Dissolution testing

Dissolution testing

In the pharmaceutical industry, drug dissolution testing is routinely used to provide critical in vitro drug release information for both quality control purposes, i.e., to assess batch-to-batch consistency of solid oral dosage forms such as tablets, and drug development, i.e., to predict in vivo drug release profiles.[1]

In vitro drug dissolution data generated from dissolution testing experiments can be related to in vivo pharmacokinetic data by means of in vitro-in vivo correlations (IVIVC). A well established predictive IVIVC model can be very helpful for drug formulation design and post-approval manufacturing changes.[2]

The main objective of developing and evaluating an IVIVC is to establish the dissolution test as a surrogate for human bioequivalence studies, as stated by the Food and Drug Administration (FDA). Analytical data from drug dissolution testing are sufficient in many cases to establish safety and efficacy of a drug product without in vivo tests, following minor formulation and manufacturing changes (Qureshi and Shabnam, 2001). Thus, the dissolution testing which is conducted in dissolution apparatus must be able to provide accurate and reproducible results.

Several dissolution apparatuses exist. In United States Pharmacopeia (USP) General Chapter <711> Dissolution, there are four dissolution apparatuses standardized and specified.[3] They are:

• USP Dissolution Apparatus 1 - Basket (37°C)

• USP Dissolution Apparatus 2 - Paddle (37°C)

• USP Dissolution Apparatus 3 - Reciprocating Cylinder (37°C)

• USP Dissolution Apparatus 4 - Flow-Through Cell (37°C)

USP Dissolution Apparatus 2 is the most widely used apparatus among these four.

The performances of dissolution apparatuses are highly dependent on hydrodynamics due to the nature of dissolution testing. The designs of the dissolution apparatuses and the ways of operating dissolution apparatuses have huge impacts on the hydrodynamics, thus the performances. Hydrodynamic studies in dissolution apparatuses were carried out by researchers over the past few years with both experimental methods and numerical modeling such as Computational Fluid Dynamics (CFD). The main target was USP Dissolution Apparatus 2.[1][4][5][6][7][8][9][10] The reason is that many researchers suspect that USP Dissolution Apparatus 2 provides inconsistent and sometimes faulty data.[11][12][13][14][15][16][17] The hydrodynamic studies of USP Dissolution Apparatus 2 mentioned above clearly showed that it does have intrinsic hydrodynamic issues which could result in problems. In 2005, Professor Piero Armenante from New Jersey Institute of Technology (NJIT) and Professor Fernando Muzzio from Rutgers University submitted a technical report to the FDA.[18] In this technical report, the intrinsic hydrodynamic issues with USP Dissolution Apparatus 2 based on the research findings of Armenante's group and Muzzio's group were discussed.

More recently, hydrodynamic studies were conducted in USP Dissolution Apparatus 4.[19][20][21]


