title: Formulation of nimodipine nanocrystals for oral administration.
abstract: The aim of this paper is to optimize nimodipine (NMD) nanocrystals (NCs) for oral administration. The effects of independent process variables (microprecipitation temperature, shearing speed, shearing time, homogenization pressure and number of cycles) on the particle size have been studied. Experiments were conducted to optimize the formulation composition. A single factor exploration was used to screen the primary stabilizers. Then, the selected polymers/surfactants were further optimized using an L9 (3(4)) orthogonal design. The optimal formulation was composed of NMD (0.7 %, w/v), F127 (0.4 %, w/v), HPMC-E5 (0.1 %, w/v), and sodium deoxycholate (0.05 %, w/v) and was rod-shaped as shown by SEM observations, and it had a particle size of 833.3 ± 20.6 nm, determined by laser diffraction. These aqueous NCs were physically stable for 15 days. To further improve the stability, the NCs were freeze-dried. The powder obtained exhibited acceptable flowability and was physically stable for at least 24 months. Additionally, the NMD NCs displayed much higher dissolution profiles than the bulk drug. The pharmacokinetic results showed that the relative bioavailability was 397 % in comparison with Nimotop(®), suggesting that NCs are an efficient strategy for improving the oral bioavailability of poorly water-soluble drugs.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Mailbox 59#, No. 103, Wenhua Road, Shenyang, 110016, China.|GE Healthcare, No.1, HuaTuo Road, Zhangjiang Hi-tech Park, Shanghai, 210203, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Mailbox 59#, No. 103, Wenhua Road, Shenyang, 110016, China. graham_pharm@aliyun.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Mailbox 59#, No. 103, Wenhua Road, Shenyang, 110016, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Liaoning Institute for Drug Control, No.46, Guihe Street, Shenyang, 110023, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Mailbox 59#, No. 103, Wenhua Road, Shenyang, 110016, China. i_maple@163.com.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D036103:Nanotechnology; D009553:Nimodipine / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D010316:Particle Size; D011208:Powders; D011312:Pressure; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
chemical_list: D002121:Calcium Channel Blockers; D005079:Excipients; D011208:Powders; D013501:Surface-Active Agents; D009553:Nimodipine
keywords: Formulation; Nanocrystals; Nimodipine; Physical stability; Preparation