Evaluation of hypromellose acetate succinate (HPMCAS) as a carrier in solid dispersions.
The utility of hypromellose acetate succinate (HPMCAS), a cellulosic enteric coating agent, as a carrier in a solid dispersion of nifedipine (NP) was evaluated in comparison with other polymers, including hypromellose (HPMC), hypromellose phthalate (HPMCP), methacrylic acid ethyl acrylate copolymer (MAEA), and povidone (PVP). An X-ray diffraction study showed that the minimum amount of HPMCAS required to make the drug completely amorphous was the same as that of other cellulosic polymers, and less than that in dispersions using non-cellulosic polymers. Hypromellose acetate succinate showed the highest drug dissolution level from its solid dispersion in a dissolution study using a buffer of pH 6.8. This characteristic was unchanged after a storage test at high temperature and high humidity. The inhibitory effect of HPMCAS on recrystallization of NP from a supersaturated solution was the greatest among all the polymers examined. Further, the drug release pattern could be modulated by altering the ratio of succinoyl and acetyl moieties in the polymer chain. Our results indicate that HPMCAS is an attractive candidate for use as a carrier in solid dispersions.
Specialty Chemicals Research Center, Shin-Etsu Chemical Co., Ltd., Kubiki-mura, Nakakubiki-gun, Niigata, Japan. tanno_f@shinetsu.jp
Fumié
F
Tanno
Yuichi
Y
Nishiyama
Hiroyasu
H
Kokubo
Sakaé
S
Obara
D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry; D003460:Crystallization; D004337:Drug Carriers; D004355:Drug Stability; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D009543:Nifedipine / Q000008:administration & dosage / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D002121:Calcium Channel Blockers; D004337:Drug Carriers; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose; D009543:Nifedipine