Cocrystal habit engineering to improve drug dissolution and alter derived powder properties

• Published in: Journal of pharmacy and pharmacology 2016-05, Vol.68 (5), p.665-677
• Main Authors: Serrano, Dolores R., O'Connell, Peter, Paluch, Krzysztof J., Walsh, David, Healy, Anne Marie
• Format: Article
• Language: English
• Subjects: Acedapsone - chemistry; Acetone - chemistry; Aerosols; Aminosalicylic Acid - chemistry; Anti-Infective Agents - chemistry; cocrystal habit; Crystallization; Crystallography, X-Ray; Crystals; dissolution; Drug Combinations; Drug Compounding; Ethanol - chemistry; flowability; Habits; Kinetics; Microscopy, Electron, Scanning; Models, Chemical; Models, Molecular; Powder Diffraction; Powders; Solubility; Solvents - chemistry; Surface Properties; tabletability; Technology, Pharmaceutical - methods; wettability; X-rays
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12476

Objectives Cocrystallization of sulfadimidine (SDM) with suitable coformers, such as 4‐aminosalicylic acid (4‐ASA), combined with changes in the crystal habit can favourably alter its physicochemical properties. The aim of this work was to engineer SDM : 4‐ASA cocrystals with different habits to investigate the effect on dissolution, and the derived powder properties of flow and compaction. Methods Cocrystals were prepared in a 1 : 1 molar ratio by solvent evaporation using ethanol (habit I) or acetone (habit II), solvent evaporation followed by grinding (habit III) and spray drying (habit IV). Key findings Powder X‐ray diffraction showed Bragg peak position was the same in all the solid products. The peak intensity varied, indicating different preferred crystal orientation confirmed by SEM micrographs: large prismatic crystals (habit I), large plate‐like crystals (habit II), small cube‐like crystals (habit III) and microspheres (habit IV). The habit III exhibited the fasted dissolution rate; however, it underwent a polymorphic transition during dissolution. Habits I and IV exhibited the highest Carr's compressibility index, indicating poor flowability. However, habits II and III demonstrated improved flow. Spray drying resulted in cocrystals with improved compaction properties. Conclusions Even for cocrystals with poor pharmaceutical characteristics, a habit can be engineered to alter the dissolution, flowability and compaction behaviour.