Asian Journal of Pharmaceutics
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RESEARCH ARTICLE Table of Contents   
Year : 2008  |  Volume : 2  |  Issue : 1  |  Page : 35-37
Effect of enhancers on permeation kinetics of captopril for transdermal system


1 K.L.E. Society's College of Pharmacy, II block, Rajajinagar, Bangalore - 560 010, India
2 Department of Pharmacology, Annamalai University, Chidambaram, Tamilnadu, India

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   Abstract 

Transdermal drug delivery system has seen a veritable explosion in the past decades. In the present scenario, very few transdermal patches are commercially available. The captopril being an antihypertensive drug requires chronic administration. Since the drug has an extensive first-pass metabolism, an attempt was made to develop transdermal drug delivery system for better patient compliance. In this study, flux and permeation enhancement trials of captopril were carried out using modified Franz diffusion cells through siloxane membrane for 8 h. Citral and dimethyl formamide as permeation enhancers showed the best permeability as compared to sodium tauroglycholate, sodium lauryl sulfate, etc. One longstanding approach for improving transdermal drug delivery uses penetration enhancers (also called sorption promoters or accelerants), which penetrate into skin to reversibly decrease the barrier resistance.

Keywords: Captopril, transdermal permeation studies

How to cite this article:
Desai B G, Annamalai A R, Divya B, Dinesh B M. Effect of enhancers on permeation kinetics of captopril for transdermal system. Asian J Pharm 2008;2:35-7

How to cite this URL:
Desai B G, Annamalai A R, Divya B, Dinesh B M. Effect of enhancers on permeation kinetics of captopril for transdermal system. Asian J Pharm [serial online] 2008 [cited 2014 Oct 31];2:35-7. Available from: http://www.asiapharmaceutics.info/text.asp?2008/2/1/35/41563



   Introduction Top


The principle of transdermal drug delivery systems is to deliver drug across epidermis to achieve systemic effect over a prolonged period of time. Because of these attributes, transdermal drug delivery systems offer many advantages such as reduced side effects, improved patient compliance, elimination of first-pass metabolism, and sustained drug delivery. [ 1]

Captopril is classified as an antihypertensive. It has mean plasma half-life of 2 to 3 h, and only 40% of the orally administered drug reaches the circulation due to hepatic metabolism. The present research was directed to examine the release rate of captopril and see the enhancer effect on the flux and enhancement ratio. This study was aimed at developing a suitable film formulation containing captopril for transdermal use; the embedded drug should be released without any preferential binding to the polymer. [ 2],[3]

There has been a giant leap by the pharmaceutical industry with respect to innovations in the new drug delivery arena in the past two decades. These innovations and changes in strategy present newer challenges and brighter opportunities for the application of new methodologies in the drug delivery process. Drug delivery through intact skin is of utmost importance for controlled release of drugs for their extended and safe use, which is yet to be successfully accomplished for a large number of drugs. Formulations on skin can be classified into two categories according to the target site of action of the containing drugs. One has systemic action after drug uptake from the cutaneous microvascular network, and the other exhibits local effects in the skin. The current study focuses the drug release kinetics from the rate-limiting membrane by varying the type of solvent used, polymeric films, and drug loading in transdermal delivery systems.


   Materials and Methods Top


Captopril was a gift sample from Micro Labs, Bangalore; dimethyl sulfoxide, sodium lauryl sulfate, dimethyl fluride, citric acid sodium taurocholate, eugenol were obtained from S.D. Fine Chemicals, Mumbai. All the solvents and other reagents were of analytical or pharmacopoeial grade.

