Xylitol as a potential co-crystal co-former for enhancing dissolution rate of felodipine: preparation and evaluation of sublingual tablets

• Published in: Pharmaceutical development and technology 2018-06, Vol.23 (5), p.454-463
• Main Authors: Arafa, Mona F, El-Gizawy, Sanaa A, Osman, Mohamed A, El Maghraby, Gamal M
• Format: Article
• Language: English
• Subjects: Administration, Oral; Anti-Arrhythmia Agents - administration & dosage; Anti-Arrhythmia Agents - chemistry; Calorimetry, Differential Scanning; Crystallization; Drug Liberation; Excipients - chemistry; Felodipine - administration & dosage; Felodipine - chemistry; Solubility; Spectroscopy, Fourier Transform Infrared; Tablets; X-Ray Diffraction; Xylitol - chemistry
• ISSN: 1083-7450; 1097-9867
• DOI: 10.1080/10837450.2016.1242625

Dissolution enhancement is a promising strategy for improving drug bioavailability. Co-crystallization of drugs with inert material can help in this direction. The benefit will become even greater if the inert material can form co-crystal while maintaining its main function as excipient. Accordingly, the objective of the current study was to investigate xylitol as a potential co-crystal co-former for felodipine with the goal of preparing felodipine sublingual tablets. Co-crystallization was achieved by wet co-grinding of the crystals deposited from methanolic solutions containing felodipine with increasing molar ratios of xylitol (1:1, 1:2 and 1:3). The developed co-crystals were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) before monitoring drug dissolution. These results reflected the development of new crystalline species depending on the relative proportions of felodipine and xylitol with complete co-crystallization of felodipine being achieved in the presence of double its molar concentration of xylitol. This co-crystal formulation was compressed into sublingual tablet with ultrashort disintegration time with subsequent fast dissolution. Co-crystal formation was associated with enhanced dissolution with the optimum formulation producing the fastest dissolution rate. In conclusion, xylitol can be considered as a co-crystal co-former for enhanced dissolution rate of drugs.