Solid-state nuclear magnetic resonance determination of the physical form of BHA on common pharmaceutical excipients.
OBJECTIVE
The purpose of this study was to evaluate the physical form of 2-tert-butyl-4-methoxy-phenol (BHA) following wet granulation onto common pharmaceutical excipients.


METHODS
A 13C label was incorporated into the methoxy group of BHA, the major isomer in synthetic butylated hydroxyanisole. Solutions of the labeled BHA were used to load the labeled BHA onto common pharmaceutical excipients. After air drying under ambient conditions, the mixtures were examined by 13C MAS and CP/MAS nuclear magnetic resonance (NMR) spectroscopy to evaluate the physical form of the BHA.


RESULTS
The data suggested that BHA could exist as either a crystalline or an amorphous component and that amorphous material was either bound to excipients or relatively mobile during the time of the NMR experiment. At 0.1% loading, BHA appeared to be amorphous and mobile in the freshly prepared blends. At 0.5% loading, BHA was shown to be amorphous on microcrystalline cellulose (MCC) and hydroxypropylmethylcellulose (HPMC) while remaining crystalline on lactose, mannitol, calcium phosphate dihydrate, and croscarmellose sodium.


CONCLUSIONS
Solid-state NMR spectroscopy has been used to probe the physical forms of 13C-labeled BHA granulated onto common pharmaceutical excipients. The techniques described in this paper may be applied to help explain stability changes in formulations containing BHA.
Remenar
Julius F
JF
Transfer Pharmaceuticals, Lexington, Massachusetts 02421, USA.
Wenslow
Robert
R
Ostovic
Drazen
D
Peresypkin
Andrey
A
D002083:Butylated Hydroxyanisole / Q000737:chemistry*; D003460:Crystallization; D005079:Excipients / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D044367:Phase Transition
D005079:Excipients; D002083:Butylated Hydroxyanisole