Cocrystal habit engineering to improve drug dissolution and alter derived powder properties. (26th September 2015)

• Record Type: Journal Article
• Authors: Serrano, Dolores R; O'Connell, Peter; Paluch, Krzysztof J; Walsh, David; Healy, Anne Marie
• Is Part Of: Journal of pharmacy and pharmacology. Volume 68:Number 5(2016:May)
• Page Start: 665
• Page End: 677
• Publication Date: 2015-09-26
• Subjects: cocrystal habit -- dissolution -- flowability -- tabletability -- wettability; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12476
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: 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.