jobs

Source: Pharmaceutical Technology, 9/2/2006
Click here