Question and Answer Section

William Brown and Margareth Marques
The following questions have been submitted by readers of Dissolution Technologies. Margareth Marques, Ph.D. and Will Brown, United States Phamacopeia, authored responses to each of the questions.
*Note: These are opinions and interpretations of the authors, and are not necessarily the official viewpoints of the USP

Email for correspondence: web@usp.org

Q What grade of water is used to prepare dissolution media?
A It is recommended to use Purified water (USP monograph) in the preparation of dissolution media. See the Reagents, Indicators, and Solutions section of USP 28, page 2791.

Q Is peanut oil used in the preparation of dissolution media?
A The effect of food on the release mechanism of pharmaceutical dosage forms can be evaluated in vitro using dissolution media that can simulate the in vivo conditions. This type of media can be prepared with a pH range from 1.2 to 7.8 to mimic the gastrointestinal tract. Enzymes and bile salts can be added to this media to mimic foodinduced changes in the different parts of the GI tract. Also, the addition of oil to the media can simulate the fatty component of a meal. Several vegetable oils, including peanut oil, can be used for this purpose. See El–arini, S. K., Shiu, G. K., Skelly, J. P. – Theophylline–controlled release preparations and fatty food:An in vitro study using the rotating dialysis cell method. Pharm.Res., 7(11):1134 – 1140, 1990.

Q Which are the possible compositions of dissolution media?
A The list of possible dissolution media is very long.You can find several different dissolution media in the USP monographs, in the new general chapter <1092> The Dissolution Procedure:Development and Validation, published in Pharmacopeial Forum 31(5): 1463 – 1475, 2005. Also, you can find suggestions of dissolution media in papers published in Dissol.Technol. and at www.NCBI.NLM.NIH.GOV (access free of charge).

Q When evaluating the dissolution of pharmaceutical dosage forms containing poorly soluble drugs, if the addition of surfactants or a hydroalcoholic medium is not appropriate, can buffers of high pH, i.e.above pH 8.0, be used?
A The selection of the media composition for dissolution testing is based on the need for discriminatory power and ruggedness of the test, on the stability of the analyte in the test medium, and on the relevance to in vivo performance. Oral formulations should be evaluated in the physiologic pH range of 1.2 to 6.8 (1.2 to 7.5 for modified–release formulations). The use of a dissolution medium with pH outside of these ranges should be justified. The use of organic solvents is discouraged. Surfactants may be used to enhance drug solubility. The type of surfactant and the concentration employed should be justified by dissolution profiles in the different conditions. Sodium lauryl sulfate is not always the best option, the surfactant should be compatible with the drug substance and with the composition of the medium, and this is not always the case for this particular surfactant. Possible surfactants used in dissolution testing are:

) You can find useful information on the selection of the type and concentration of surfactants in dissolution medium in these two papers: 1 – Noory, C., Tran, N., Ouderkirk, L., and Shah, V. – Steps for development of a dissolution test for sparingly water–soluble drug products. Dissol.Technol. 7(1): 16 – 18, 2000. 2 – Brown, C. K., Chokshi, H. P., Nickerson, B., Reed, R. A., Rohrs, B. R., Shah, P. A. – Acceptable analytical practices for dissolution testing of poorly soluble compounds. Pharm.Tech., Dec 2004, 56 – 65.

Q Q During the stability studies of an extendedrelease tablet what basis should be used in the calculation of amount of drug released; the assay result obtained at the time point of the evaluation or the label content?
A All results in the evaluation of dissolution testing are calculated based on the label claim of the product or on the dose released (this is case of transdermal patches and osmotic pump tablets) and not on the actual assay result.

Q For the evaluation of drug release of a product in a suspension for injection (depot), the USP apparatus 4 seems to be the instrument of choice.Which are the cells that could be used with this apparatus?
A The drug release of suspensions for injection (depot), liposomes, nanospheres, microspheres, etc., can be evaluated using USP Apparatus 4 with the 12 mm or 22.6 mm tablet cell depending on the sample size. Often the suspension is placed in the middle of the glass bead bed that may fill the cell. The manufacturers of this apparatus can customize the cells according to the characteristics of your product. Figure 1 shows some of the cells that can be used with USP Apparatus 4.