Glafenine hydrochloride

One promising approach to identify novel CFTR corrector structural classes is to screen compounds, already developed for other indications, for their ability to correct the trafficking defect of mutant CFTR. Following this approach, glafenine hydrochloride (17), miglustat (18), and SAHA (19) were recently described as promising CFTR corrector leads. 

Non - aqueous titration Glafenine (300 mg) is dissolved in 30 mL of acetic acid. The end point is detected potentiometrically. When glafenine hydrochloride is used, mercuric acetate is to be added to the titration medium. Each mL of 0.1M perchloric acid volumetric solution is equivalent to 37.28mg of glafenine. This method is applied for the drugs determination in tablets and suppositories (9). 

Glafenine has a solubility in water of 1 in 60,000 at pH 7. The rectal absorption of glafenine from an aqueous micro-enema, and of glafenine hydrochloride from a fatty suppository is extremely slow and incomplete, due to the low solubility of glafenine at the pH in the rectum [16]. Therefore this active substance is not effective after rectal administration, although glafenine suppositories were commercially available in the past century. On the contrary, for example, the solubility of phenobarbital in water of 1 in 1,000 is sufficient for rectal administration. 

---