Let’s look at the history of dissolution testing, starting from the beginning.
It all started in 1897 with the first reference to dissolution: Noyes and Whitney publish a paper on “The Rate of Solution of Solid Substances in Their Own Solution.” They suggested that the dissolution rate was controlled by a layer of saturated solution that forms instantly around a solid particle.
A few years later in 1900, Brunner and Tolloczko proved that dissolution rate depended on the chemical, physical structures of the solid, the surface area exposed to the medium, agitation speed, medium temperature and the overall design of the dissolution apparatus.
1904-Nernst and Brunner modified the Noyes-Whitney equation by applying Fick’s law of diffusion. A relationship between the dissolution rate and the diffusion coefficient was established.
1906; Pure Food and Drug Act; Passed in response to exposure of a large number of cases of unsanitary conditions, frauds, and drug marketing abuses e.g. (cough syrups that contained cocaine and opium) at the turn of the century.
1930-Experiments begin with in vivo-In vitro correlations.
1931-Hixon and Crowell develop the cube-root law of diffusion.
1934-Switzerland’s Pharmacopeia Helvetica was the first regulatory body to introduce a disintegration test for tablets.
1938; Food, Drug, and Cosmetic Act The first legislation that mandated drug manufacturers to test their products for safety. This initiative was passed in the aftermath of the Elixir of Sulfanilamide tragedy which killed 107 people mostly infants in 1938. A pharmaceutical company in Tennessee marketed Sulfanilamide (a recently developed antibacterial drug) against strep throat infections for children as a syrup using diethylene glycol (antifreeze) as solvent. This solvent is lethal and this drug was never tested for safety. (The only way that the FDA was able to seize the drug was on the grounds that it was mislabeled; ‘elixir’ is defined as a product dissolved in alcohol.) The most important aspect of the law; – it forbade the sale of any drug unless the FDA found it to be safe.
1950′s-Emphasis moved from studying the effects of physiochemical properties of drugs on dissolution to correlation of dissolution to bioavailability of dosage forms.
1950-Disintegration became an official USP Method, USP 14.
1951-Edwards suggested that the analgesic activity of aspirin can be manipulated by its rate of dissolution within the GI tract.
1958-The rotating bottle method was developed to study extended release formulations.
1960′s-Although it was recognized that disintegration was a critical process, deaggregation was essential for bioavailability. USP recognized a need for a standardized dissolution test. The USP began experimenting with a variety of basket and stirring devices.
1960-Levy and Hayes, utilizing a beaker and a three blade stirrer at 30-60 RPM, found significant differences in the in vitro dissolution rates of different brands of aspirin tablets and linked them to the incidence of gastrointestinal irritation caused by various brands due to their slow dissolution rates.
1962: Proof of Efficacy: the Kefauver-Harris Act. An OTC sedative from Hoechst, thalidomide caused thousands of birth defects in Europe before it was banned. Although the tough FDA standards kept thalidomide from being sold here, some got out via free samples distributed to MDs.
In 1962 congress passed the first major amendment to the 1938 law, legislating that in addition to safety, the industry would now have to prove the effectiveness of drugs it was seeking to market. This legislation was not confined to new drugs but extended to existent drugs.
1970- USP 18 incorporated the first official dissolution test for solid dosage forms. Twelve Monographs published in USP-NF with the official dissolution test- a rotating basket.
1970′s-Scientist find great variation in dissolution results from one apparatus to another. USP and FDA pushed for standardization of dissolution testing.
1970 Controlled Substances Act: Legislation that set rules for the manufacture and distribution of drugs considered to have potential of abuse.
1970 Efficacy screening covered 4000 drugs introduced between 1938-1962. Only 760 of these (19% of the drugs reviewed) were considered “even possibly effective”.
1975-USP begins development of calibrators for dissolution testing.
1978-FDA publishes ?Guidelines for Dissolution Testing?
USP proposes three calibrator tablets
Prednisone (disintegrating), Salicylic Acid (Non-disintegrating), Nitrofurantoin (disintegrating), but no predefined calibration frequency.
1981 FIP guideline
1984 Drug Price Competition and Patent Restoration Act Portent for coming legislation.
1988 USP: classification of IVIVC
1988 Food Effects
1990-Paddle over disk
1990 Nutrition Labeling and Education Act (NLEA).
1992 Accelerated FDA approval of drugs for life threatening or severely debilitating disease.
1994 FDA: SUPAC-IR
Flow through cell
1995: USP chapter 1088
1997-Pharmacia and Upjohn decided that it would no longer make USP Calibrator tablets
1997-USP Reformulated Prednisone tablets with the University of Maryland.
1997-USP extended upper range of Salicylic Acid.
1997 Fip: Guidelines Final Version
1997 FDA: SUPAC-MR
1997 FDA: Guidance ER IVIVC
1998-USP proposed reduction in chemical calibration and increase of mechanical calibration parameters.
1998-Mechanical Calibration Protocol Study commenced.
Volume 5, Issue 4, November 1998 Dissolution Tests for ER Products Barbara Sievert and Dr. Martin Siewert Hoechst Marion Roussel AG Frankfurt, Germany
Literature cited: DDG; material was presented by Bryan Crist during the May 1999 meeting of the DDG in Raleigh North Carolina
USP fundamentals of dissolution course. 2000