title: Can crystal engineering be as beneficial as micronisation and overcome its pitfalls?: A case study with cilostazol.
abstract: Improvement in dissolution of the drugs having poor solubility is a challenge in pharmaceutical industry. Micronization is one technique, employed for dissolution enhancement of cilostazol, a BCS class II drug. However, the obtained micronized drug possesses poor flowability. The aim of this study was to improve the dissolution rate and flow properties of cilostazol by crystal engineering, using habit modification method and compare with micronized cilostazol bulk drug. Simulation studies were performed to predict the effect of solvents on cilostazol crystal habit. Cilostazol crystals with different habits were prepared by solvent:anti-solvent crystallization technique. SEM, FTIR, DSC, TGA and PXRD were used for solid state characterization. The results revealed that cilostazol re-crystallized from methanol-hexane system were hexagonal and ethanol-hexane system gave rods. Cilostazol engineered habits showed increased dissolution rate than unprocessed drug but similar dissolution rate when compared to micronized cilostazol. Micronized cilostazol showed a dissolution efficiency of 75.58% where as cilostazol recrystallized from methanol-hexane and ethanol-hexane systems resulted in a dissolution efficiency of 72.63% and 68.63%, respectively. In addition, crystal engineering resulted in improved flow properties of re-crystallized habits when compared to micronized form of the drug. In conclusion, crystal engineering by habit modification show potential for dissolution enhancement with an added advantage of improved flow properties over micronization technique, for poorly soluble drugs like cilostazol.
authors.affiliation: National Institute of Pharmaceutical Education & Research, Hyderabad, India.
authors.forename: Kodukula
authors.initials: K
authors.lastname: Sai Gouthami
authors.affiliation: National Institute of Pharmaceutical Education & Research, Hyderabad, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.affiliation: National Institute of Pharmaceutical Education & Research, Hyderabad, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Thipparaboina
authors.affiliation: National Institute of Pharmaceutical Education & Research, Hyderabad, India.
authors.forename: Rahul B
authors.initials: RB
authors.lastname: Chavan
authors.affiliation: National Institute of Pharmaceutical Education & Research, Hyderabad, India. Electronic address: nalini@niperhyd.ac.in.
authors.forename: Nalini R
authors.initials: NR
authors.lastname: Shastri
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077407:Cilostazol; D003460:Crystallization / Q000379:methods*; D000431:Ethanol / Q000737:chemistry; D006586:Hexanes / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D008855:Microscopy, Electron, Scanning / Q000379:methods; D033362:Powder Diffraction / Q000379:methods; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D013777:Tetrazoles / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D006586:Hexanes; D012997:Solvents; D013777:Tetrazoles; D000431:Ethanol; D000077407:Cilostazol; D000432:Methanol
keywords: Cilostazol; Crystal habit modification; Dissolution; Flow properties; Micronisation