Effect of Specific Amino Acids on Controlling Crystal Pseudopolymorphism of L-Arginine Hydrochloride

The effect of a small amount of amino acid additives on the pseudopolymorphism of L-arginine hydrochloride (LAHCL) in aqueous solution is reported. Results confirm that L-alanine (L-Ala) has a stabilizing effect on the crystals of the anhydrate form of LAHCL at low temperature. Intriguingly, the stabilizing effect was observed even when L-Ala was added after a large amount of LAHCL had formed. In contrast, no stabilizing effect with D-Ala could be stated, suggesting that the stereochemistry of the additives is an important factor. In addition to the stereochemistry, also the length and bulkiness of the alkyl side-chain of the amino acids were found to be significant factors. Based on these results, a mechanism is proposed for stabilization of anhydrate LAHCL crystals by amino acid additives.