title: Crystal morphology engineering of pharmaceutical solids: tabletting performance enhancement.
abstract: Crystal morphology engineering of a macrolide antibiotic, erythromycin A dihydrate, was investigated as a tool for tailoring tabletting performance of pharmaceutical solids. Crystal habit modification was induced by using a common pharmaceutical excipient, hydroxypropyl cellulose, as an additive during crystallization from solution. Observed morphology of the crystals was compared with the predicted Bravais-Friedel-Donnay-Harker morphology. An analysis of the molecular arrangements along the three dominant crystal faces [(002), (011), and (101)] was carried out using molecular simulation and thus the nature of the host-additive interactions was deduced. The crystals with modified habit showed improved compaction properties as compared with those of unmodified crystals. Overall, the results of this study proved that crystal morphology engineering is a valuable tool for enhancing tabletting properties of active pharmaceutical ingredients and thus of utmost practical value.
authors.affiliation: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. sabir.mirza@helsinki.fi
authors.forename: Sabiruddin
authors.initials: S
authors.lastname: Mirza
authors.forename: Inna
authors.initials: I
authors.lastname: Miroshnyk
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heinämäki
authors.forename: Osmo
authors.initials: O
authors.lastname: Antikainen
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Pia
authors.initials: P
authors.lastname: Vuorela
authors.forename: Heikki
authors.initials: H
authors.lastname: Vuorela
authors.forename: Jouko
authors.initials: J
authors.lastname: Yliruusi
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D003460:Crystallization; D004917:Erythromycin / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D013499:Surface Properties; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D005079:Excipients; D013607:Tablets; D004917:Erythromycin; D002482:Cellulose; C008079:hydroxypropylcellulose