Basic Drug-Enterosoluble Polymer Coevaporates: Development of Oral Controlled Release Systems

• Published in: Drug development and industrial pharmacy Vol. 30; no. 8; pp. 847 - 857
• Main Authors: Govindarajan, Ramprakash, Nagarsenker, Mangal S.
• Format: Journal Article
• Language: English
• Published: Colchester Informa UK Ltd 01-01-2004; Taylor & Francis
• Subjects: Administration, Oral; Basic drug; Biological and medical sciences; Cellulose - analogs & derivatives; Cellulose - chemistry; Cellulose - pharmacokinetics; Chemistry, Pharmaceutical - methods; Coevaporates; Crystallization; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Diffusion - drug effects; Eudragit L100; Excipients - chemistry; Excipients - pharmacokinetics; Gastric Juice - drug effects; Gastric Juice - physiology; General pharmacology; Hydrogen-Ion Concentration; Intestinal Secretions - drug effects; Intestinal Secretions - physiology; Medical sciences; Oral controlled release; Particle Size; Pellets; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasticizers - chemistry; Plasticizers - pharmacokinetics; Polymers - chemistry; Polymers - pharmacokinetics; Polymethacrylic Acids - chemistry; Polymethacrylic Acids - pharmacokinetics; Tablets; Technology, Pharmaceutical - methods; Verapamil - pharmacokinetics; Verapamil HCl; Volatilization; Dosage form; Pharmaceutical technology; Controlled release form; Control release polymer; Base; Oral administration
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1081/DDC-200034572

Precipitation of basic drugs within oral prolonged release systems, at the higher pH values of the intestine, would affect drug release. Coevaporates of a model basic drug verapamil HCl, in single or mixed polymer systems, containing Eudragit L100 (L100) and ethyl cellulose or Eudragit RS100, were prepared from ethanolic solution. XRD and DSC indicated loss of crystallinity of the drug in the coevaporates. The presence of the enterosoluble polymer in the system was found to aid in faster dissolution of the drug at higher pH values. This was affected by the presence and type of retarding polymer present in the system. Compression of the coevaporates resulted in either very slow release of the drug or undesirable changes in the release profile. Pelletization of a coevaporate containing drug and L100 yielded systems, which released the drug uniformly when studied by the buffer change method in simulated gastric (SGF) and intestinal (SIF) fluids. The presence of L100 in intimate contact with the drug was found to be essential for the desirable drug release properties of the system. The drug release occurred predominantly by diffusion in SGF and by a combination of diffusion and polymer dissolution erosion in SIF. Appropriate choice of release modifiers and formulation variables and development of suitable formulations can yield systems which compensate for the reduced solubility of the drug in the higher pH environments of the intestine.