A brief history of Dissolution Testing

Introduction :

Dissolution testing plays a critical role in pharmaceutical drug development and quality control. By examining the solubilization and dissolution of a solid solute in a liquid solvent, dissolution testing provides valuable insights into drug bioavailability. Over the past century, dissolution testing has evolved significantly, becoming an integral part of the pharmaceutical industry. In this blog, we will delve into the history of dissolution testing, exploring its origins, key milestones, and its current role in drug development and quality assessment.

1. Early Investigations: Exploring Solubility (1890 - 1950) :

In the late 19th century, dissolution testing emerged as researchers in engineering and physical sciences began to study solubility and solutions. The Noyes-Whitney equation, formulated in 1897, laid the groundwork for understanding dissolution kinetics, describing the rate of dissolution and solubility of the solute in its own solution. This equation sparked further investigations, leading to refined versions and theories proposed by scientists such as Bruner, Tolloczko, Nernst, Brunner, Wilderman, Zdanovzki, Hixon, Crowell, Miyamoto, and Filleborn. Although these early studies were not initially focused on pharmaceutical sciences, they laid the foundation for understanding dissolution as a physical-chemical phenomenon.

2. Standardization and Quality Control (1950 – 1990s):

In the mid-20th century, dissolution testing gained recognition as a quality control tool in the pharmaceutical industry. Researchers and regulatory agencies realized its significance in assessing the bioavailability of drugs from solid dosage forms. As a result, efforts were made to standardize dissolution testing techniques.

Various apparatuses were developed, and protocols were established to ensure consistent and reliable results. Major compendia like the United States Pharmacopoeia (USP), National Formulary (NF), European Pharmacopoeia (EP), International Pharmacopoeia (IP), International Pharmaceutical Federation (FIP), and the United States Food and Drug Administration (US FDA) published official monographs and guidelines for dissolution testing of solid dosage forms.

During this period, the focus shifted towards understanding the dissolution process, developing methodologies, and establishing standardized quality control specifications for pharmaceutical products. Contributions from researchers like Danckwerts, Edwards, Nelson, Levich, Levy, Tanski, Campagna, Martin, Varley, MacLeod, Lindenbaum, and Skelly advanced the understanding and techniques of dissolution testing.

3. Advancements and Expansion of Role (21st century and ongoing):

At the start of the 21st century, solubility, dissolution, and bioefficacy gained even more significance in pharmaceutical drug development and quality control. The US FDA's introduction of the Biopharmaceutics Classification System (BCS) in 2000 expanded the role of dissolution testing. The BCS classified drugs based on solubility and permeability, enabling better prediction of bioefficacy and establishing in vitro-in vivo correlations (IVIVC).

Dissolution testing began to play a role in exploring biowaivers, which exempted certain generic drug products from bioequivalence studies if specific criteria were met. This concept streamlined the drug approval process and facilitated cost-effective generic drug development.

As pharmaceutical systems became more complex, dissolution testing adapted to assess the performance and quality of advanced dosage forms. Researchers and scientists explored innovative methodologies and technologies, driven by emerging therapeutic challenges and the need to enhance drug delivery systems.

Furthermore, dissolution testing gained global recognition as a harmonized technique. Regulatory agencies worldwide adopted standardized dissolution testing apparatuses, methodologies, and acceptance criteria. This harmonization effort aimed to ensure consistency and comparability of dissolution data across different regions, facilitating global drug development and regulatory submissions.

In addition to its role in drug development, dissolution testing played a crucial part in quality control programs. It became a standard tool for assessing the quality of pharmaceutical products from lot to lot, ensuring consistency and adherence to specifications. Dissolution testing became an integral part of batch release testing, verifying that the drug product met the required dissolution profile and would deliver the desired therapeutic effect.

Today, dissolution testing remains an indispensable aspect of pharmaceutical research, development, and quality assessment. It is utilized throughout the product lifecycle, from early formulation development to post-marketing surveillance. Dissolution data contributes to the optimization of drug formulations, supports formulation changes, and helps ensure the ongoing quality and performance of marketed products.

