Miscibility of nifedipine and hydrophilic polymers as measured by (1)H-NMR spin-lattice relaxation.
The miscibility of a drug with excipients in solid dispersions is considered to be one of the most important factors for preparation of stable amorphous solid dispersions. The purpose of the present study was to elucidate the feasibility of (1)H-NMR spin-lattice relaxation measurements to assess the miscibility of a drug with excipients. Solid dispersions of nifedipine with the hydrophilic polymers poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose (HPMC) and alpha,beta-poly(N-5-hydroxypentyl)-L-aspartamide (PHPA) with various weight ratios were prepared by spray drying, and the spin-lattice relaxation decay of the solid dispersions in a laboratory frame (T(1) decay) and in a rotating frame (T(1rho) decay) were measured. T(1rho) decay of nifedipine-PVP solid dispersions (3 : 7, 5 : 5 and 7 : 3) was describable with a mono-exponential equation, whereas T(1rho) decay of nifedipine-PHPA solid dispersions (3 : 7, 4 : 6 and 5 : 5) was describable with a bi-exponential equation. Because a mono-exponential T(1rho) decay indicates that the domain sizes of nifedipine and polymer in solid dispersion are less than several nm, it is speculated that nifedipine is miscible with PVP but not miscible with PHPA. All the nifedipine-PVP solid dispersions studied showed a single glass transition temperature (T(g)), whereas two glass transitions were observed for the nifedipine-PHPA solid dispersion (3 : 7), thus supporting the above speculation. For nifedipine-HPMC solid dispersions (3 : 7 and 5 : 5), the miscibility of nifedipine and HPMC could not be determined by DSC measurements due to the lack of obviously evident T(g). In contrast, (1)H-NMR spin-lattice relaxation measurements showed that nifedipine and HPMC are miscible, since T(1rho) decay of the solid dispersions (3 : 7, 5 : 5 and 7 : 3) was describable with a mono-exponential equation. These results indicate that (1)H-NMR spin-lattice relaxation measurements are useful for assessing the miscibility of a drug and an excipient in solid dispersions.
National Institute of Health Sciences, Tokyo, Japan. aso@nihs.go.jp
Yukio
Y
Aso
Sumie
S
Yoshioka
Tamaki
T
Miyazaki
Tohru
T
Kawanishi
Kazuyuki
K
Tanaka
Satoshi
S
Kitamura
Asako
A
Takakura
Takashi
T
Hayashi
Noriyuki
N
Muranushi
D002121:Calcium Channel Blockers / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D065347:Hypromellose Derivatives; D009682:Magnetic Resonance Spectroscopy; D008747:Methylcellulose / Q000031:analogs & derivatives; D009543:Nifedipine / Q000737:chemistry*; D010634:Phenobarbital / Q000737:chemistry; D011108:Polymers; D011205:Povidone / Q000737:chemistry; D012995:Solubility
D002121:Calcium Channel Blockers; D011108:Polymers; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D011205:Povidone; D009543:Nifedipine; D010634:Phenobarbital