Drug Dissolution: Fundamental Theoretic Models

ALAN TALEVI; MARÍA ESPERANZA RUIZ

The ADME Encyclopedia. A Comprehensive Guide on Biopharmacy and Pharmacokinetics

Springer

Lugar: Basel; Año: 2021; p. 1 - 9

Drug dissolution and drug release are fundamental processes in relation with therapeutic systems, as they constitute prerequisites for the absorption of a drug substance, thus being determinants of drug bioavailability. According to the IUPAC, ?dissolution? refers to the mixing of two phases with the formation of one new homogeneous phase (i.e., the solution) [1]. In the framework of pharmaceutics, the term drug dissolution generally refers to the process in which a substance in solid-state forms a solution; it is, therefore, a key process for the biopharmaceutical performance of solid dosage forms (e.g., tablets, hard capsules, pharmaceutical suspensions) and, in particular, those comprising poorly soluble substances. Drug dissolution is an integral part of preclinical and clinical development, including screening and physicochemical characterization of drug substances and product formulation [2]. Dissolution modeling is commonly used to rationalize the selection of dosage strengths and formulations. Dissolution testing constitutes a routine and highly relevant test in pharmaceutical quality control.Surface kinetics and mass transfer mechanisms on the solid-liquid interfaces are the cornerstone of drug dissolution models, and a significant amount of drug dissolution studies rely on the diffusion layer model originally conceived by Noyes and Whitney and expanded shortly after by Nernst and Brunner.It is important to differentiate drug dissolution from drug release, as these terms are usually used interchangeably but strictly speaking, denote different phenomena [3]. Dissolution has been clearly defined in the first paragraph of this entry. Drug dissolution generally encompasses five major mass transport steps: wetting of the solid particle surface; breakdown of solid-state bonds; solvation of the resulting individualized species (e.g., molecules); diffusion through an unstirred boundary layer; and convection within a well-stirred bulk solution (as observed in the gastrointestinal tract due to peristaltic and segmentation movements or in the stirred vessels of a drug dissolution apparatus). In contrast, the term drug release denotes a more complex phenomenon, with drug dissolution being just a part of it when the drug is delivered, initially, in the solid state (other common phenomena at play in drug release include penetration of water into the drug delivery system, swelling, disintegration, erosion, drug partition between immiscible phases, etc.).