Formulation of nimodipine nanocrystals for oral administration
- 392 Downloads
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 (34) 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.
KeywordsNimodipine Nanocrystals Preparation Formulation Physical stability
This work was financially supported by Doctoral Research Funding of Liaoning Province (No. 20141066), by the General Project in Education Department of Liaoning Province (No. L2014379), by the Career Development Program for Young Teachers in Shenyang Pharmaceutical University, by the National Nature Science Foundation of China (No. 81502993).
Compliance with Ethical standards
Conflict of Interest
No potential conflicts of interest were disclosed by any of the authors.
- Elsayed I, Abdelbary AA, Elshafeey AH (2014) Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers. Int J Nanomed 9:2943–2953Google Scholar
- Kipp J, Joseph CT, Doty MJ, Rebbeck CL (2005) Microprecipitation method for preparing submicron suspensions. U.S. Patent 6,869,617Google Scholar
- Li Y, Sun S, Chang Q, Zhang L, Wang G, Chen W, Miao X, Zheng Y (2013) A strategy for the improvement of the bioavailability and antiosteoporosis activity of BCS IV flavonoid glycosides through the formulation of their lipophilic aglycone into nanocrystals. Mol Pharm 10:2534–2542CrossRefPubMedGoogle Scholar
- Petersen R (2010) Nanocrystals for use in topical cosmetic formulations and method of production thereof. U.S. Patent 20,100,047,297 (A1)Google Scholar
- Pickard JD, Murray GD, Illingworth R, Shaw MD, Teasdale GM, Foy PM, Humphrey PR, Lang DA, Nelson R, Richards P (1989) Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 298:636–642PubMedCentralCrossRefPubMedGoogle Scholar
- Yue PF, Li Y, Wan J, Wang Y, Yang M, Zhu WF, Wang CH, Yuan HL (2013) Process optimization and evaluation of novel baicalin solid nanocrystals. Int J Pharm 8:2961–2973Google Scholar