DEVELOPMENT AND CHARACTERIZATION OF TRANSDERMAL DELIVERY SYSTEM OF DOXAZOSIN MESYLATE
Keywords:Doxazosinmesylate, Transdermal patch, Permeation enhancers, Polyvinyl pyrrolidone, Hydroxypropyl methylcellulose, Nil
Objective: The study involved development of transdermal delivery system (TDDS) of doxazosinmesylate (doxa) to achieve effective systemic delivery of the drug.
Methods: TDDS of doxa was prepared using hydroxypropyl methyl cellulose (HPMC) K100LV and polyvinyl pyrrolidone (PVP) K30 in 3:1 ratio solvent casting method. The formulation was evaluated for folding endurance, moisture uptake, pH, drug content and in vitro permeation. Various permeation enhancers were incorporated at 5% w/w concentration into the patch formulationto study their impact on the drug permeation. The TDDS made with TranscutolÂ® as an enhancer was subjected to accelerated stability studies and in vivo skin irritation studies.
Results: The developed TDDS showed folding endurance of 170, moisture uptakeof 15.7%, pH of 6.3, and drug content of 99Â±1.1% and 66% in vitro permeation of doxa over 24h. The effect of various enhancers expressed in terms of average flux can be summarized as TranscutolÂ® (10.6Â±2.1 Âµg/cm2h)>dimethyl sulfoxide(10.17Â±1.2 Âµg/cm2h)>benzyl alcohol (9.55Â±1.3 Âµg/cm2h)>no enhancer (8.86Â±1.1 Âµg/cm2h)>dimethyl isosorbide (8.21Â±1.5 Âµg/cm2h)>Isostearic acid (7.82Â±1.4 Âµg/cm2h)>propylene carbonate (7.67Â±1.4 Âµg/cm2h)>oleic acid (7.12 ÂµgÂ±0.8/cm2h). The formulation was found to be stable during the accelerated stability studies. In vivo studies indicated absence of skin irritation effect the TDDS containing TranscutolÂ®.
Conclusion: TDDS of doxa comprising HPMC K100LV and PVPK30 in the ratio of 3:1 and 5% TranscutolÂ® could serve as a potential TDDS in the treatment of benign prostatic hyperplasia (BPH) and hypertension.
Walters KA, Brain KR. Topical and transdermal delivery. In: Gibson M. editor. Pharmaceutical preformulation and formulation. 2nd ed. New York: Informa Healthcare Inc; 2009. p. 475.
Tanwar H, Sachdeva R. Transdermal drug delivery system: a review. Int J Pharm Sci Res 2016;7:2274-90.
Ravichandran V, Manivannan S. Wound healing potential of transdermal patches containing bioactive fraction from the bark of Ficus racemosa. Int J Pharm Pharm Sci 2016;6:326-32.
Jhawat V, Saini V, Kamboj S, Maggon N. Transdermal drug delivery systems: approaches and advancement in drug absorption through skin. Int J Pharm Sci Rev Res 2013;20:47-56.
Wilt TJ, MacDonald R. Doxazosin in the treatment of benign prostatic hypertrophy: an update. Clin Interv Aging 2006;1:389-401.
Sweetman SC. Martindale: the complete drug references. 34th ed. London: Pharmaceutical Press; 2005. p. 908-9.
Wolak T, Toledano R, Novack V, Sharon A, Shalev A, Wolak A. Doxazosin to treat hypertension: Itâ€™s time to take it personally-a retrospective analysis of 19495 patients. J Hypertens 2014;32:1132-7.
Current Index of Medical Specialities; Bengaluru (India): CIMS Medica India; 2017. p. 230.
Chaudhari SP, Kotian NR. Formulation development and evaluation of orally disintegrating tablets of doxazosinmesylate. Asian J Pharm 2012;6:266-74.
