Molecular basis of crystal morphology-dependent adhesion behavior of mefenamic acid during tableting.
OBJECTIVE
The molecular basis of crystal surface adhesion leading to sticking was investigated by exploring the correlation of crystal adhesion to oxidized iron coated atomic force microscope (AFM) tips and bulk powder sticking behavior during tableting of two morphologically different crystals of a model drug, mefenamic acid (MA), to differences in their surface functional group orientation and energy.


METHODS
MA was recrystallized into two morphologies (plates and needles) of the same crystalline form. Crystal adhesion to oxidized iron coated AFM tips and bulk powder sticking to tablet punches was assessed using a direct compression formulation. Surface functional group orientation and energies on crystal faces were modeled using Accelrys Material Studio software.


RESULTS
Needle-shaped morphology showed higher sticking tendency than plates despite similar particle size. This correlated with higher crystal surface adhesion of needle-shaped morphology to oxidized iron coated AFM probe tips, and greater surface energy and exposure of polar functional groups.


CONCLUSIONS
Higher surface exposure of polar functional groups correlates with higher tendency to stick to metal surfaces and AFM tips, indicating involvement of specific polar interactions in the adhesion behavior. In addition, an AFM method is identified to prospectively assess the risk of sticking during the early stages of drug development.
Bristol-Myers Squibb, Co., One Squibb Dr., New Brunswick, New Jersey, 08901, USA.
Vrushali
V
Waknis
Elza
E
Chu
Roxana
R
Schlam
Alexander
A
Sidorenko
Sherif
S
Badawy
Shawn
S
Yin
Ajit S
AS
Narang
D000268:Adhesiveness; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods; D008528:Mefenamic Acid / Q000737:chemistry*; D018625:Microscopy, Atomic Force / Q000379:methods; D010316:Particle Size; D011208:Powders / Q000737:chemistry; D013499:Surface Properties; D013607:Tablets / Q000737:chemistry*
D011208:Powders; D013607:Tablets; D008528:Mefenamic Acid