The effects of milling on the surface properties of form I paracetamol crystals.
OBJECTIVE
The effects of milling and particle size on surface energies of form I paracetamol crystals are reported.


METHODS
Paracetamol crystals (75-850 microm) were obtained by cooling methanol and acetone saturated solutions. Additionally, macroscopic (>2 cm) single crystals were grown by slow solvent evaporation from saturated solutions, ball milled and sieved into different particle size fractions. Surface properties were characterised using Inverse Gas Chromatography and compared with those calculated from sessile drop contact angle measurements on macroscopic single crystals.


RESULTS
Dispersive surface energies, gamma(d)SV for milled samples increased by 20% with decreasing particle size. With decreasing particle size acceptor numbers, KA values were constant but donor numbers, KB decreased. For unmilled materials KB was comparable to KA but with a significantly lower gamma(d)SV of only 33 mJ/m(2). Milling resulted in fracture along the crystal's lowest attachment energy plane (010), exposing facets of different surface chemistry to that of the native external facets theta for the (010) fracture plane confirmed a higher gamma(d)SV compared to external facets such as (011) of single crystals.


CONCLUSIONS
Milling exposes a hydrophobic surface for paracetamol form I crystals which becomes increasingly more dominant with decreasing particle size.
Heng
Jerry Y Y
JY
Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Thielmann
Frank
F
Williams
Daryl R
DR
D000082:Acetaminophen / Q000737:chemistry*; D000096:Acetone / Q000737:chemistry; D000465:Algorithms; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002849:Chromatography, Gas; D003460:Crystallization; D018360:Crystallography, X-Ray; D004339:Drug Compounding; D006863:Hydrogen-Ion Concentration; D000432:Methanol / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D010316:Particle Size; D013499:Surface Properties
D000096:Acetone; D000082:Acetaminophen; D000432:Methanol