Formulation and evaluation of nimodipine-loaded lipid microspheres.
The purpose of this study was to develop an alternative, improved and better tolerated formulation and investigate the pharmacokinetic profile of the new formulation of nimodipine (NM) compared with nimodipine ethanol solutions. Lipid microspheres (LMs) prepared using lecithin and vegetable oils have attracted a lot of interest owing to their versatile properties, such as non-immunogenicity, being easily biodegradable and exhibiting high entrapment efficiency. NM incorporated in LMs could reduce irritation by avoiding the use of ethanol as a solubilizer. The solubility of NM was also increased by dissolving it in the oil phase. The particle size distribution, zeta potential, entrapment efficacy and assay of the NM-loaded LMs were found to be 188.2+/-5.4 nm, -31.6 mV, 94.2% and 1.04 mg mL(-1), respectively. The preparation was stable for 1 year at 4-10 degrees C. The formulation and some physicochemical properties of NM-loaded LMs were investigated. The pharmacokinetic and biodistribution studies were performed in rats at a dose of 1.2 mg kg(-1). From the observed data, there is no obvious retention of NM-loaded LMs in plasma. Moreover, incorporation of NM in LMs did not alter the tissue distribution significantly except for the relatively greater drug accumulation in the liver and spleen. The stimulation studies demonstrate that LMs of NM reduce irritation markedly compared with NM solutions. These results suggest that the LM system is a promising option to replace NM ethanol solutions as an intravenous treatment.
Yu
Jia
J
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
He
Hai Bing
HB
Tang
Xing
X
D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003102:Colloids / Q000737:chemistry; D004355:Drug Stability; D004423:Ear / Q000098:blood supply / Q000473:pathology; D000431:Ethanol / Q000737:chemistry; D007275:Injections, Intravenous; D008297:Male; D008863:Microspheres; D009553:Nimodipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010147:Pain Measurement / Q000379:methods; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010938:Plant Oils / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012965:Sodium Chloride / Q000737:chemistry; D012995:Solubility; D013154:Spleen / Q000737:chemistry / Q000187:drug effects; D014018:Tissue Distribution; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D014680:Veins / Q000187:drug effects / Q000473:pathology
D003102:Colloids; D010713:Phosphatidylcholines; D010938:Plant Oils; D014665:Vasodilator Agents; D000431:Ethanol; D012965:Sodium Chloride; D009553:Nimodipine