pH对盐酸美普他酚鼻腔吸收的影响(英文)

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Journal of Chinese Pharmaceutical Sciences 2004 , 1Environment on Nasal Absorption of Meptazinol Hydrochloride
SHI Zhen2qi and J IANG Xin2guo
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217 )
[2 ]
, meptazinol hydrochloride , an analgesic. More2
over , the evaluation in the past of the effect of properties of drugs on the transport from nasal cavity to CSF was generally based on the experimental skill by which it was impossible to obtainΠ continuous CSF samples from the same animal , such as rats. The disadvantage lied in the individual difference of rats as well as the difficulty in in2 vestigating this effect only based on the comparison of the CSF concentrations at a single time point . Thus , we per2 formed in vivo experiment using an improved method of cisternal puncture to sample CSF continuously from the same rat to study this effect .
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© 1995-2004 Tsinghua Tongfang Optical Disc Co., Ltd. All rights reserved.
Journal of Chinese Pharmaceutical Sciences 2004 , 13(1)
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of MEP were achieved by dissolving the drug into the buffer solution with different pH because it is very soluble in water. The concentration of perfused solution and nasal formulation was 210 mg・ mL tively. Animals The animal experiment was carried out in compliance with the protocol of Animal Use and Care by Medical Cen2 ter of Fudan University. Male Sprague2Dawley ( 300 - 400 g) rats were housed with free access to food and water within 24 h before experiments.
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and 80 mg・ mL
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, respec2
for at least 100 μ L plasma. Meanwhile 40
Rats were anesthetized with an intraperitoneal dose - 1 of 20 % ( WΠ V) urethane ( 112 g・ kg ) and kept under anesthesia throughout the whole experiment . According to the previous method , the trachea was cannulated and a polyethylene ( PE) tube was inserted through esophagus into the posterior part of the nasal cavity with the oral cav2 ity blocked by the mucilage. The nasal cavity was per2 fused with a series of drug2contained phosphate buffer (pH 415 , 515 , 615 , 715 , 815 ) in a single circulation system in which the temperature was maintained at 37 ℃ by a water bath and the flow rate was adjusted to 215 mL ・ - 1 min by a peristaltic pump (DHL2A , Shanghai Huxi An2 alytical Instrument Factory , Shanghai , China) . A sample of 10 μ L of the perfused solution was collected by mi2 crosyringe at 0 , 15 , 30 , 45 , and 60 min , then diluted and measured by HPLC.
Introduction
Recently , nasal drug delivery system ( NDDS) has been paid more and more attention. Furthermore , the course of efficiently delivering drugs or compounds to cen2 tral nervous system ( CNS ) by NDDS has become the highlight of research. It is known that absorption across biological membrane is related to the pH environment in formulation. And it was also reported that both the trans2 port of sulphisomidine , a hydrophilic drug , from nasal cavity to cerebrospinal fluid ( CSF) and the nasal absorp2 tion were dependent on the dissociation of the compou2 nd
. It is found that highly lipophilic compounds will lead
Materials and Methods
Materials Meptazinol hydrochloride ( MEP ) was supplied by Department of Medicinal Chemistry , School of Pharmacy , Fudan Universiy ( Shanghai , China) . Urethane ( Shanghai Chemical Reagents Corp . , China) was used as anesthetic for animal experiments. Millipore ultrapure deionized wa2 ter ( Millipore Simpli Laboratory , USA ) was used for preparation of the solutions for perfused solution and buff2 er of HPLC mobile phase. HPLC grade methanol was pur2 chased from Shanghai Chemical Reagents Research Insti2 tute , China. All other chemicals were of commercially analytical grade. MEP formulations Formulations for perfusion and nasal administration
Received date : 2003210212.
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Foundation item : National Natural Science Foundation of China (30171112) Corresponding author : Tel 0212542327381 , Fax 021254237381 , E2mail : xgjiang @shmu. edu. cn
In situ perfusion experiment
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When cisternal puncture experiment was completed , a PE210 tube connected with a microsyringe was inserted into right nostril of the rat to administer the nasal formula2 tion at a dose of 100 μ L・ kg . CSF and blood sample were collected at the predetermined time intervals ( 5 , 15 , 30 , 45 , 60 , 90 , 120 , 180 min ) . The 0125 mL blood of was taken from the tail vein and placed into a he2 parinized PE conical tubes , then centrifuged for 10 min at 3000 r・ min