Development of orally disintegrating tablets containing solid dispersion of a poorly soluble drug for enhanced dissolution: In-vitro optimization/in-vivo evaluation

• Published in: PloS one Vol. 15; no. 12; p. e0244646
• Main Authors: Fouad, Shahinaze A, Malaak, Fady A, El-Nabarawi, Mohamed A, Abu Zeid, Khalid
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.12.2020; Public Library of Science (PLoS)
• Subjects: Absorption; Administration, Oral; Analgesics; Animals; Anthraquinones - administration & dosage; Anthraquinones - chemical synthesis; Anthraquinones - pharmacokinetics; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - pharmacokinetics; Anti-inflammatory drugs; Arthritis; Bioavailability; Biological Availability; Biomedical materials; Capsules; Cartilage; Chemical properties; Colon; Cytokines; Disease; Disease Models, Animal; Disintegration; Dispersion; Dissolution; Drug therapy; Drugs; Edema; Edema - drug therapy; Edema - etiology; Efficiency; Excipients - chemistry; Inflammation; Male; Medicine and Health Sciences; Optimization; Oral cavity; Oral medication; Osteoarthritis; Osteoporosis; Pain; Pharmaceutical research; Pharmaceutical sciences; Pharmacy; Physical characteristics; Physical properties; Physical Sciences; Polyethylene glycol; Product development; Rats; Research and Analysis Methods; Side effects; Solubility; Surfactants; Tablets; Variance analysis; Wetting; Egypt; Giza Egypt
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0244646

Diacerein (DCN), a potent anti-inflammatory API used to treat osteoarthritis yet, it suffers from poor water solubility which affects its oral absorption. Unabsorbed colonic DCN is converted into rhein, which is responsible for laxation as a main side effect of DCN treatment. Therefore, in this study orally disintegrating tablets (ODTs) loaded with optimized DCN solid dispersion system were prepared using different co-processed excipients (Prosolv® ODT, Pharmaburst® 500 and F-melt®), aiming to achieve improved solubility, rapid absorption and consequently limited amount of rhein reaching the colon. Prepared ODTs were evaluated for physical characteristics, in-vitro drug release, disintegration and wetting times. Dissolution parameters; dissolution efficiency percent at 10 (DE (10 min)%) and 30 (DE (30 min)%) min and mean dissolution time (MDT) were determined. The optimized ODT showed 1.50 and 1.12 fold increase in DE (10 min)% and DE (30 min)%, respectively and 2 fold decrease in MDT, compared to Diacerein® capsules. In-vivo anti-inflammatory effect of optimized ODT, using rat paw edema revealed significant increase in edema inhibition (p < 0.0465) and promoted onset of action compared to Diacerein® capsules at 0.5 hr. It could be concluded that optimized ODT could be promising for enhanced dissolution and rapid absorption of DCN from the oral cavity.