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Dissolution research started more than a century ago in the field of physical chemistry and went through several significant developments since. Yet, the explicit attention in drug-related dissolution has only started growing in the 1950s, after the researchers realized that drug release from orally administered solid pharmaceutical formulations significantly influences the bioavailability. Researches show that solubility and permeability of the drugs are key factors in the correlation between the in vitro examination and the in vivo determinations (IVIVC). This review aims to summarize the most relevant developments in chronological order, ranging from simple disintegration studies to biorelevant methods. Biorelevant methods can be used to recognize the effects of food on dissolution, as well as to identify solubility limitations and stability issues. The development of a biologically relevant dissolution method for oral dosage forms needs to take the physiological conditions of the gastrointestinal (GI) tract into account that may influence the drug dissolution. This review presents the simplest dissolution media, the composition of biorelevant media simulating gastrointestinal fluids, and the latest updates of the field.

Purpose The aim of our work was to develop a biorelevant dissolution method for a better understanding of the in vivo performance of delayed-release tablet formulations. Methods The typical pH profile and residence times in the stomach and small intestine were determined in fasted conditions based on the published results of swallowable monitoring devices. Then, a multi-stage pH shift dissolution method was developed by adding different amounts of phosphate-based buffer solutions to the initial hydrochloric acid solution. Because of the highly variable in vivo residence times in the stomach, two alternatives of the method were applied, modeling rapid and slow gastric emptying as well. This approach provided an opportunity to study the effect of the acidic treatment on post gastric release. Six enteric-coated low-dose acetylsalicylic acid (ASA) formulations including the reference Aspirin Protect were tested as a model compound. Moreover, the thickness of the coating of each formulation was investigated by scanning electron microscope. Results Comparing the in vitro results to the known properties of the formulations, the new method was found to be more discriminative than the USP dissolution method. Ingredients affecting the in vitro dissolution, and thus probably the in vivo performance, were identified in both the tablet core and the coating of the tested formulations. The limited available in vivo data also indicated an increased predictivity. Conclusion Overall, the presented method may be an efficient tool to support the development of enteric coated generic formulations. Graphical abstract