Madhur Kulkarni, Vishakha Hastak, Supriya Jadhav


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 Transcutol® 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 , drug content of 99 ± 1.1% and 66%in vitropermeation of doxaover24h. The effect of various enhancers expressed in terms of average flux can be summarized as Transcutol® (10.6 ± 2.1 µg/cm2h)> dimethyl sulfoxide(10.17± 1.2  µg /cm2h) > benzyl alcohol (9.55± 1.3  µg /cm2h) > no enhancer (8.86± 1.1  µg /cm2h)> dimethyl isosorbide (8.21± 1.5 µg /cm2h)>Isostearic acid (7.82 ± 1.4 µg /cm2h) > propylene carbonate (7.67 ± 1.4  µg /cm2h) > oleic acid (7.12 µg ± 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 Transcutol®.


Conclusion: TDDS of doxacomprising HPMC K100LV and PVPK30 in the ratio of3:1 and 5% Transcutol® could serve as a potential TDDS in the treatment of benign prostatic hyperplasia (BPH) and hypertension.


Doxazosinmesylate, transdermal patch, permeation enhancers, polyvinyl pyrrolidone, hydroxypropyl methylcellulose, Transcutol®


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.ClinInterv 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: It’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;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 of 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 Pharmaceutics 2012;12:55-9.

Pupe CG, Do CarmoFA, 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 App 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. Biochimica et 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 Del Rev 2001;48:139-57.

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