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

Figure 1

Q What is a Palmieri basket?
A It is a basket developed by A. Palmieri (see Drug Development in Industrial Pharmacy,7:246–259,1981) used to evaluate the release of drugs from suppository bases. It adapts to the drive of the standard USP Apparatus 1 (basket). See Figure 1.

Q What is the difference between multiple time points and dissolution profile?
A In a dissolution profile,the amount of drug release is quantified as a function of time.These measurements are made until a plateau is reached for the amount of drug released. In most cases,the time will be in minutes for immediate release dosage forms,and in hours for modified release dosage forms. It can even be days for dosage forms like transdermal patches.

To better evaluate the quality or performance of some products it will be useful to know the amount of drug release at particular time points or at multiple time points. For modified release dosage forms,this evaluation should be at least at three different time points:one at early stages to evaluate possible dose dumping,a second one at the middle of the dissolution profile,and a third one at the last stage of drug release profile.Additional points may be useful depending on the type of drug release mechanism employed.The use of multiple time points may be advantageous for certain immediate release products.One good example is carbamazepine tablets (see Dissolution Test 2 in the USP monograph on page 343 of USP 28).

Q What is the preferable quantitative method,HPLC or spectrophotometry,recommended to be used in the calibration of dissolution equipments using USP calibrator tablets?
A According to the technical information supplied with the USP calibrator tablets (available at www.usp.org/standards/ calibrators.html),the analysis is intended to be by UV.The collaborative study performed to determine the acceptance ranges for the USP calibrator tablets was done by UV analysis. A validated HPLC method may be used as an alternative method.

Q Is the calculation of difference factor (f₁) and similarity factor (f₂) applicable for comparing a tablet with a capsule?
A To use the independent model proposed by Moore and Flanner (see Pharm Tech.,20(6): 64 – 74,1996) to compare dissolution profiles using the two factors,f₁ and f₂,the dissolution measurements of the two products being compared should be made under the same test conditions.The medium,apparatus and time points should be the same for both products.This may be not possible when evaluating capsules and tablets.Also,you need to verify with your local regulatory authorities if they accept interchangeability between capsules and tablets.Most of the regulatory agencies consider tablets and capsules to be different pharmaceutical dosage forms and not interchangeable.

Q Are there any other approaches besides the calculation of difference factor (f₁) and similarity factor (f₂) to compare dissolution profiles?
A There are several different models in the literature that can be used to compare dissolution profiles. Some of them are:- Yuksel,N.,Kanik,A. E.,Baykara,T.�Comparison of in vitro dissolution profiles by ANOVA-based,model-dependent and –independent methods. Int.J.Pharmaceutics,209:57–67, 2000. – Saranadasa,H.�Defining similarity of dissolution profiles through Hotelling�s T² statistic. Pharm. Technol., February 2001,46–54. – Seo,P. R.,Shah,V. P.,Polli,J. E.�Novel metrics to compare dissolution profiles. Pharm.Dev.Technol., 7(2):257–265,2002. – Costa,P.,Lobo,J.M. S.�Modeling and comparison of dissolution profiles. Eur.J.Pharm.Sci.,13: 123–133,2001. – Adams,E. et all.�Evaluation of dissolution profiles using principal component analysis. Int.J.Pharmaceutics, 212:41–53,2001.

Q Do the weight differences between individual prednisone or salicylic acid calibrator tablets affect the dissolution results?
A The calibration using these tablets typically does not produce results representing 100 % dissolution. Salicylic Acid tablets are non-disintegrating and the dissolution rate is dependent on the surface area exposed. The disintegrating prednisone tablets dissolution rate depends on how fast the surface of the drug particles is exposed to the medium. It is our understanding that neither of these tablets will give different results based on the small differences that may be seen in either drug loading or tablet weight. As part of the initial evaluation of a new lot of calibrator tablets,the USP laboratory evaluates the assay value and the uniformity of individual tablets. Typically the variability in salicylic acid tablet mass is approximately 2% RSD. The variability of prednisone content in a recent lot of disintegrating calibrator tablets was also about 2 % RSD.