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

Abstract

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.

Hydrophilic Sugars for Enhancing Dissolution Rate of Cilostazol: Effect of Wet Co-Processing

“…These changes were also reported by other investigators who treated the sugar in a similar way. 7,8 Additionally, these modifications in the diffraction pattern coincide with the DSC data that showed increase in the Tm value for the processed sucralose that would suggest formation of new crystalline structure. The diffractogram of unprocessed mannitol showed its crystalline structure as noted from the recorded diffraction peaks (Figure 3b and Table 4).…”

“…The adopted processing technique was similar to the previously reported method with slight modification. 6,8 Cilostazol was mixed with the calculated amount of sucralose or mannitol and ethanol was added gradually with grinding to form smooth paste using mortar and pestle. This paste was subjected to continuous grinding for 30 minutes to form a dry powder.…”

“…6,7 Xylitol was also employed to enhance the dissolution rate of felodipine. 8 Mannitol is another hydrophilic sugar showed promising efficacy in enhancing the dissolution rate of olanzapine and etoricoxib after solid dispersion formation and as cocrystal conformer for hydrochlorothiazide. [9][10][11] Hydrophilic polymers have been extensively employed to fabricate solid dispersion with hydrophobic drugs with the goal of enhancing their dissolution pattern.…”

Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review

“…Many co-crystallization techniques have been reported, including neat grinding (NG), liquid-assisted grinding (LAG), solvent evaporation (SE), gas anti-solvent precipitation (GAS), and many more [ 7 ]. Recently, the success of the “green method” for co-crystallization has prompted many researchers to seek other co-crystallization techniques that are more eco-friendly [ 8 ]. Mechanochemical reactions, including grinding without or with minimal solvents [ 9 ], have emerged as an efficient alternative for co-crystal synthesis due to their environmentally friendly process [ 10 ].…”

Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index

“…Furthermore DSR enhancement was also studied for Exemestane and Megestrol acetate acting as antineoplastics (Shiraki et al, 2008). Such interest was also focused on some cardiovascular agents including Cilnidipine, Felodipine, Irbesartan, Telmisartan, Apixaban, Ezetimibe, Fenofibrate, Olanzapine, Sildenafil, Tadalafil (Arafa et al, 2016;Chadha et al, 2014;Chen et al, 2016;Info, 2013;Khor et al, 2016;Nijhawan et al, 2015;Punita et al, 2016;Renkoğlu et al, 2015;Shewale et al, 2015;Shiraki et al, 2008;Sugandha et al, 2014;Vinesha et al, 2013;Žegarac et al, 2014). There are also single studies devoted to antiallergics as Fexofenadine (Mounika et al, 2015), antidiabetic agents as Gliclazide (Prawiro et al, 2016), AMG 517, Danazol, Famotidine (Bak et al, 2008;Childs et al, 2013;Shi et al, 2013), sodium channel blockers as 4-(4-…”