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. Precise control of polymorphs and pseudopolymorphs is important to obtain highly functional crystals in industry. The effect of a defined amount of amino acid additives on the pseudopolymorphism of L-arginine hydrochloride (LAHCL) is evaluated. A very small amount of specific amino acids is sufficient to stabilize the anhydrate form of LAHCL crystals at low temperature.