Preethi GB, Banerjee S, Shivakumar HN, Ravi Kumar M. Formulation of fast dissolving tablets of doxazosin mesylate drug by direct compression method. Int J Appl Pharm 2017;9:22-8.
Kim Ju HJ, Oh T, Rhee Y, Chi S, Park E. Preparation and evaluation of sustained release doxazosin mesylate pellets. Chem Pharm Bull 2013;61:371-8.
Lin HL, Lin SY, Lin YK, Lo YW, Sheu MT. Release characteristics and in vitro-in vivo correlation of pulsatile pattern for a pulsatile drug delivery system activated by membrane rupture via osmotic pressure swelling. Eur J Pharm Biopharm 2008;70:289-301.
Elliot HL, Meredith PA, Reid JL. Pharmacokinetic overview of doxazosin. Am J Cardiol 1987;59:784-814.
Bharkatiya M, Nemal RK. Development and characterization of transdermal patches of metoprololtartrate. Asian J Pharm Clin Res 2010;3:130-4.
Raj A. Formulation evaluation and in vitro permeation studies of transdermal nifedipine from matrix type patches. Int J Pharm Pharm Sci 2014;6:185-8.
Lincy J, Kumar A. Comparison of amlodipine transdermal patches using HPMC and chitosan. Asian J Pharm Clin Res 2014;7:86-90.
Prasanthi D, Lakshmi PK. The effects of chemical enhancers in transdermal penetration of alfuzosin hydrochloride. ISRN Pharm 2012;12:55-9.
Pupe CG, Do Carmo FA, De souse VP. Development of a doxazosin and finasteride transdermal system for combination therapy of benign prostatic hyperplasia. J Pharm Sci 2013;102:4057-64.
Kumar M, Trivedi V, Shukla A, Dev SK. Effect of polymers on the physicochemical and drug release properties of transdermal patches of atenolol. Int J Appl Pharm 2018;4:68-73.
Das SP, Saha P. Design and characterization of transdermal patches of phenformin hydrochloride. Int J Curr Pharm Res 2017;6:90-3.
Patel DS, Patel MV, Patel KM, Patel BA, Patel PA. Transdermal patches: a complete review on transdermal drug delivery system. Int J Pharm Sci Res 2012;1:62-78.
Bathe R, Kapoor R. Transdermal drug delivery system: formulation, development and evaluation-an overview. Int J Biomed Adv Res 2015;6:1-10.
Fayez SM, Gad S, Ghorab MM. Formulation and evaluation of etodolac lecithin organogel transdermal drug delivery systems. Int J Pharm Sci Res 2015;7:325-34.
Van Buskirk GA, Gonzalez MA, Shah VP, Barnhardt S, Barrett C. Scale-up of adhesive transdermal drug delivery systems. Pharm Res 1997;14:848-52.
Draize JH, Woodard GM, 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.
Nanayakkava GR, Bartlett A. The effects of unsaturated fatty acids in benzyl alcohol on the percutaneous permeation of three model penetrants. Int J Pharm 2005;301:129-39.
Squillante E, Maniar A, Needham T. Codiffusion of propylene glycol and dimethyl isosorbide in hairless mouse skin. Eur J Pharm Biopharm 2000;46:265-71.
Karande P, Mitragotri S. Enhancement of transdermal drug delivery via synergistic actions of chemicals. Biochim Biophysica Acta 2009;1788:2362-73.
Saini S, Chauhan SB, Agarwal SS. Recent development in penetration enhancers and techniques in transdermal drug delivery system. J Adv Pharm Educ Res 2014;4:31-40.
Abdelgawad R, Nasr M, Hamza YM, Awa GA. Topical and systemic dermal carriers for psoriasis. Int J Curr Pharm Res 2015;1:4-9.
Siepmann J, Peppas NA. Modelling of drug release from delivery systems based on hydroxypropyl methyl cellulose (HPMC). Adv Drug Delivery Rev 2001;48:139-57.