Formulation And Evaluation Of Transdermal Patches Of 5-Fluorouracil For The Treatment Of Skin Cancer
Keywords:
formulation, interaction, Stability, Delivery, CancerAbstract
The present study focuses on the formulation and evaluation of transdermal patches of 5-fluorouracil (5-FU) intended for the topical treatment of skin cancer, aiming to enhance localized drug delivery while minimizing systemic side effects. 5-FU, a potent antimetabolite used in chemotherapy, suffers from poor skin permeability and rapid metabolism when administered conventionally. To overcome these limitations, transdermal drug delivery offers a non-invasive and controlled release system that can maintain therapeutic drug levels at the site of action.
Transdermal patches were prepared using solvent casting technique employing various polymers such as hydroxypropyl methylcellulose (HPMC), ethyl cellulose (EC), and polyvinyl alcohol (PVA) either alone or in combinations, along with suitable plasticizers like glycerol or polyethylene glycol (PEG 400). The prepared patches were subjected to a series of physicochemical evaluations including thickness, weight variation, folding endurance, surface pH, drug content uniformity, moisture content, water vapor transmission rate, and in vitro drug release studies using Franz diffusion cell.
Among the different formulations, the patch containing HPMC:EC in a 2:1 ratio exhibited optimal physical properties and sustained drug release up to 24 hours, showing a cumulative drug release of over 85%, indicating a controlled release pattern. The in vitro permeation study demonstrated enhanced skin penetration, and FTIR studies confirmed no significant interaction between 5-FU and the excipients. The stability studies, conducted as per ICH guidelines, showed no significant changes in drug content and appearance over a period of three months.
In conclusion, the formulated transdermal patches of 5-fluorouracil offer a promising alternative to conventional topical or systemic therapies for skin cancer by enabling localized, sustained delivery of the drug with improved patient compliance and reduced systemic toxicity..
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Ceilley, R.I. Mechanisms of action of topical 5-fluorouracil: Review and implications for the treatment of dermatological disorders. J. Dermatol. Treat. 2012, 23, 83–89.
Bagatin, E. 5-fluorouracil for actinic keratoses. Expert Rev. Dermatol. 2010, 5, 131–139.
Kim, S.; Fouladian, P.; Afinjuomo, F.; Song, Y.; Youssef, S.H.; Vaidya, S.; Garg, S. Effect of plasticizers on drug-in-adhesive patches containing 5-fluorouracil. Int. J. Pharm. 2022, 611, 121316
Donnelly, R.F.; McCarron, P.A.; Zawislak, A.A.; Woolfson, A.D. Design and physicochemical characterisation of a bioadhesive patch for dose-controlled topical delivery of imiquimod. Int. J. Pharm. 2006, 307, 318–325.
Kim, S.; Day, C.M.; Song, Y.; Holmes, A.; Garg, S. Innovative Topical Patches for Non-Melanoma Skin Cancer: Current Challenges and Key Formulation Considerations. Pharmaceutics 2023, 15, 2577.
Kathe, K.; Kathpalia, H. Film forming systems for topical and transdermal drug delivery. Asian J. Pharm. Sci. 2017, 12, 487–497.
Chinembiri, T.N.; Gerber, M.; du Plessis, L.; du Preez, J.; du Plessis, J. Topical Delivery of 5-Fluorouracil from Pheroid Formulations and the In vitro Efficacy Against Human Melanoma. AAPS PharmSciTech 2015, 16, 1390–1399.
Mutalik, S.; Shetty, P.K.; Kumar, A.; Kalra, R.; Parekh, H.S. Enhancement in deposition and permeation of fluorouracil through human epidermis assisted by peptide dendrimers. Drug Deliv. 2014, 21, 44–54
Crisóstomo, L.C.C.F.; Carvalho, G.S.G.; Leal, L.K.A.M.; de Araújo, T.G.; Nogueira, K.A.B.; da Silva, D.A.; de Oliveira Silva Ribeiro, F.; Petrilli, R.; Eloy, J.O. Sorbitan Monolaurate–Containing Liposomes Enhance Skin Cancer Cell Cytotoxicity and in Association with Microneedling Increase the Skin Penetration of 5-Fluorouracil. AAPS PharmSciTech 2022, 23, 212
Yamane, M.A.; Williams, A.C.; Barry, B.W. Effects of terpenes and oleic acid as skin penetration enhancers towards 5-fluorouracil as assessed with time; permeation, partitioning and differential scanning calorimetry. Int. J. Pharm. 1995, 116, 237–251.
Peters GJ, Lankelma J, Kok RM. Prolonged retention of high concentrations of 5-fluorouracil in human and murine tumours as compared with plasma. Cancer Chemother Pharmacol. 1993;31(4):269–76.
Holland JF, Frei III E, Bast RC Jr. Cancer medicine. Philadelphia:Lea & Febiger;1993 12. Patzelt A, Antoniou C, Sterry W, Lademann J. Skin penetration from the inside to the outside: a review. Drug Discov Today Dis Mech. 2008; 5(2):e229–35
Schreier H, Bouwstra J. Liposomes and niosomes as topical drug carriers:dermal and transdermal drug delivery. J Control Release. 1994;30 (1):1–15.
Manosroi A, Jantrawut P, Manosroi, J. Antiinflammatory activity of gel containing novel elastic niosomes entrapped with diclofenac diethyl ammonium. Int J Pharm. 2008;360 (1-2):156–63.
Hu C, Rhodes DG. Proniosomes:A novel drug carrier preparation. Int J Pharm. 1999;185(1): 23-35.
El Maghraby, GM, Williams AC.Vesicular systems for delivering conventional small organic molecules and larger macromolecules to and through human skin. Expert Opin Drug Deliv. 2009;6(2):149–63.
C.Hu.D.G.Rhodes. Proniosomes a novel drug carrier preparation, Int J Pharm. 1999;185(1): 23-5.
Fang JY, Yu SY, Wu PC, Huang YB, Tsai YH. In vitro skin permeation of estradiol from various proniosome formulations, Int J Pharm. 2001;215 (1–2):91–9.
JiaYou Fang. In vitro skin permeation of estradiol from various proniosome formulations. Int J Pharm. 2001;215(1-2):91–9.
Alaa EE, Salwa S, Mahmoud G. Proniosomal gel-derived niosomes:an approach to sustain and improve the ocular delivery of brimonidine tartrate;formulation, in vitro characterization, and in vivo pharmacodynamic study. Drug Delivery. 2019;26(1):509–21.
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