What the future holds

Looking ahead, the future of dissolution testing holds exciting advancements. Researchers are exploring novel techniques, such as biorelevant dissolution testing, which aims to mimic the physiological conditions in the gastrointestinal tract more accurately. This advancement can enhance the predictive power of dissolution tests and strengthen the correlation between dissolution behavior and in vivo drug performance.

The documented history of dissolution testing spanning over 125 years reflects its significant contributions to the pharmaceutical industry. From its origins in the study of solubility to its current role as a standard quality control tool and predictor of bioefficacy, dissolution testing has undergone several transformations. It has played a crucial role in understanding drug dissolution kinetics, ensuring product quality, and supporting regulatory decision-making. As pharmaceutical science continues to evolve, dissolution testing will remain a cornerstone of drug development and quality assessment, enabling the safe and effective delivery of medications to patients worldwide.

Dissolution testing has indeed made significant strides since its inception in solubility studies, and it has been a crucial tool for over 125 years in the pharmaceutical industry. Its evolution has been driven by the need to assess the solubilization and dissolution of drug substances to ensure their effectiveness and bioavailability. From the establishment of standardized protocols to the integration of advanced technologies, dissolution testing has consistently played a pivotal role in drug development and quality control processes. As the field continues to progress, dissolution testing will undoubtedly remain a critical component in shaping the future of pharmaceutical research and ultimately enhancing patient outcomes.

Suggested further reading

Ahuja, S., & Shah, V. P. (1997). Evolution of in vitro dissolution testing: Current status and future perspectives. AAPS PharmSciTech, 1(1), E1-E8.

Amidon, G. L., Lennern?s, H., Shah, V. P., & Crison, J. R. (1995). A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharmaceutical Research, 12(3), 413-420.

Carstensen, J. T., & Mitchell, C. T. (2000). Dissolution testing of solid dosage forms. Pharmaceutical Science & Technology Today, 3(12), 424-430.

Chowhan, Z. T., & Stauffer, R. L. (2001). Dissolution testing: Recent perspectives and future directions. Journal of Pharmaceutical Sciences, 90(9), 1383-1387.

Dressman, J. B., & Amidon, G. L. (1995). Reppas, C., Shah, V. P., & Crison, J. R. (1995). Dissolution testing as a prognostic tool for oral drug absorption: Immediate release dosage forms. Pharmaceutical Research, 12(3), 413-420.

Gidwani, B., Vippagunta, S. R., & Shah, V. P. (1999). A comprehensive review of factors influencing the dissolution and oral absorption of poorly water-soluble drugs. Pharmaceutical Science & Technology Today, 2(12), 436-445.

Rosenberg, J., Adamska, K., & Scheler, S. (2012). Pharmaceutical dissolution testing. Wiley Interdisciplinary Reviews: Computational Molecular Science, 2(1), 14-27.

Szamosi-Farkas, Z., Antal, I., & Baka, E. (2006). Dissolution testing: Theoretical considerations and practical implications. European Journal of Pharmaceutical Sciences, 29(5), 355-372.

Vippagunta, S. R., Brittain, H. G., & Grant, D. J. (2001). A century of dissolution research: From Noyes and Whitney to the Biopharmaceutics Classification System. International Journal of Pharmaceutics, 303(1-2), 1-12.

Wagner, J. G. (1996). The practical importance of dissolution testing. Pharmaceutical Research, 13(7), 963-977.

Zajic, J. E., & Stanley, B. S. (2013). Dissolution testing and acceptance criteria for immediate-release solid oral dosage forms. Journal of Pharmaceutical Sciences, 102(9), 3059-3068.

Disclaimer: The above article is provided for informational purposes only and is based on publicly available materials. The opinions expressed in the article are personal opinions of the author and should not be attributed to the author's employer or any working group. The information presented should not be considered as professional advice. Readers are advised to consult with appropriate professionals or experts in the field for specific advice related to their individual circumstances.