Sakhare AD, Biyani KR, Sudke SG
Sakhare AD1, Biyani KR1, Sudke SG2
1Anuradha College of Pharmacy, Chikhli 443201, Maharashtra, India.
2GES’s Satara College of Pharmacy, Satara 415004, Maharashtra, India.
Volume - 13,
Issue - 10,
Year - 2020
The transdermal adhesive patches of carvedilol were designed using pressure sensitive acrylic adhesives such as DUROTAK® 87-235A, DUROTAK® 87-8301 and DUROTAK® 87-4287. The patches were evaluated for physicochemical characterization, in-vitro drug permeation across dialysis membrane and ex-vivo drug permeation through the pork ear skin using diffusion cell, stability studies and skin irritability study. The Scanning Electron Microscopy (SEM) of patches does not show any evidence of recrystallization indicating the presence of drug in the molecular form in the adhesive matrix. The physicochemical properties of patches were found to be in acceptable limit. Among the three acrylic adhesives used, DUROTAK® 87-4287 exhibited maximum flux (8.47 ± 0.18 µg/cm2.hr). To enhance the drug permeation, peppermint oil was used as penetration enhancers (2%) in the patches. Out of those, formulation A6 exhibited a flux of 10.04 ± 0.83 µg/cm2.hr revealing that formulation A6 was the optimized formulation. The patches of A6 formulation showed excellent in-vitro-ex-vivo correlationship. The stability study was carried out using optimized fresh (A6) formulation for 3 months old patches stored at room (25 ± 2 °C/60 ± 5%RH) and at accelerated condition (40 ± 2 °C/75 ± 5%RH). The investigation reveals that the adhesive type patches of carvedilol were stable and devoid of skin irritation and hypersensitive response. Therefore, may serve as a potential drug delivery system for carvedilol.
Cite this article:
Sakhare AD, Biyani KR, Sudke SG. Design and evaluation of adhesive type transdermal patches of Carvedilol. Research J. Pharm. and Tech. 2020; 13(10):4941-4949. doi: 10.5958/0974-360X.2020.00867.7
1. Delgado-Charro MB, Guy RH. Effective use of transdermal drug delivery in children. Advanced Drug Delivery Review. 2014; 73:63–82.
2. Nishida N, et al. Development and evaluation of a monolithic drug-in-adhesive patch for Valsartan. International Journal Pharmaceutics. 2010; 402: 103–109.
3. Delgado-Charro MB and Guy RH. Transdermal drug delivery. In: Drug Delivery and Targetting, Edited by Hillery AM, Lloyd AW and Swarbrick J. Taylor & Francis, London and New York. 2001: 1st ed: pp. 207–236.
4. Wang W, et al. Investigate the control release effect of ion-pair in the development of escitalopram transdermal patch using FT-IR spectroscopy, molecular modeling and thermal analysis. International Journal Pharmaceutics. 2017; 529 (1–2):391–400.
5. Li N, et al. Mechanistic insights of the enhancement effect of sorbitan monooleate on olanzapine transdermal patch both in release and percutaneous absorption processes. European Journal of Pharmaceutical Sciences. 2017; 107:138–147.
6. Hu Y, et al. Development of drug in- adhesive transdermal patch for α-asarone and in vivo pharmacokinetics and efficacy evaluation. Drug Delivery. 2011; 18: 84–89.
7. Jung E, et al. Development of drug-in-adhesive patch formulations for transdermal delivery of fluoxetine: in vitro and in vivo evaluations. International Journal Pharmaceutics. 2015; 487:49–55.
8. Banerjee S, et al. Aspect of adhesives in transdermal drug delivery systems. International Journal Adhesion and Adhesives. 2014; 50:70–84.
9. Schulz M, Fussnegger B, Bodmeier R. Drug release and adhesive properties of crospovidone-containing matrix patches based on polyisobutene and acrylic adhesives. European Journal of Pharmaceutical Sciences. 2010; 41:675–684.
10. Sun Y, et al. A drug-in-adhesive transdermal patch for S-amlodipine free base: in vitro and in vivo characterization. International Journal Pharmaceutics. 2009; 382:165–171.
11. Liu C, et al. A systemic evaluation of drug in acrylic pressure sensitive adhesive patch in vitro and in vivo: the roles of intermolecular interaction and adhesive mobility variation in drug controlled release. Journal of Controlled Release. 2017; 252:83–94.
12. Paule CC, et al. Development of a predictive model for the long-term stability assessment of drug-in-adhesive transdermal films using polar pressure-sensitive adhesives as carrier/matrix. Journal of Pharmaceutical Sciences. 2017; 106 (5):1293–1301.
13. Teodorescu F, et al. Transdermal skin patch based on reduced graphene oxide: a new approach for photothermal triggered permeation of ondansetron across porcine skin. Journal of Controlled Release. 2017; 245:137–146.
14. Ruffolo RR, Feuerstein GZ. Pharmacology of carvedilol: rational for use in hypertension, coronary artery disease, and congestive heart failure. Cardiovascular Drugs Therapeutics. 1997; 11: 247– 256.
15. Thummel KE and Shen DD. Design and optimization of dosage regimens: pharmacokinetic data. In Goodman and Gilman’s The pharmacological basis of therapeutics, Edited by Hardman JG, Limbirel LE and Gilman AG. Mc Graw Hill, New York. 2001; 10th ed: pp. 1936.
