Sucralose as co-crystal co-former for hydrochlorothiazide: development of oral disintegrating tablets

• Published in: Drug development and industrial pharmacy Vol. 42; no. 8; pp. 1225 - 1233
• Main Authors: Arafa, Mona F., El-Gizawy, Sanaa A., Osman, Mohamed A., El Maghraby, Gamal M.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-08-2016
• Subjects: Administration, Oral; Chemistry, Pharmaceutical; Co-crystallization; co-grinding; Crystallization; dissolution efficiency; Drug Carriers - chemistry; Drug Liberation - physiology; Excipients - chemistry; fast dissolving; Hydrochlorothiazide - chemistry; hydrochlorothiazide crystals; Solubility; Spectroscopy, Fourier Transform Infrared - methods; sucralose; Sucrose - analogs & derivatives; Sucrose - chemistry; sweetener; Tablets - chemistry; Taste; X-Ray Diffraction - methods; dissolution efficiency; co-grinding; sucralose; sweetener; Co-crystallization; fast dissolving; hydrochlorothiazide crystals
• ISSN: 0363-9045; 1520-5762
• DOI: 10.3109/03639045.2015.1118495

Development of oral disintegrating tablets requires enhancement of drug dissolution and selection of sweetener. Co-crystallization of drugs with inert co-former is an emerging technique for enhancing dissolution rate. The benefit of this technique will become even greater if one of the sweeteners can act as co-crystal co-former to enhance dissolution and mask the taste. Accordingly, the objective of this work was to investigate the efficacy of sucralose as a potential co-crystal co-former for enhancing the dissolution rate of hydrochlorothiazide. This was extended to prepare oral disintegrating tablets. Co-crystallization was achieved after dissolving hydrochlorothiazide with increasing molar ratios of sucralose in the least amount of acetone. The co-crystallization products were characterized using Fourier transform infrared spectroscopy, differential thermal analysis and powder X-ray diffraction. These measurements indicated that co-crystallization process started at a drug sucralose molar ratio of 1:1 and completed at 1:2. The developed co-crystals exhibited faster drug dissolution compared with the control, with co-crystal containing the drug with sucralose at 1:2 molar ratio being optimum. The later was used to prepare fast disintegrating tablets. These tablets had acceptable physical characteristics and showed fast disintegration with subsequent rapid dissolution. The study introduced sucralose as co-crystal co-former for enhanced dissolution and masking the taste.