Cryomilling-induced solid dispersion of poor glass forming/poorly water-soluble mefenamic acid with polyvinylpyrrolidone K12.
The effect of mechanical impact on the polymorphic transformation of mefenamic acid (MFA) and the formation of a solid dispersion of mefenamic acid, a poor glass forming/poorly-water soluble compound, with polyvinylpyrrolidone (PVP) K12 was investigated. The implication of solid dispersion formation on solubility enhancement of MFA, prepared by cryomilling, was investigated. Solid state characterization was conducted using powder X-ray diffraction (PXRD) and Fourier-transform infrared (FTIR) spectroscopy combined with crystal structure analysis. Apparent solubility of the mixtures in pH 7.4 buffer was measured. A calculation to compare the powder patterns and FTIR spectra of solid dispersions with the corresponding physical mixtures was conducted. Solid state characterization showed that (1) MFA I transformed to MFA II when pure MFA I was cryogenically milled (CM); and (2) MFA forms a solid dispersion when MFA was cryogenically milled with PVP K12. FTIR spectral analysis showed that hydrogen bonding facilitated by mechanical impact played a major role in forming solid dispersions. The apparent solubility of MFA was significantly improved by making a solid dispersion with PVP K12 via cryomilling. This study highlights the importance of cryomilling with a good hydrogen bond forming excipient as a technique to prepare solid dispersion, especially when a compound shows a poor glass forming ability and therefore, is not easy to form amorphous forms by conventional method.
College of Pharmacy, Korea University , Sejong , Korea and.
Naewon
N
Kang
Jangmi
J
Lee
Ji Na
JN
Choi
Chen
C
Mao
Eun Hee
EH
Lee
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D006860:Hydrogen Bonding; D008528:Mefenamic Acid / Q000008:administration & dosage* / Q000737:chemistry; D011205:Povidone / Q000737:chemistry*; D011208:Powders; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000008:administration & dosage; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D011208:Powders; D014867:Water; D008528:Mefenamic Acid; D011205:Povidone
Ball-milling; PVP K12; cryomilling; mefenamic acid; solid dispersion