Dissolution test is widely used in the pharmaceutical industry for optimization of formulation and quality control of different dosage forms.
Dissolution is pharmaceutically defined as the rate of mass transfer from a solid surface into the dissolution medium or solvent under standardized conditions of liquid/solid interface, temperature and solvent composition. It is a dynamic property that changes with time and explains the process by which a homogenous mixture of a solid or a liquid can be obtained in a solvent. It happens to chemically occur by the crystal break down into individual ions, atoms or molecules and their transport into the solvent.
Dissolution testing is a critical preformulation solubility analysis research tool in the process of drug discovery that entails measuring the stability of the investigational product, achieving uniformity in production lots and determining its in vivo availability. Thus this Dissolution testing is an essential requirement for the development, establishment of in vitro dissolution and in vivo performance (IVIVR), registration and quality control of different dosage forms.
Dissolution testing has almost had a century of development. It expanded over years beyond the ordinary Tablets and Capsules, first to Extended-release and Delayed-release (enteric-coated) articles, then to transdermals, Multivitamin and Minerals products, and to Class Monographs for non-prescription drug combinations. It was in the year 1897 that Noyes and Whitney published a paper on "Rate of solution of solid substances in their own solution" which gave the first known reference to dissolution testing. In this paper, they suggested that a layer of saturated solution that forms instantly around a solid particle controls the dissolution rate. Later in 1900, Brunner and Tolloczko proved and listed the factors determining the dissolution rate as chemical and physical structures of the solid, the surface area exposed to the medium, agitation speed, medium temperature and the overall design of the dissolution apparatus. In 1904, Nernst and Brunner established a relationship between the dissolution rate and the diffusion coefficient by developing a modified Noyes-Whitney equation with the application of Fick's law of diffusion to it. In 1930, Experiments on dissolution testing began with in vivo-In vitro correlations and in 1931, Hixon and Crowell developed the cube-root law of diffusion. In 1934, disintegration test was introduced for tablets by the Swiss Pharmacopoeia Helvetica but it became an official United States Pharmacopoeia (USP) method only in 1950. During this period, the emphasis also moved from studying the effects of physicochemical properties of drug on dissolution to correlation of dissolution to bioavailability of dosage forms. In 1958, a rotating bottle dissolution method was developed for extended release formulations. The USP recognized a need for a standardized dissolution test and began experimenting with a variety of basket and stirring devices during the 1960s.Levy and Hayes4 utilized a beaker blade stirrer at 30-60rpm and found significant differences in the in vitro dissolution rates of different brands of aspirin tablets which linked to the incidence of gastric irritation caused by various brands due to their slow dissolution rates. The first official dissolution test for solid dosage forms using a rotating basket was incorporated by USP 18 in 1970. In 1975, the USP began developing of calibrators for dissolution testing and in 1978, it proposed three calibrator tablets - prednisone (disintegrating), salicylic acid (non-disintegrating) and nitrofurantoin (disintegrating), but no predefined calibration frequency was made. In the same year 1978, the Food Drug Administration (FDA) published guidelines for Dissolution Testing. In 1990, the paddle over disk, rotating cylinder and the Reciprocating Disk dissolution apparatus models were developed and later in 1995, the reciprocating cylinder and the flow-through cell were developed.
Dissolution testing is widely used in the pharmaceutical industry for optimization of formulation and quality control.
It is useful in the pharmaceutical and biotechnology industry to formulate drug dosage forms and to develop quality control specifications for its manufacturing process.
To identify the critical manufacturing variable, like the binding agent effect, mixing effects, granulation procedure, coating parameters and comparative profile studies.
- To comply with guidelines set in the scale up and post approval changes (SUPAC) and ICH.
- To select candidate formulation
- To simulate food effect on bio availability.
- To support waiver for bio equivalence requirements.
- In the study of Bio waivers.
- As a Surrogate for invivo studies.
- In the In vitro invivo correlations.
5. Historical Perspectives on Dissolution Technology. Available from: http://www.layloff.net/dissolution/1980Grady.pdf
6. Perspective On The History of Dissolution Testing. Available from: http://www.layloff.net/articles/Gradys%20Corner/A%20Perspective%20on%20t...
8. Jamzad, S and Fassihi R, Role of Surfactant and pH on Dissolution Properties of Fenofibrate and Glipizide--A Technical Note, AAPS PharmSciTech, 7(2), 2006, 33.