  1. ^ a b Bai, G., Wang, Y., Armenante, P. M., “Velocity profiles and shear strain rate variability in the USP Dissolution Testing Apparatus 2 at Different Impeller Agitation Speeds, ” International Journal of Pharmaceutics, 403 (1-2), Pages 1-14, 2011
  2. ^ Kortejärvi H, Malkki J, Marvola M, Urtti A, Yliperttula M, Pajunen P., "Level A In Vitro-In Vivo Correlation (IVIVC) Model with Bayesian Approach to Formulation Series". J Pharm Sci. 95 (7), Pages 1595-1605, 2006.
  3. ^ United States Pharmacopeia 34/National Formulary 29, 2011.
  4. ^ Bai, G., Armenante, P. M., “Hydrodynamics, Mass transfer and Dissolution Effects Induced by Tablet Location during Dissolution Testing,” Journal of Pharmaceutical Sciences, Volume 98, Issue 4, Pages 1511-1531, 2009
  5. ^ Bai, G., Armenante, P. M., “ Velocity Distribution and Shear Rate Variability Resulting from Changes in the Impeller Location in the USP Dissolution Testing Apparatus II, “ Pharmaceutical Research, Volume 25, Issue 2, Pages 320-336, 2008
  6. ^ Bai, G., Armenante, P. M., Plank, R. V., “Experimental and Computational Determination of Blend Time in USP Dissolution Testing Apparatus II,” Journal of Pharmaceutical Sciences, Volume 96, Issue 11, Pages 3072-3086, 2007.
  7. ^ Bai, G., Armenante, P. M., Plank, R. V., Gentzler, M., Ford, K. and Harmon P., “Hydrodynamic Investigation of USP Dissolution Test Apparatus II,” Journal of Pharmaceutical Sciences, Volume 96, Issue 9, Pages 2327-2349, 2007.
  8. ^ Kukura J., Baxter JL., Muzzio FJ., "Shear distribution and variability in the USP Apparatus 2 under turbulent conditions". Int J Pharm. 279 (1-2), Pages 9–17, 2004.
  9. ^ Baxter JL, Kukura J, Muzzio FJ. "Hydrodynamics-induced variability in the USP Apparatus II Dissolution Test". Int J Pharmaceutics 292 (1-2), Pages 17–28, 2005
  10. ^ McCarthy L., Bradley G., Sexton J., Corrigan O., Healy AM., "Computational fluid dynamics modeling of the paddle dissolution apparatus: Agitation rate mixing patterns and fluid velocities". AAPS Pharm Sci Tech 5 (2), 2004.
  11. ^ Cox DC., Furman WB., Thornton LK., 1983. Systematic error associated with Apparatus 2 of the USP Dissolution Test III: Limitation of Calibrators and the USP Suitability Test. J Pharm Sci. 72 (8), 910– 913.
  12. ^ Cox DC., Furman WB., 1982. Systematic error associated with Apparatus 2 of the USP dissolution test I: Effects of physical alignment of the dissolution apparatus. J Pharm Sci 71 (4), 451–452.
  13. ^ Moore TW., Hamilton JF., Kerner CM., 1995. Dissolution testing: Limitation of USP prednisone and salicylic acid calibrator tablets. Pharmacopeial Forum 21 (5), 1387–1396.
  14. ^ Costa P, Lobo JMS . 2001 . Influence of dissolution medium agitation on release profiles of sustainedrelease tablets. Drug Devel Ind Pharm 27 (8), 811–817.
  15. ^ Qureshi SA., McGilveray IJ., 1999. Typical variability in drug dissolution testing: study with USP and FDA calibrator tablets ad a marketed drug (glibenclamide) product. Eur J Pharm Sci. 7 (3), 249-258
  16. ^ Qureshi SA., Shabnam J., 2001. Cause of high variability in drug dissolution testing and its impact on setting tolerances. Euro J Pharm Sci. 12 (3),271–276.
  17. ^ Mauger J., Ballard J., Brockson R., De S., Gray V., Robinson D., 2003. Intrinsic dissolution performance of the USP dissolution apparatus 2 (rotating paddle) using modified salicylic acid calibration tablets: Proof of principle. Dissol Technol 10(3), 6–15.
  18. ^ [1]
  19. ^ Kakhi, M.,"Mathematical modeling of the fluid dynamics in the flow-through cell",International Journal of Pharmaceutics, 376 (1-2), pp. 22-40, 2009
  20. ^ Kakhi, M.,"Classification of the flow regimes in the flow-through cell", European Journal of Pharmaceutical Sciences, 37 (5), pp. 531-544, 2009
  21. ^ D'Arcy, D.M., Liu, B., Bradley, G., Healy, A.M., Corrigan, O.I.,"Hydrodynamic and species transfer simulations in the USP 4 dissolution apparatus: Considerations for dissolution in a low velocity pulsing flow", Pharmaceutical Research 27 (2), pp. 246-258, 2010

Wikimedia Foundation. 2010.

Look at other dictionaries:

  • Dissolution (chemistry) — Making a saline water solution by dissolving table salt (NaCl) in water. The salt is the solute and the water the solvent …   Wikipedia

  • Simulations Plus — Infobox Company name = Simulations Plus, Inc. type = Public (NASDAQ|SLP) foundation = 1996 in Lancaster, California founder = Walter Woltosz location city = Lancaster, California location country = USA industry = Software num employees = 20… …   Wikipedia

  • Varian, Inc. — For other uses of Varian , see Varian (disambiguation). Varian Inc. Type Public (NASDAQ: VARI) Industry Scientific instruments Fate Acquired by Agilent Technologies …   Wikipedia

  • Prednisone — For the active metabolite of prednisone which is also used as a drug including as eye drops, see prednisolone. Prednisone Systematic (I …   Wikipedia

  • Laboratory Robotics Interest Group — The Laboratory Robotics Interest Group (LRIG) [http://lab robotics.org/] is an international non profit organization dedicated to the study and discussion of laboratory automation. Through mailing lists, forums, and online presentations, as well… …   Wikipedia

  • Polyanhydrides — are a class of biodegradable polymers characterized by anhydride bonds that connect monomer units of the polymer chain. Their main application is in the medical device and pharmaceutical industry. In vivo, polyanhydrides degrade into non toxic… …   Wikipedia

  • List of Statutory Instruments of the United Kingdom, 1993 — This is a complete list of all 1844 Statutory Instruments published in the United Kingdom in the year 1993. NOTOC 1 100* Environmental Protection (Controls on Injurious Substances) Regulations 1993 S.I. 1993/1 * Rail Crossing Extinguishment and… …   Wikipedia

  • international relations — a branch of political science dealing with the relations between nations. [1970 75] * * * Study of the relations of states with each other and with international organizations and certain subnational entities (e.g., bureaucracies and political… …   Universalium

  • List of Statutory Instruments of the United Kingdom, 1989 — NOTOC This is a complete list of all 1534 Statutory Instruments published in the United Kingdom in the year 1989.1 100* Criminal Justice Act 1988 (Commencement No. 5) Order 1989 S.I. 1989/1 * Food Protection (Emergency Prohibitions) (Wales)… …   Wikipedia

  • List of Statutory Instruments of the United Kingdom, 2007 — This is an incomplete list of Statutory Instruments of the United Kingdom in 2007. NOTOC 1 100* Cider and Perry and Wine and Made wine (Amendment) Regulations 2007 S.I. 2007/4 * Customs and Excise (Personal Reliefs for Special Visitors)… …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”