Dissolution and Dissolution Apparatus: A Review

2020

In the pharmaceutical industry, dissolution study is one of the vital tests for the evaluation of the pharmaceutical dosage form. Dissolution test is the most important tool for the testing of drug release profile of solid dosage form in the pharmaceutical preparation. Dissolution studies provide the knowledge about the efficacy of the dosage form. Dissolution tests are major for performing a various kind of investigations like drug degradation profiles, stability and shelf life studies, chemical stability and so on. Dissolution test can be easily performed in both the small and large scale with the proper techniques and it is also used for the comparison between the graph profile of the similar and different dosage form. Hence, it can be considered as the most qualitative and convenient test for the evaluation of the pharmaceutical solid dosage form.

Dissolution test is required to study the drug release from the dosage form and its in vivo performance. Dissolution test is used to asses the lot to lot quality of drug product. The development and validation of dissolution procedures is of paramount importance during development of new formulation and in quality control. The dissolution procedure must be properly developed and validated. The objective of this paper is to review the development and validation of dissolution procedure(s) and to provide practical approaches for determining specificity, linearity, range, accuracy, precision, limit of detection, limit of quantitation and robustness of methods. Developing and validating dissolution test procedures can be a challenging process, on multiple fronts. Methods must be developed and validated not just for the dissolution test procedure itself, but also for any assay used to evaluate the test results. INTRODUCTION The dissolution test is required for various dosage forms for product release testing. It is also commonly used as a predictor of the in vivo performance of a drug product. To satisfy dissolution requirements, the USP provides information in the way of a general chapter on dissolution, as well as related chapters on disintegration and drug release (USP 32-NF 27, 2009). The USP and FDA also provide guidelines on development and validation of dissolution procedures (USP 32-NF 27, 2009; ICH guideline, 2005; Guidance for Industry 1997, 2000) and while this white paper will draw from this information and will discuss the available guidance in some detail, the reader is encouraged to consult the reference for additional details. In vitro dissolution data, together with bioavaibility and chemistry, manufacturing and control data, is a critical component of any new drug application (NDA) submitted to the FDA. A dissolution test is really a simple concept; a tablet or capsule is placed into a known volume of media and as it dissolves the resulting solution is sampled over time, and assayed (often by HPLC or by spectrophotometry) for the level of active pharmaceutical ingredient (API) present. However, the design, development, and the validation of the procedure can be quite involved, especially when one considers that not only the dissolution procedure must be developed and validated, but also any analytical technique used for the assay.

2006

Dissolution Technologies

In vitro dissolution testing can serve as an effective and efficient tool for evaluating the influence of formulation and manufacturing variables on drug release characteristics. The targeted purpose will determine the method used and the implications of the test results. Regardless of its intended purpose, it is necessary to understand the factors influencing in vitro dissolution outcomes to avoid the introduction of error into the data interpretation. This will influence the selection of the in vitro test procedure, ensuring that the method can identify changes in the critical formulation and manufacturing variables. There is also a need to understand the rate limiting factors influencing in vivo product bioavailability both from a dissolution and an absorption perspective. Finally, to achieve in vivo biorelevance, it is necessary to understand how the selected in vitro dissolution test method reflects the variables impacting in vivo product dissolution behavior. This primer summarizes and integrates these diverse variables, fostering an appreciation of the strengths and potential pitfalls that may be encountered during the generation and analysis of in vitro dissolution profiles associated with oral dosage forms. This understanding is needed for developing a well-designed dissolution test procedure that is appropriately fit for purpose.

2010

Standard compendia dissolution apparatus are the first choice for development of new dissolution methods. Nevertheless, limitations coming from the amount of material available, analytical sensitivity, lack of discrimination or biorelevance may warrant the use of non compendial methods. In this regard, the use of small volume dissolution methods offers strong advantages. The present study aims primarily to evaluate the dissolution performance of various drug products having different release mechanisms, using commercially available small volume USP2 dissolution equipment. The present series of tests indicate that the small volume dissolution is a useful tool for the characterization of immediate release drug product. Depending on the release mechanism, different speed factors are proposed to mimic common one liter vessel performance. In addition, by increasing the discriminating power of the dissolution method, it potentially improves know how about formulations and on typical events which are evaluated during pharmaceutical development such as ageing or scale-up. In this regard, small volume dissolution is a method of choice in case of screening for critical quality attributes of rapidly dissolving tablets, where it is often difficult to detect differences using standard working conditions.

Dissolution Technologies

Intrinsic dissolution testing has been applied for characterization of pure API with respect to its dissolution behavior. The effect of formulation factors and processing parameters on dissolution rate is evaluated by dissolution testing of the final product, which is a time and resource-consuming process. Our objective was to use intrinsic dissolution testing for determining the effect of processing parameters on drug release. In the present study, an intrinsic dissolution testing method was developed for atenolol and validated according to the standard guidelines using USP-recommended dissolution media. Various experimental variables (compaction pressure and rotation speed of the disk) were optimized by studying at three levels. Atenolol was subjected to granulation in a super mixer granulator by applying standard wet granulation protocols. Granulation time and binder concentration were taken as process variables while dissolution rate was a response variable. Dissolution media had no interference with sample analysis, and all validation parameters for the developed method were in an acceptable range (%RSD > 1). The intrinsic dissolution rate of atenolol (1.84 ± 0.13 mg/cm 2 min) was high due to its better solubility in dissolution media. The dissolution rate of atenolol was decreased by granulating with PVP under different conditions. We concluded that intrinsic dissolution testing method can be applied for determining the effect of processing parameters on dissolution rate of the API at the pre-compression level. This method will reduce experimentation for optimization of dissolution rate and will spare time and resources.

Pharmaceutics, 2010

Standard compendia dissolution apparatus are the first choice for development of new dissolution methods. Nevertheless, limitations coming from the amount of material available, analytical sensitivity, lack of discrimination or biorelevance may warrant the use of non compendial methods. In this regard, the use of small volume dissolution methods offers strong advantages. The present study aims primarily to evaluate the dissolution performance of various drug products having different release mechanisms, using commercially available small volume USP2 dissolution equipment. The present series of tests indicate that the small volume dissolution is a useful tool for the characterization of immediate release drug product. Depending on the release mechanism, different speed factors are proposed to mimic common one liter vessel performance. In addition, by increasing the discriminating power of the dissolution method, it potentially improves know how about formulations and on typical events which are evaluated during pharmaceutical development such as ageing or scale-up. In this regard, small volume dissolution is a method of choice in case of screening for critical quality attributes of rapidly dissolving tablets, where it is often difficult to detect differences using standard working conditions.

International Standard Book Number-10: 0-8247-5467-0 (Hardcover) International Standard Book This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use.