Cocrystallization of Pyridoxine (vitamin B 6 ) with several biologically important molecules was undertaken with the intent of successfully designing various hydrogen bonded adducts such as salts, cocrystals and eutectics. Pyridoxine formed eutectics with isoniazid (an anti-tubercular drug) and nicotinic acid (vitamin B3) and molecular salts with para-aminobenzoic acid (a bioactive) and saccharin (an artificial sweetener), respectively, in accordance to our design strategy. A salt cocrystal, precisely conjugate acid-base (CAB) cocrystal, was obtained for pyridoxine-para-nitrobenzoic acid combination. The role of supramolecular affinity of hydrogen bonding functional groups and ∆pK a differences' leading to the formation of above diverse adducts was discussed. This study underpins the need for full-fledged supramolecular compatibility studies of multi-vitamin/drug combinations towards the development of optimal and/or synergistic combination formulations.
IntroductionPyridoxine (abbreviated as PN, Figure 1), a form of vitamin B 6 , is an essential organic nutrient which serves in many vital metabolic activities of living cells. 1 It is co-administered with several other B-complex vitamins and vitamin C in multi-vitamin therapy. Further, PN is advocated for prophylactic/supplemental use in tuberculosis treatment to prevent isoniazid-induced neuropathy. 1,2 It is administered as its hydrochloride salt in dietary and clinical conditions. 1 Xray crystal structures were available for PN 3 and several of its salts including the hydrochloride salt. 4 Despite its combination with several vitamins and anti-tubercular drug isoniazid in various pharmaceutical formulations, only few studies on its interactions/compatibility with the latters were undertaken in the literature. 5 Cocrystallization studies serve as an important methodology to probe the physical and supramolecular compatibility of a given combination, particularly multi-nutrient/drug combinations, and achieve an optimal formulation for the combination. [6][7][8][9][10][11][12][13][14][15][16][17][18][19] Friščić et al. emphasized the biological and pharmaceutical significance of cocrystallization through their studies on steroid hormones. 20,21 In their recent review, Sinha et al. 6 noted that in spite of the importance of cocrystallization studies on vitamins, they were found to be least explored. In this background, we have performed cocrystallization of PN with nicotinic acid (vitamin B 3 ), bioactive para-aminobenzoic acid and anti-tubercular drug isoniazid among other compounds (Figure 1). Although it is more practical to study the cocrystallization behavior of PN hydrochloride salt, native pyridoxine with innocent pyridine N group amenable for molecular salt 22-27 /cocrystal formation was studied. The partner molecules for cocrystallization with PN were selected on the bottom line to corroborate the hypothesis that continuity of heteromolecular interactions leads to salt/cocrystal formation and discontinuity results in the eutectic for a particular combinati...