Cross-linking of hard gelatin carbamazepine capsules: effect of dissolution conditions on in vitro drug release

• Published in: European journal of pharmaceutical sciences 2003-06, Vol.19 (2), p.129-132
• Main Authors: Marchais, Hervé, Cayzeele, Guillaume, Legendre, Jean-Yves, Skiba, Mohamed, Arnaud, Philippe
• Format: Article
• Language: English
• Subjects: Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Capsules; Carbamazepine; Carbamazepine - chemistry; Carbamazepine - pharmacokinetics; Cross-linking; Cross-Linking Reagents - chemistry; Cross-Linking Reagents - pharmacokinetics; Dissolution with sodium lauryl sulfate; Enzymes; Gelatin; General pharmacology; Hard gelatin capsule; Medical sciences; Neuropharmacology; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Solubility
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/S0928-0987(03)00070-8

The aim of this study was to determine if the use of both enzyme and surfactant in the dissolution medium changes the in vitro drug release from cross-linked hard gelatin capsules containing a water-insoluble drug. Hard gelatin capsules were cross-linked by a controlled exposure to formaldehyde resulting in different stressed capsules and carbamazepine (CBZ) was chosen as a drug model. In vitro dissolution studies were conducted using simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) with enzymes. Sodium lauryl sulfate (SLS) was added in the dissolution medium at a concentration of 2% m/v both in SGF and SIF with pepsin and pancreatin, respectively. The percentage of CBZ dissolved was reduced by increasing the degree of gelatin cross-linking. For unstressed hard gelatin capsules, 36% of the CBZ was released after 1 h, lowering to 5% for highly stressed hard gelatin capsules in the SGF. A similar effect was observed with SIF. In the case of moderately stressed hard gelatin capsules, addition of enzyme in the dissolution medium enhanced the percentage of CBZ dissolved. The dissolution level increased from 12% to 39% in SGF with pepsin for hard gelatin capsules cross-linked with 1500 ppm formaldehyde. On the contrary, the use of enzyme in the dissolution medium did not increase the dissolution of CBZ from highly stressed hard gelatin capsules. Surprisingly, the addition of SLS in the medium did not allow the release of the CBZ both in SGF and in SIF. The results of this study demonstrate that the use of enzyme in the dissolution medium is justified for moderately cross-linked hard gelatin capsules. However, the action of a surfactant added in the medium containing enzyme remains unclear.