Polymorphism and pseudopolymorphism: Influencing the dissolution properties of the guanine derivative acyclovir

• Published in: International journal of pharmaceutics 1996-08, Vol.139 (1), p.231-235
• Main Authors: Kristl, A., Srčič, S., Vrečer, F., šuštar, B., Vojnovic, D.
• Format: Article
• Language: English
• Subjects: Acyclovir; Anhydrous acyclovir; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Dissolution behavior; Medical sciences; Pharmacology. Drug treatments; Polymorphic solvate; Pseudopolymorphic solvate; Solid-solid transformation
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/0378-5173(96)04601-7

In this work we established that acyclovir exists in hydrated form and that the ratio between acyclovir and water molecules in the crystal structure is 3:2. The anhydrous crystalline form of acyclovir was also prepared. Both crystalline forms were examined by means of thermal analyses, X-ray powder diffraction, infrared spectroscopy, solubility and dissolution rate studies. The differences in almost all tested parameters between the acyclovir hydrated and anhydrous forms were observed. They were explained by different crystal forms of the substances examined. It was found, that besides hydrate, two anhydrous forms of acyclovir are present: the unstable one, obtained at a drying temperature below 150°C (which converts to the hydrate almost immediately in the atmosphere), and the stable one, obtained at drying temperatures above 150°C (which shows, on heating to 172°C, the solid-solid transition). It was thus postulated that acyclovir can exist as a pseudopolymorphic and polymorphic solvate.