EFFECT OF HYDROPHILIC AND HYDROPHOBIC POLYMER MATRIX ON THE TRANSDERMAL DRUG DELIVERY OF ETHINYLESTRADIOL AND MEDROXYPROGESTERONE ACETATE
DOI:
https://doi.org/10.22159/ijap.2019v11i1.29886Keywords:
Transdermal, Antifertility, Ethinylestradiol, Medroxyprogesterone acetate, Polyvinylpyrrolidone, Ethylcellulose, Eudragit RL 100 (ERL) and eudragit RS 100 (ERS)Abstract
Objective: The aims of the present study were to develop different matrix patches with various ratios of hydrophilic and hydrophobic polymer combinations such as ethyl cellulose (EC) and polyvinylpyrrolidone (PVP) and eudragit RL 100 (ERL) and eudragit RS 100 (ERS) containing ethinylestradiol and medroxyprogesterone acetate and to perform physicochemical characterization and in vitro permeation studies through rat skin.
Methods: Six formulations (F1 to F6) were developed by varying the concentration of both hydrophilic and hydrophobic polymer and keeping the drug load constant. Physical parameters and drug excipient interaction studies were evaluated in all the formulations. In vitro, skin permeation profiles of ethinylestradiol and medroxyprogesterone acetate from various formulations were simultaneously characterized in a thermostatically controlled modified Franz Diffusion cell. The physicochemical compatibility of the drug and the polymers was studied by differential scanning calorimetry.
Results: The results suggested no physicochemical incompatibility between the drug and the polymers. In vitro permeation studies were performed by using Franz diffusion cells, patches coded as F3 (ethyl cellulose: polyvinylpyrrolidone, 7.5:2.5) and F6 (eudragit RL 100 (ERL) and eudragit RS 100 (ERS), 8:2) can be chosen for further in vivo studies. The results followed Higuchi kinetics (r = 0.9953-0.9979), and the mechanism of release was diffusion mediated. Based on physicochemical and in vitro skin permeation studies of 85.64% (for F3) and 88.62% (for F6) of ethinylestradiol and medroxyprogesterone acetate.
Conclusion: The developed transdermal patches are stable, non-irritating and had increased efficacy of ethinylestradiol and medroxyprogesterone acetate and therefore had a good potential for antifertility treatment.
Downloads
References
Vandenbroucke JP, Rosing J, Bloemenkamp KW, Middeldorp S, Helmerhorst FM, Bouma BN, et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med 2001;344:1527-35.
World Health Organization. Venous thromboembolic disease and combined oral contraceptives: results of an international multicentre case-control study. WHO collaborative study of cardiovascular disease and steroid hormone contraception. Lancet 1995;346:1575–82.
Gomes MP, Deitcher SR. Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review. Arch Intern Med 2004;164:1965–76.
Jick H, Jick SS, Gurewich V, Myers MW, Vasilakis C. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 1995;346:1589-93.
Jick H, Kaye JA, Vasilakis Scaramozza C, Jick SS. Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis. Br Med J 2000;321:1190–5.
World Health Organization. Effect of different progestagens in low oestrogen oral contraceptives on the venous thromboembolic disease. WHO collaborative study of cardiovascular disease and steroid hormone contraception. Lancet 1995;346:1582–8.
Samisoe G. Transdermal hormone therapy: gels and patches. Climacteric 2004;7:347–56.
Sendag F, Terek MC, Karadadas N. Sequential combined transdermal and oral postmenopausal hormone replacement therapies: effects on bleeding patterns and endometrial histology. Arch Gynecol Obstet 2001;265:209–13.
Thassu D, Vyas SP. Controlled transdermal mucolytic delivery system. Drug Dev Ind Pharm 1991;17:561-76.
Wade A, Weller PJ. Handbook of pharmaceutical excipients. Washington DC: American Pharmaceutical Publishing Association; 1994. p. 362-6.
Panigrahi L, Pattnaik S, Ghosal SK. The effect of pH and organic ester penetration enhancers on skin permeation kinetics of terbutaline sulfate from pseudo-latex-type transdermal delivery systems through mouse and human cadaver skins. AAPS PharmSciTech 2005;6:E167-73.
Arora P, Mukherjee P. Design, development, physicochemical, and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt. J Pharm Sci 2002;91:2076-89.
Gupta R, Mukherjee B. Development and in vitro evaluation of diltiazem hydrochloride transdermal patches based on povidone-ethyl cellulose matrices. Drug Dev Ind Pharm 2003;29:1-7.
Beckett AH, Stenlake JB. editors. Practical Pharmaceutical Chemistry. New Delhi: CBC Publishers and Distributors; 1998. p. 284.
Goodman M, Barry BW. Action of penetration enhancers on human skin as assessed by the permeation of model drugs 5-fluorouracil and estradiol.1. Infinite dose technique. J Invest Dermatol 1988;91:323-7.
Wade A, Weller PJ. Handbook of pharmaceutical excipients. Washington DC. American Pharmaceutical Publishing Association; 1994. p. 362-6.
Mutalik S, Udupa N. Glibenclamide transdermal patches: physicochemical, pharmacodynamic, and pharmacokinetic evaluations. J Pharm Sci 2004;93:1577-94.
Katayose S, Kataoka K. Water-soluble polyion complex associates of DNA and poly(ethylene glycol)-poly(L-lysine) block copolymer. Bioconjug Chem 1997;8:702-7.
Ritger PL, Peppas NA. A simple equation for description of solute release, I: Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Controlled Release 1987;5:23-36.
Rao PR, Diwan PV. Formulation and in vitro evaluation of polymeric films of diltiazem hydrochloride and indomethacin for transdermal administration. Drug Dev Ind Pharm 1998;24:327-36.
Draize JH, Woodward G, Calvery HO. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther 1944;82:377-90.
Hardainiyan SW, Kumar KR, Nandy BC, Saxena RI. Design, formulation and in vitro drug release from transdermal patches containing imipramine hydrochloride as the model drug. Int J Pharm Pharm Sci 2017;9:220-5.
Das A, Ahmed AB. Formulation and evaluation of transdermal patch of indomethacin containing patchouli oil as natural penetration enhancer. Asian J Pharm Clin Res 2017;10:320-5.
Chauhan SB, Naved T. Formulation and development of transdermal drug delivery system of ethinylestradiol and medroxyprogesterone acetate for antifertility treatment. Int J ChemTech Res 2017;10:1164-71.
Chauhan SB, Naved T. Formulation and Development of transdermal drug delivery system of antifertility drugs using the combination of polymers. Int J Pharma Bio Sci 2017;8:30-5.
Soujanya C, Satya BL, Reddy ML, Manogna K, Prakash PR, Ramesh A. Formulation and in vitro and in vivo evaluation of transdermal patches of lornoxicam using natural permeation enhancers. Int J Pharm Pharm Sci 2014;6:282-6.
Published
How to Cite
Issue
Section
