Optimization of the Dose of Penetration Enhancers in Celecoxib Gel by Factorial Design
ZENG Ming-hui1, XIONG Jing-yue2, ZHU Jiu-qun3, HUANG Juan1, HE Lin3, TAN Zheng-huai2*
1. Sichuan Qionglai Medical Center Hospital, Qionglai 611350, China; 2. Sichuan Provincial Academy of Traditional Chinese Medicine,Chengdu 610041, China; 3. Sichuan Provincial People's Hospital, Chengdu 610072, China
Abstract��OBJECTIVE To optimize the formula of celecoxib gel by studying the effects of different doses of penetration enhancers on the penetration of celecoxib through skin in vitro. METHODS With sodium alginate as the gel base, factorial design method was used to choose the optimal formula of penetration enhancers among four different formulas to prepare celecoxib gels. The release rate of celecoxib in the release media was detected by modified Franz diffusion cells method, and the steady percutaneous speed (J), permeability coefficient (Kp) and the accumulative permeation quantity (Q) in 12 h were calculated. RESULTS The accumulative permeation quantity (Q) in 12 h of celecoxib from the gels made with the four different formulas were 27.93,25.12,18.79 and 19.35 ��g��cm-2, respectively. The gel with 1% azone and 1% menthol as penetration enhancers had the maximum Q value, 27.93 ��g��cm-2, its penetration process conformed to Higuchi equation, and the steady percutaneous speed (J) and permeability coefficient(Kp)were also higher than the other three experimental groups. CONCLUSION With sodium alginate as the gel base, azone and menthol have a synergistic effect on the percutaneous penetration of celecoxib gels, and the best formula is 1% azone and 1% menthol.
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ZENG Ming-hui, XIONG Jing-yue, ZHU Jiu-qun, HUANG Juan, HE Lin, TAN Zheng-huai. Optimization of the Dose of Penetration Enhancers in Celecoxib Gel by Factorial Design. Chinese Pharmaceutical Journal, 2017, 52(4): 293-297.
FENG F Y. Specific inhibitor of cyclo-oxygenase-2��celecoxib [J]. Guangzhou Med Pharm(����ҽҩ), 2001, 32(4):1-2.
[2]
FU Y, CHENG G Q, LIU H T. Evaluate the therapeutical effect on the acute renal colic [J]. Heilongjiang Med Pharm(������ҽҩ��ѧ),2008, 31(5):47-48.
[3]
XU H M, XU X. Analyze the prescription with celecoxib used in outpatient department of general hospital [J]. Chin Pharm J(�й�ҩѧ��־), 2009,44(20):1596-1598.
[4]
ZHAO Q X, SUN Y Q, WEN B F, et al. The research progress of gel [J]. Shandong Chem Ind(ɽ������),2015, 44(7):53-56.
[5]
QI H Y, LI L, WU C J. Advanced resrarch on penetration inhacing effect of menthol [J]. Lishizhen Med Mater Med Res(ʱ���ҽ��ҩ), 2006, 17(9):1776-1778.
[6]
YU K L, SUN J H. Study on the mechanism of some kinds of penetration enhancers [J]. Shandong Med Pharm(ɽ��ҽҩ), 2007, 47(11):30-31.
[7]
LIN H. Azone facilitate the 14 kinds of drugs transdermal absorption [J]. Tianjin Pharm(���ҩѧ), 1997, 9(3):25-28.
[8]
WANG H, CHEN L, ZHANG R T, et al. The evaluation of mentholon cutaneous safety [J]. Pharmacol Clin Chin Mater Med(��ҩҩ�����ٴ�),2008,24(3):32-35.
[9]
YU B T, FAN K H, JIN W H, et al. Effects of different contents of azone on transdermal absorption of manidipine cream in vitro [J]. Med J Southwest Nat Defending(���Ϲ���ҽҩ), 2011,3:250-252.
[10]
YANG T Y, YI Y M. The effect of mixed transdermal enhancers on percutaneous absorption of asprin gel [J]. Acta Univ Med Tongji(ͬ��ҽ�ƴ�ѧѧ��), 2001,6:533-534.
[11]
ZHOU X F, WU C P, SUN H H.Preparation of celecoxib liposomal gels and its transdermal permeation kinetics in vitro [J]. Chin J New Drugs Clin Rem(�й���ҩ���ٴ���־), 2007, 47(11):30-31.
[12]
WANG J Y, LA Y, LIN H M, et al. Effect of menthol on transdermal absorption of chinese herbal medicinal ingredients with different logP values [J]. Chin J New Drugs (�й���ҩ��־), 2016, 25(2):202-209.
[13]
ZENG M H, TAN Z H,HE L, et al. Study on the effect of azone in percutaneous absorption of spironolactone [J]. Tianjin Pharm(���ҩѧ), 2003, 15(4):3-5.
[14]
SUN A Z, ZHENG Y,WANG Y J, et al. Perparation of mangiferin-loaded transfersomes and its transdermal dilivery characterstics[J]. Chin Pharm J(�й�ҩѧ��־),2016, 51(9):727-731.
[15]
LI Y F, DENG Y J, LIU S Q, et al. Progresses of transdermal preparation research [J]. Chin Pharm J(�й�ҩѧ��־), 1997, 32(1):3-7.
[16]
ADRIAN C W, BRIAN W B. Penetration enhancers [J]. Adv Drug Deliv Rev, 2012, 64:128-137.
[17]
WANG Y Z, DU S Y, HUI J G. Election of proper animal skin for the percutaneous endosmosis of lappaconitine gel [J]. China J Chin Med(��ҽѧ��), 2011,26(11):1344-1345.
[18]
XIA L H, QIU Q D. Effect of azone and menthol on the in vitro pereutangeous permeability of the compound asiaiteoside gel [J]. Chin J Hosp Pharm(�й�ҽԺҩѧ��־), 2010, 30(18):1538-1541.
2017, Vol. 52 
