Yao J, Hou L, Zhou J P, Zhang Z Q, Sun L
Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
Pharmazie. 2009 Oct;64(10):642-7.
The purpose of this study was to develop a microemulsion system for intranasal delivery of lorazepam. The phase behavior and properties of microemulsions were characterized in a pseudo-ternary system composed of Cremophor EL 35/Transcutol P/Lauroglycol FCC or Labrafil M 1944CS/water, and intranasal absorption of lorazepam from microemulsions was investigated in rabbit. The microemulsions, comprising of FCC, Cremophor EL 35/Transcutol P (1.5:1) and water, were optimal for intranasal delivery of lorazepam. These systems had a higher solubilization capacity with the particle size of <150 nm, and were stable at ambient conditions for at least six months. In vivo absorption studies showed that intranasal absorption of lorazepam from microemulsions at 0.38 mg/kg had the larger AUC(0-t), the longer half-life and the prolonged circulation time with the mean bioavailability of 80.84% for ME2 and 63.48% for ME8 as compared to the intramuscular injection at 0.16 mg/kg. These results indicate that microemulsions may bea promising approach for the intranasal delivery of lorazepam.
本研究的目的是开发一种用于鼻腔给药劳拉西泮的微乳剂系统。在由聚氧乙烯蓖麻油EL 35/二乙二醇单乙基醚/月桂二醇FCC或Labrafil M 1944CS/水组成的伪三元体系中表征了微乳剂的相行为和性质，并在兔体内研究了劳拉西泮从微乳剂中的鼻腔吸收情况。由FCC、聚氧乙烯蓖麻油EL 35/二乙二醇单乙基醚（1.5:1）和水组成的微乳剂对劳拉西泮的鼻腔给药最为适宜。这些体系具有较高的增溶能力，粒径<150 nm，在环境条件下至少稳定六个月。体内吸收研究表明，与0.16 mg/kg肌肉注射相比，0.38 mg/kg的微乳剂中劳拉西泮的鼻腔吸收具有更大的AUC(0-t)、更长的半衰期和延长的循环时间，ME2的平均生物利用度为80.84%，ME8为63.48%。这些结果表明，微乳剂可能是鼻腔给药劳拉西泮的一种有前景的方法。