Solubility measurement

The solubility of captopril was determined at several values of pH, viz., 6.2, 7.0, 7.4, and 8.0; excess of captopril was added to 5 mL of phosphate buffer solutions to form saturated solution. This solution was left for 24 h at 37C. The suspensions were filtered using a 0.45 #. The concentration of captopril was determined spectrophotometrically by measuring at 205 nm. [ 4],[5],[6]

Partition coefficient of drug in octanol/water

The partition coefficient of the drug was determined by taking equal volumes of 1-octanol and aqueous solution in a separating funnel. Ten milligrams of drug was dissolved in 10 mL buffer solutions of pH 6.2, 7, 7.4, and 8.0 separately, to which 10 mL of octanol was added and kept in a separating funnel for 24 h. The aqueous layer was collected, and concentration of captopril was measured spectrophotometrically at 205 nm using buffer of the respective pH as blank. [ 7]

Permeability study

The siloxane membrane was washed under running water for 3 to 4 h in order to remove glycerol, which is induced as a humectant. Removal of sulfur compounds can be accomplished by treating the siloxane membrane with a 0.3% w/v solution of sodium sulfide at 80C for 1 min and washing with hot water (60C) for 2 min, followed by acidification with a 0.2% v/v solution of sulfuric acid and then rinsing with hot water to remove the acid. This siloxane membrane will retain most proteins of molecular weight 12,000 or greater.

The drug solution was prepared as per the dose. Fifteen milligrams of drug per 2 mL of buffer (7.4 pH) was taken in the donor compartment. The siloxane membrane was mounted in the space between the donor and the receptor compartments. The receptor cell contained phosphate buffer of pH 7.4 as the medium. The samples were withdrawn every hour. The medium was magnetically stirred for uniform drug distribution and was maintained at a temperature of 37C 1C. The amount of drug diffused was estimated spectrophotometrically at 205 nm. The release details are given under 'RESULTS.'

The enhancers considered for the study were sodium lauryl sulfate (SLS), dimethyl sulfoxide (DMSO), dimethyl formamide (DMF), hyaluronidase and sodium tauroglycholate (STG), citral, citric acid, and eugenol. The donor compartment contained a suspension of the drug and 1% w/w concentration of different enhancers. Siloxane membrane was used as the barrier. All other experimental conditions and analytical techniques followed were similar to those reported in permeability study section. [8],[9],[10],[11],[12],[13],[14],[15],[16],[17]


   Results and Discussion Top


Effect of pH on solubility

The values of solubility of captopril at different values of pH of phosphate buffer solution were determined, and they were found to be 8.764, 17.580, 24.219, and 30.198 mg/mL in 6.2-, 7-, 7.4-, and 8.0-pH buffers respectively. As the pH of the buffer increased, the solubility of captopril was also found to increase.

Effect of pH on partition coefficient

The partition coefficient of captopril was determined in phosphate buffers of pH 6.2, 7.0, 7.4, and 8.0, and the partition coefficients were found to be 1.0452, 1.418, 3.859, and 1.414 respectively.

Permeation studies

The permeation studies were carried out using a passive diffusion cell, and the membrane used was siloxane membrane [Figure 1]. The permeability coefficient and flux of captopril were found to be 4.35 cm/h and 65.31 g/cm 2 /h respectively.

The enhancement ratio of the drug with different enhancers was studied using passive diffusion cell through dialysis membrane. The permeability coefficient, flux, and enhancement ratio of captopril [Figure 2] [Table 1] with dimethyl sulfoxide (1% DMSO) were found to be 13.80 cm/h, 207.14 g/cm 2 /h, and 3.172% respectively. The permeability coefficient, flux, and enhancement ratio of captopril with sodium lauryl sulfate (1% SLS) were found to be 5.09 cm/h, 76.43 g/cm 2 /h, and 1.170% respectively. The permeability coefficient, flux, and enhancement ratio of captopril with dimethyl fluride (1% DMF) were found to be 5.377 cm/h, 80.66 g/cm 2 /h, and 1.236% respectively. The permeability coefficient, flux, and enhancement ratio of captopril with sodium tauroglycholate (1% STG) were found to be 7.06 cm/h, 105.9 g/cm 2 /h, and 1.622% respectively. The permeability coefficient, flux, and enhancement ratio of captopril with citric acid (1%) were found to be 9.67 cm/h, 145.15 g/cm 2 /h, and 2.22% respectively. The permeability coefficient, flux, and enhancement ratio of captopril with citral (1%) were found to be 11.07 cm/h, 166.05 g/cm 2 /h, and 2.544% respectively.

