Crystal engineering of valproic acid and carbamazepine to improve hygroscopicity and dissolution profile

Abstract

Sodium valproate, the most common solid form of valproic acid, is highly hygroscopic and carbamazepine has extremely low aqueous solubility. Producing a salt form of valproic acid with tromethamine and a cocrystal form of valproic acid with carbamazepine have been studied as two approaches to improve physicochemical properties of the intended drugs. Characterization methods including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR) are applied to characterize the synthesized salt and cocrystal. The stability of sodium valproate and tromethamine valproate were examined in 33, 53, 75 and 100 percent of relative humidity. The dissolution profile studies were performed in phosphate buffer media (pH = 6.8) for carbamazepine (a low soluble drug) and carbamazepine-valprocic acid cocrystal. Tromethamine valproate was physically more stable than sodium valproate in exposure to humidity. Carbamazepine-valproic acid cocrystal did not show an extreme improvement in dissolution profile when compared with carbamazepine, however after 24 hcocrystal was more soluble.

Keywords:

• Carbamazepine
• valproic acid
• cocrystal
• salt

Acknowledgments

This article is resulted from Pharm D. thesis No. 4128 registered at Faculty of Pharmacy, Tabriz University of Medical Sciences. Also we thank PXRD lab, Institute of Mineralogy, north western regional office, Tabriz, Iran for providing PXRD patterns.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

A.S. would like to thank Vice Chancellor for Research of Tabriz University of Medical Sciences for the financial support of the project (60049).