摘要
目的 研究外消旋体酮洛芬（rac-Ket）在酸性释放介质中的立体选择性释放行为。 方法 以专属性的手性HPLC考察酮洛芬可注射植入剂在 pH 2.5释放介质中的对映体选择性释放行为。 结果 体外释放实验结果表明，以可生物降解的乳酸-乙醇酸共聚物（D，L-PLG）为载体制成的外消旋体酮洛芬可注射植入剂，在pH 2.5的酸性释放介质中可维持约2.5月的缓慢释放。从立体选择性的角度观察，S-(+)-Ket的释放略快于R-（-）-Ket，S/R-Ket的比值在1.01~1.03之间，但经独立样本的t检验，认为这种差异没有显著性(P>0.05)。这与我们过去以pH 7.4为介质的对映体释放结果不同，显示载体D，L-PLG在不同pH条件下的降解方式可能影响对映体的释放行为。结论 与在pH 7.4释放介质中的研究结果不同，7%rac-Ket可注射植入剂在酸性条件下（pH 2.5）的对映体释放缺少选择性。
Abstract
OBJECTIVE To investigate the stereoselective release from racemic ketoprofen injectable implants in pH 2.5 release medium. METHODS The enantioselective release at pH 2.5 was evaluated by a reversed-phase HPLC analytical method. S-(+) and R-（-） enantiomers of ketoprofen were determined simultaneously in release samples. RESULTS In vitro release study showed that racemic ketoprofen implants obtained sustained release of the drug lasting about 2.5 months in a pH 2.5 release medium. Moreover， S-(+)-Ket released faster than R-（-）-Ket in the implants containing 7% of rac-Ket and the ratio of S- to R-enantiomer ranged from 1.01 to 1.03. However， there was no significant difference between two enantiomers. CONCLUSION Difference of stereoselective release between the acidic and the neutral release medium maybe relate to the various biodegradable PLG. Compared with the significant release difference between two enantiomers in vitro at pH 7.4， the release of two enantiomers from rac-Ket injectable implants at pH 2.5 showed no stereoselectivity.
关键词
立体选择性释放 /
酮洛芬对映体 /
乳酸-乙醇酸共聚物 /
可注射植入剂 /
反相高效液相色谱法 /
酸性释放介质
{{custom_keyword}} /
Key words
stereoselective release /
enantiomer ketoprofen /
D /
L-PLG /
biodegradable injectable implants /
RP-HPLC /
acidic release medium
{{custom_keyword}} /
谢方 王胜浩.
酮洛芬可注射植入剂在酸性介质中的立体选择性释放行为[J]. 中国药学杂志, 2010, 45(3): 199-202
XIE Fng;WNG Sheng-ho.
Stereoselective Release from Racemic Ketoprofen Injectable Implants in pH 2.5 Medium[J]. Chinese Pharmaceutical Journal, 2010, 45(3): 199-202
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
［1］ WANG S H， ZENG S. Stereorelease of enantiomers from chiral formulation［J］.Chin Pharm J (中国药学杂志)，2005，40（1）：10-12.
［2］ DUDDU S P， VAKILYNEJAD M， JAMALI F. Stereoselective dissolution of propranolol hydrochloride from hydroxypropylmethylcellulose matrices［J］.Pharm Res，1993，10（11）：1648-1653.
［3］ ALVAREZ C， TORRADO J J， CADORNIGA R. Stereoselective drug release from ketoprofen and ricobendazole matrix tablets［J］. Chirality，1999，11（8）：611-615.
［4］ FOLRENC A T， ATTWOOD D. Physicochemical Principles of Pharmacy［M］. London： MacMillan，Ltd.， 1981.
［5］ VAKILY M， JAMALI F. Human pharmacokinetics of tiaprofenic acid after regular and sustained release formulations：lack of chiral inversion and stereoselective release［J］.J Pharm Sci，1994，83（4）：495-498.
［6］ VAKILY M， JAMALI F. Inclusion complexation of heptakis(2，6-di-ethyl)- β-cyclodextrin with tiaprofenic acid：pharmacokinetic consequences of a pH-dependent release and stereoselective dissolution［J］.J Pharm Sci， 1995， 84（6）：1014-1019.
［7］ SOLINIS M A， CRUZ Y， HERNANDEZ R M， et al. Release of ketoprofen enantiomers from HPMC K100M matrices--diffusion studies［J］.Int J Pharm， 2002，239（1-2）：61-68.
［8］ WANG S H， LIANG Z H， ZENG S. Monitoring release of ketoprofen enantiomers from biodegradable Poly(D， L-lactide-co-glycolide) Injectable Implants［J］.Int J Pharm， 2007，337(1-2)：102-108.
［9］ ARMSTRONG D W， TANG Y B， CHEN S S. Macrocylic antiobiotics as a new class of chiral selectors for liquid chromatography［J］.Anal Chem， 1994，66（9）：1473-1478.
［10］ PHEOURCQ F， JARRY C， BANNWARTH B. Chiral resolution of flurbiprofen and ketoprofen enantiomers by HPLC on a glycopeptide-type column chiral stationary phase［J］.Biomed Chromatogr， 2001，15（3）：217-222.
［11］ WANG S H， ZHANG L C， ZENG S， et al. Controlled release of levonorgestrel from biodegradable Poly(D，L-lactide-co-glycolide) Microspheres： in vitro and in vivo studies［J］.Int J Pharm， 2005, 301(1-2)：217-225.
［12］ SHAH N H， RAILKAR A S， CHEN F C， et al. A biodegradable injectable implant for delivering micro and macromolecules using poly(lactic-co-glycolic acid) (PLGA)copolymer［J］.J Controlled Release， 1993，27(2)：139-147.
［13］ ELIAZ R E， WALLACH D， KOST J. Delivery of soluble tumor necrosis factor receptor from in-situ forming PLGA implants：in vivo［J］.Pharm Res， 2000，17(12)：1546-1550.
［14］ PARK T G. Degradation of poly(lactic-co-glycolic acid) microspheres：effect of copolymer composition ［J］.Biomaterials，1995，16(15)：1123-1130.
［15］ CHEN C C， CHUEH J Y， TSENG H， et al. Preparation and characterization of biodegradable PLA polymeric blends［J］. Biomaterials， 2003，24(17)：1167-1173.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(1029 KB)
