Immediate Drug Release from Solid Oral Dosage Forms

• Published in: Journal of pharmaceutical sciences Vol. 94; no. 1; pp. 120 - 133
• Main Authors: Schreiner, Thomas, Schaefer, Ulrich F., Loth, Helmut
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.01.2005; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Algorithms; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Biological and medical sciences; dissolution; Dosage Forms; Drug Compounding; Excipients; formulation; General pharmacology; Ketoprofen - administration & dosage; Kinetics; mathematical model; Medical sciences; Models, Statistical; Pharmaceutical Preparations - administration & dosage; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Porosity; Powders; Solubility; Spectrophotometry, Ultraviolet; Stearic Acids; Surface Properties; unit operations; Water; mathematical model; formulation; kinetics; excipients; unit operations; dissolution; Drug; Pharmaceutical technology; Vehicle(excipient); Oral form; Dissolution; Formulation; Dosage form; Solid form; Kinetics; Mathematical model; Release
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.20226

Fast drug release from solid dosage forms requires a very fast contact of the vast majority of the drug particles with the solvent; this, however, is particularly delayed in tablets and granulations. Starch and cellulose substances favor the matrix disintegration during the starting phase and the generation of the effective dissolution surface of the drug substance, thereby. To investigate the very complex interrelation between the functionality of commonly used excipients and the structural effects of the production processes, wettability, porosity, water uptake, and drug release rates of several ketoprofen‐excipient preparations (powder blends, granulations, tablets) were measured. Significant linear correlation between these parameters, however, was not achieved; only qualitative tendencies of the effects could be detected. In consequence, a general mathematical model describing the mechanistic steps of drug dissolution from solid dosage forms in a fully correct way was not realized. However, the time‐dependent change of the effective dissolution surface follows stochastic models: a new dissolution equation is based on the differential Noyes‐Whitney equation combined with a distribution function, e.g. the lognormal distribution, and numerically solved with the software system EASY‐FIT by fitting to the observations. This new model coincides with the data to a considerably higher degree of accuracy than the Weibull function alone, particularly during the starting, matrix disintegration, and end phases. In combination with a procedure continuously quantifying the dissolved drug, this mathematical model is suitable for the characterization and optimization of immediate drug release by the choice and modification of excipients and unit operations. The interdependence of some characteristic effects of excipients and production methods is discussed.