title: Differences in crystallization rate of nitrendipine enantiomers in amorphous solid dispersions with HPMC and HPMCP.
abstract: To clarify the contribution of drug-polymer interaction to the physical stability of amorphous solid dispersions, we studied the crystallization rates of nitrendipine (NTR) enantiomers with identical physicochemical properties in the presence of hydroxypropylmethylcellulose (HPMC), hydroxypropylmethylcellulose phthalate (HPMCP) and polyvinylpyrrolidone (PVP). The overall crystallization rate at 60°C and the nucleation rate at 50-70°C of (+)-NTR were lower than those of (-)-NTR in the presence of 10-20% HPMC or HPMCP. In contrast, similar crystallization profiles were observed for the NTR enantiomers in solid dispersions containing PVP. The similar glass transition temperatures for solid dispersions of (-)-NTR and (+)-NTR suggested that the molecular mobility of the amorphous matrix did not differ between the enantiomers. These results indicate that the interaction between the NTR enantiomers and HPMC or HPMCP is stereoselective, and that differences in the stereoselective interaction create differences in physical stability between (-)-NTR and (+)-NTR at 50-70°C. However, no difference in physical stability between the enantiomers was obvious at 40°C. Loss of the difference in physical stability between the NTR enantiomers suggests that the stereoselective interaction between NTR and the polymers may not contribute significantly to the physical stabilization of amorphous NTR at 40°C.
authors.affiliation: Division of Drugs, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. miyazaki@nihs.go.jp
authors.forename: Tamaki
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Aso
authors.forename: Sumie
authors.initials: S
authors.lastname: Yoshioka
authors.forename: Toru
authors.initials: T
authors.lastname: Kawanishi
mesh_terms: D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D009568:Nitrendipine / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D013237:Stereoisomerism; D013696:Temperature; D044366:Transition Temperature
chemical_list: D002121:Calcium Channel Blockers; D005079:Excipients; D011108:Polymers; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate; D009568:Nitrendipine; D011205:Povidone