 
   References Top

1.Hadgraft J, Lane ME. Skin permeation: The years of enlightenment. Int J Pharm 2005;305:2-12.  Back to cited text no. 1    
2.Bruton LL, Laza JS, Parker KL. Goodman Gilman's: The pharmacological basis of therapeutics. New York: McGraw Hill Medical Publishing Division; 2006. p. 801-10.  Back to cited text no. 2    
3.Martindale: The complete drug reference. The enhancement effect of surfactants on the penetration of lorazepam through rat skin. 33 rd ed. London: Pharmaceutical Press; 2007. p. 853-4.  Back to cited text no. 3    
4.Nokhodchi A, Shokri J, Dashbolaghi A, Hassan-Zadeh D, Ghafourian T, Barzegar-Jalali M. The enhancement effect of surfactants on the penetration of lorazepam through rat skin. Int J Pharm 2003;250:359-69.  Back to cited text no. 4    
5.Sutariya V, Mashru R, Sunkalia MS. Transbuccal delivery of lomotrigine across procine buccal mucosa in vitro determination of roots of buccal transport. J Pharm Sci., 2005;8:54-62.  Back to cited text no. 5    
6.Mashru R, Sutariya V, Sankalia M, Sankalia J. Transbuccal delivery of lamotrigine across porcine buccal mucosa: In vitro determination of routes of buccal transport. J Pharm Pharma Sci 2005;8:54-62.  Back to cited text no. 6    
7.Shah JC, Ross JS. Reduction in skin permeation of n,n-diethyl-m-toluamide by altering the skin/vehicle partition co-efficient. J Control Release 2000;67:211-21.  Back to cited text no. 7    
8.Pugh WJ, Hadgraft J. Prediction of human skin permeability coefficients. Int J Pharm 1994;103:163-78.  Back to cited text no. 8    
9.Hadgraft J, Lane ME. Skin permeation: The years of enlightenment. Int J Pharm 2005;305:2-12.  Back to cited text no. 9    
10.Nanayakkara GR, Bartlett A, Forbes B, Marriott C, Whitfield PJ, Brown MB. The effect of unsaturated fatty acids in benzyl alcohol on the percutaneous permeation of three model penetrants. Int J Pharm 2005;301:129-39.  Back to cited text no. 10    
11.Ghafourian T, Zandasrar P, Hamishekar H, Nokhodchi A. The effect of penetration enhancers on drug delivery through skin: A QSAR study. J Control Release 2004;99:113-25.  Back to cited text no. 11    
12.Hadgraft J. Skin deep. Eur J Pharm Biol 2004;58:291-9.  Back to cited text no. 12    
13.Kanikkannan N, Singh M. Skin permeation enhancement effect and skin irritation of saturated fatty alcohols. Int J Pharm 2002;248:219-28.  Back to cited text no. 13    
14.Akimoto T, Kawahara K, Nagase Y, Aoyagi T. Polymeric transdermal drug penetration enhancer: The enhancing effect of oligodimethylsiloxane containing a glucopyranosyl end group. J Control Release 2001;77:49-57.  Back to cited text no. 14    
15.Copovν O, Dνez-Sales JV, Herrαez-Domνnguez, Herrαez-Domνnguez M. Enhancing effect of alpha-hydroxyacids on " in vitro" permeation across the human skin of compounds with different lipophilicity. Int J Pharm 2006;314:31-6.  Back to cited text no. 15    
16.Nokhodchi A, Shokri J, Dashbolaghi A, Hassan-Zadeh D, Ghafourian T, Barzegar-Jalali M. The enhancement effect of surfactants on the penetration of lorazepam through rat skin. Int J Pharm 2003;250:359-69.  Back to cited text no. 16    
17.Hadgraft J. Passive enhancement strategies in topical and transdermal drug delivery. Int J Pharm 1999;184:1-6.  Back to cited text no. 17    

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Correspondence Address:
B M Dinesh
K.L.E. Society's College of Pharmacy, II block, Rajajinagar, Bangalore- 560 010
India
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DOI: 10.4103/0973-8398.41563

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