Calculation of the required size and shape of hydroxypropyl methylcellulose matrices to achieve desired drug release profiles

• Published in: International journal of pharmaceutics Vol. 201; no. 2; pp. 151 - 164
• Main Authors: Siepmann, Jürgen, Kranz, H, Peppas, N.A, Bodmeier, R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.05.2000; Elsevier
• Subjects: Algorithms; Biological and medical sciences; Chlorpheniramine - administration & dosage; Chlorpheniramine - chemistry; Controlled release; Delayed-Action Preparations; Drug Carriers - chemistry; General pharmacology; Geometry; Hydrophilic matrix; Hydroxypropyl methylcellulose; Lactose - analogs & derivatives; Lactose - chemistry; Medical sciences; Methylcellulose - analogs & derivatives; Methylcellulose - chemistry; Modeling; Models, Theoretical; Oxazines; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Propranolol - administration & dosage; Propranolol - chemistry; Reproducibility of Results; Geometry; Hydrophilic matrix; Hydroxypropyl methylcellulose; Modeling; Controlled release; Particle size; Pharmaceutical technology; Controlled release form; Control release polymer; Chemical structure; Drug carrier; Forecast model; In vitro; Dosage form; Active ingredient; Tablet; Particle shape; Chemical properties; Mathematical model; Release; Physicochemical properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(00)00390-2

The aim of this study was to develop methods for the design of hydroxypropyl methylcellulose (HPMC) tablets with specified drug profiles. This was achieved by the use of a mathematical model developed to predict the release kinetics of water-soluble drugs from HPMC matrices. The required model parameters were determined experimentally for propranolol HCl and chlorpheniramine maleate in 0.1 N HCl and phosphate buffer pH 7.4, respectively. Then, the effects of the dimensions and aspect ratio (radius/height) of the tablets on the drug release rate were evaluated. Independent experiments were conducted to verify the theoretical predictions. Acceptable agreement between theory and experiment was found, irrespective of the type of release medium and drug. However, statistical analysis revealed a structure in the resulting residuals. Drug release rates are overestimated at the beginning and underestimated at the end of the process. Possible explanations and modifications of the model are thoroughly discussed. Both, theoretical and experimental data showed that a broad spectrum of drug release patterns can be achieved by varying the size and shape of the tablet. The effect of the initial matrix radius on release was found to be more pronounced than the effect of the initial thickness. The practical benefit of the proposed method is to predict the required size and shape of new controlled drug delivery systems to achieve desired release profiles, thus significantly facilitating the development of new pharmaceutical products.