Crystal Growth and Physical Characterization of Acyclovir Crystallized with Ascorbic Acid and Zinc Chloride

Abstract

Acyclovir is the API in the most common antiviral drug used for treatment of HSV and VZV infections. Advantages for acyclovir are low cytotoxicity and low HSV resistance as well as the availability of low cost generic forms. Disadvantages include low bioavailability, perhaps partially due to low solubility. Herein, we present cocrystallization of acyclovir with ascorbic acid and zinc chloride forming a new complex. Acyclovir was separated from an acyclovir drug and the cocrystals of 1:1:1 acyclovirascorbic acid-ZnCl 2 , ACV-ASc-Zn) were screened by slow evaporation via solution-based methods under 10 solvents. Successful cocrystal forms in the solvent isopropanol-water (1:2). Physical properties were characterized by SEM/EDX, FT-IR and TGA. 

Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative Activity

“…Vitamin C was previously involved as coformer in the formation of cocrystals (Kovac-Besovic et al, 2009; Meepripruk et al, 2016); moreover, its antioxidant activity could synergistically combine with the intrinsic antioxidant effect of BA thus leading to a more soluble and higher biologically active cocrystal. Another key element in cocrystallization is the selection of solvents which depends on the solubility of both drug and coformer and strongly influences the stoichiometry of the resulting cocrystal (Leyssens et al, 2014).…”

“…As an example, the apparent solubility of vitamin K3 was greatly increased by cocrystallization with naphtoic acids and sulfamerazine (Zhu et al, 2015). Vitamin C was successfully employed as coformer in the cocrystallization of acyclovir for the purpose of improving the latter's water solubility and bioavailability (Meepripruk et al, 2016). Therefore, we presume that the experimental data reported here that revealed a very strong cytotoxic effect of BA+VitC cocrystals as compared to previously and currently reported data for BA alone are partially due to an increased water solubility of BA as a result of vitamin C cocrystallization; moreover, the presence of vitamin C as coformer may lead to an optimized bioavailability, subject that needs however further investigations.…”

Novel Adducts of Acyclovir with 2,6-Dihydroxybenzoic Acid: Synthesis and Structural, Theoretical, and Spectroscopic Analyses

“…Among the coformers used for ACV cocrystallization, there are GRAS substances, 18 i.e., nicotinamide, 19 L-tartaric acid, 14 succinic acid, 20 L-ascorbic acid, and zinc chloride. 6 Interestingly, the use of maleic acid gives two polymorphic ACV-maleic acid salts, L and R. 21,22 In this paper, 2,6-dihydroxybenzoic acid (26DHBA) was used as a coformer for ACV cocrystallization (Figure 1).…”

“…The summary of the multicomponent systems containing ACV obtained so far, the methods of their preparation, and the influence on specific physicochemical properties is presented in Table S1. Among the coformers used for ACV cocrystallization, there are GRAS substances, i.e., nicotinamide, l -tartaric acid, succinic acid, l -ascorbic acid, and zinc chloride . Interestingly, the use of maleic acid gives two polymorphic ACV-maleic acid salts, L and R. , …”

“…3−5 On the other hand, it shows low cytotoxicity and low resistance to HSV, therefore the search for its other solid forms with improved physicochemical properties, i.e., solubility, dissolution profile, and bioavailability is extremely important. 6 Additionally, ACV is listed by the World Health Organization as one of the safest, most effective, and essential drugs in the basic healthcare system. 7 Various methods to increase the solubility of ACV have been used.…”