16. Landsberg L and Young JB. Physiology and pharmacology of the autonomic nervous system. In Harrison’s Principles of Internal Medicine, Edited by Braunwald E, et al, Mc. Graw Hill, New York. 2001: 15th ed: pp. 447.
17. Lipp R. Selection and use of crystallization inhibitors for matrix-type transdermal drug-delivery systems containing sex steroids. Journal Pharmacy and Pharmacology. 1998; 50: 1343–1349.
18. Kommanaboyina B, Rhodes CT. Trends in stability testing, with emphasis on stability during distribution and storage. Drug Development and Industrial Pharmacy. 1999; 25:857–868.
19. Banerjee S, et al. Accelerated stability testing of a transdermal patch composed of eserine and pralidoxime chloride for prophylaxis against (±)-anatoxin A poisoning. Journal of Food and Drug Analysis. 2014; 22: 264–270.
20. Patel P and Bhaskar VH. Formulation and evaluation of transdermal patches of 18-ß-glycyrrhetic acid. International Journal of Pharmaceutical Sciences and Research 2013; 4(12): 4581-86
21. Mirza F, Lohani A. Formulation and Characterization of Drug in Adhesive Transdermal Patches of Buflomedil Hydrochloride. International Journal of Pharmaceutical Sciences and Research. 2015; 6(10): 4469-78.
22. Prosser JM, Jones BE, Nelson L. Complications of oral exposure to fentanyl transdermal delivery system patches. Journal of Medical Toxicology. 2010; 6:443–447.
23. Zafar S, et al. Transdermal delivery of labetalol hydrochloride: Effect of penetration enhancers. Journal of Pharmacy and Bioallied Sciences. 2010; 2(4) 321-324.
24. Gannu R, Yamsani VV, Yamsani SK, Palem CR, Yamsani MR. Optimization of hydrogels for transdermal delivery of lisinopril by box-behnken statistical design. AAPS PharmSciTech. 2009; 10:505- 514.
25. Bharkatiya M, Nema R, Bhatnagar M. Designing and characterization of drug free patches for transdermal application. International Journal of Pharmaceutical Sciences and Drug Research. 2012; 2: 35–39.
26. Singh A, Bali A. Formulation and characterization of transdermal patches for controlled delivery of duloxetine hydrochloride. Journal of Analytical Science and Technology. 2016; 7: 25-29. (flatness)
27. Taghizadeh SM, Soroushnia A, Mohamadnia F. Preparation and in vitro evaluation of a new fentanyl patch based on functional and non-functional pressure sensitive adhesives. AAPS Pharm SciTech. 2010; 11(1): 278–284.
28. Steven-Fountain AJ, et al. The effect of flexible substrates on pressure-sensitive adhesive performance. International Journal Adhesion and Adhesives. 2002; 22: 423–430.
29. Arora P, Mukherjee BDesign, development, physicochemical and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt. Journal of Pharmaceutical Sciences. 2002; 91:2076-2089.
30. Singh J, Tripathi K, Sakya T. Effect of penetration enhancers on the in-vitro transport of ephedrine through rat skin and human epidermis from matrix based transdermal formulations. Drug Development and Industrial Pharmacy. 1993; 19:1623–1628.
31. Shivaraj A, et al. Design and evaluation of transdermal drug delivery of ketotifen fumarate. International Journal of Pharmaceutical and Biomedical Research. 2010; 1(2): 42-47.
32. Maftoona N, Ramaswamy HS, Marcotte M. Evaluation of factors affecting barrier, mechanical and optical properties of pectin-based films using response surface methodology. Journal of Food Processing Engineering. 2007; 30 (2007) 539–563.
33. Bodmeier R, Paeratakul O. Drug release from laminated polymeric films prepared from aqueous latexes. Journal of Pharmaceutical Sciences. 1990; 10:32–36.
34. Suwanpiodokkul N, Thongnopnua P, Umprayan K. Transdermal delivery of zidovidine (AZT): The effects of vehicles, enhancers, and polymer membranes on permeation across cadaver pig skin. AAPS Pharm Sci Tech 2004; 5(3): 82-89.
35. Moreira TSA, de Sousa VD, Pierre MRB, A novel transdermal delivery system for the anti-inflammatory lumiracoxib: influence of oleic acid on in vitro percutaneous absorption and in vivo potential cutaneous irritation. AAPS PharmSciTech. 2010;11: 621–629.
36. Limpongsa E, Umprayn K. Preparation and evaluation of diltiazem hydrochloride diffusion-controlled transdermal delivery system. AAPS PharmSciTech. 2008; 9 :464–470.
37. Parhi R, Suresh P, Pattnaik S. Pluronic lecithin organogel (PLO) of diltiazem hydrochloride: effect of solvents/penetration enhancers on ex vivo permeation. Drug Delivery and Translational Research. 2016;6: 243–253.
38. Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. European Journal of Pharmaceutical Sciences. 2001; 13:123–133.
39. Sakarkar DM, Dorle AK, Mahajan NM, Sudke SG. Design of sustained release pellets of ferrous fumarate using cow ghee as hot-melt coating agent. International Journal of Pharmaceutical Investigation. 2013; 3(3):3151-3156.
40. Draize JH, Woodword G, Calvery HO. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. Journal of Pharmacology and Experimental Therapeutics. 1944; 82:377–390