Development, physicochemical evaluation, and in vivo permeation studies of topical formulations containing 0.1% tacrolimus
DOI:
https://doi.org/10.1590/Keywords:
Semi-solid pharmaceutical forms, Analytical methodology, Occlusivity test, In vivo permeation, TacrolimusAbstract
The objective of this paper was to develop and evaluate two semi-solid pharmaceutical forms containing 0.1% tacrolimus: cream (CRT01) and gel (GLT01). For the evaluation of physicochemical stability, at times 0, 30, 60 and 90 days, at 23°C and at 40°C, High Performance Liquid Chromatography coupled with a Diode Array Detector (HPLC-DAD) was employed. This method was developed and validated for tacrolimus quantification. The occlusivity test and skin permeation assay were also performed, using an animal model (Wistar rats), and the CRT01 and GLT01 were compared to the 0.1% tacrolimus ointment (PFU01) obtained from the University Pharmacy, Federal University of Rio de Janeiro, Brazil. CRT01 and GLT01 presented a homogeneous aspect and consistency adequate for topical products, along with sensory characteristics above PFU01. They also presented adequate physicochemical stability for 90 days and a lower occlusive effect than PFU01 (p<0.05). CRT01 showed greater affinity for the skin when compared to PFU01 and GLT01, with low systemic absorption. The CRT01 semi-solid formulation was considered the most adequate one to treat patients with atopic dermatitis or other dermatologic inflammatory diseases, promoting rational use of tacrolimus.
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Agência Nacional de Vigilância Sanitária (Anvisa). Resolução da Diretoria Colegiada RDC nº 899, de 29 de maio de 2003. Determinar a publicação do Guia para validação de métodos analíticos e bioanalíticos. Diário Oficial da República Federativa do Brasil, nº 104, 02/06/2003.
Agência Nacional de Vigilância Sanitária (Anvisa). Resolução RE nº 1, de 29 de julho de 2005. Guia para a Realização de Estudos de Estabilidade. Diário Oficial da República Federativa do Brasil , nº 146, 01/08/2005, Seção 1.
Ali SM, Yosipovitch G. Skin pH: from basic science to basic skin care. Acta Derm Venereol. 2013;93(3):261-267.
Alomar A, Corella F, García-Navarro X. Tacrolimus en enfermedades diferentes a la dermatitis atópica. Actas Dermosifiliogr. 2008;99(S2):26-35.
Ansel HC, Popovich NG, Allen LVJR. Formas farmacêuticas e sistemas de liberação de fármacos. Porto Alegre: Artmed; 2007.
Baldo A, Cafiero M, Di Caterino P, Di Costanzo L. Tacrolimus ointment in the management of atopic dermatitis. Clin Cosmet Investig Dermatol. 2009;2:1-7.
Björklund S, Engblom J, Thuresson K, Sparr E. A water gradient can be used to regulate drug transport across skin. J Controlled Release. 2010;143(2):191-200.
Brasil. Farmacopeia Brasileira, 5ª ed. Agência Nacional de Vigilância Sanitária/Fundação Oswaldo Cruz. Brasília: Anvisa, 2010. Aprovada pela Resolução RDC no 49, de 23 de novembro de 2010. Diário Oficial da República Federativa do Brasil , nº 224, 24/11/2010.
Cerqueira-Coutinho C, Santos-Oliveira R, Santos EP, Mansur CR. Development of a photoprotective and antioxidant nanoemulsion containing chitosan as an agent for improving skin retention. Eng Life Sci. 2015;15(6):593-604.
Dragicevic N, Maibach H. Percutaneous penetration enhancers drug penetration into/through the skin: methodology and general considerations. Berlin: Springer-Verlag Berlin Heidelberg; 2017.
Duncan CN, Riley TV, Carson KC, Budgeon CA, Siffleet J. The effect of an acidic cleanser versus soap on the skin pH and micro-flora of adult patients: A non-randomised two group crossover study in an intensive care unit. Intensive Crit Care Nurs. 2013;29(5):291-296.
Femenía-Font A, Balaguer-Fernández C, Merino V, Rodilla V, López-Castellano A. Effect of chemical enhancers on the in vitro percutaneous absorption of sumatriptan succinate. Eur J Pharm Biopharm. 2005;61(1-2):50-55.
Fernándes-Montes EA. Técnicas y procedimientos en formulación magistral dermatológica. Madrid: Ed. E. Alía, 2005. 342p.
Goebel AB, Neubert RHH, Wohlrab J. Dermal targeting of tacrolimus using colloidal carrier systems. Int J Pharm. 2011;404(1-2):159-168.
Gontijo B, Duarte IAG, Sittart JAS, Pires MC, Takaoka R, Cestari SCP, et al. Avaliação da eficácia e segurança do tacrolimo pomada 0,03% no tratamento da dermatite atópica em pacientes pediátricos. An Bras Dermatol. 2008;83(6):511-519.
Guiling Li; Chao Fan; Xinru Li; Yating Fan; Xiaoning Wang; Mei Li, et al. Preparation and in Vitro evaluation of tacrolimus-loaded ethosomes. ScientificWorldJournal. 2012;2012:1-6.
Herkenne C, Alberti I, Naika A, Kaliay YN, Mathy FX, Préat V, et al. In vivo methods for the assessment of topical drug bioavailability. Pharm Res. 2008;25(1):87-103.
Lachman L, Lieberman H, Kanig J. Teoria e prática na indústria farmacêutica. Lisboa: Calouste Gulbenkian. 2001.
Macleod AM, Thomson AW. FK506: animmunosuppressant for the 1990s? Lancet. 1991;337(8732):25-27.
Marques TZS, Santos-Oliveira R, Siqueira LBO, Cardoso VS, Freitas ZMF, Barros RCSA, et al. Development and characterization of nanoemulsion containing propranolol for topical delivery. Int J Nanomed. 2018;2018(13):2827-2837.
Martins MRFM, Veiga F. Permeation enhancers in transdermal drug delivery systems: a new application of cyclodextrins. Braz J Pharm Sci. 2002;38(1):33-54.
Medication Guide: Protopic. Deerfield: Astellas Pharma US, Inc; 2011[accessed 20 jul 2019]. Available in: Available in: http://www.gov/drugsatfda_docs/label/2011/050777s018lbl.pdf.accessdata.fda
» http://www.gov/drugsatfda_docs/label/2011/050777s018lbl.pdf.accessdata.fda
Melo A, Quaresma CH, Costa C, Santos EP, Leal FD, Homsani F, et al. Memento Terapêutico da Farmácia Universitária da UFRJ. Rio de Janeiro: Faculdade de Farmácia da Universidade Federal do Rio de Janeiro; 2016.
Möller A, Iwasaki K, Kawamura A, Teramura Y, Shiraga T, Hata T, et al. The disposition of 14C-labeled tacrolimus after intravenous and oral administration in healthy human subjects. Drug Metab Dispos. 1999;27(6):633-636.
Mumford PB, Mumford RM. Physical properties of ointment bases. Br J Dermatol. 1941;53(2):45-51.
Nokhodchia A, Shokri J, Dashbolaghi A, Hassan-Zadeh D, Ghafourian T, Barzegar-Jalali M. The enhancement effect of surfactants on the penetration of lorazepam through rat skin. Int J Pharm . 2002;250(2):359-369.
Ortonne JP, Kerkhof PCM, Prinz JC, Bieber T, Lahfa M, Rubins A, et al. 0.3% tacrolimus gel and 0.5% tacrolimus cream show efficacy in mild to moderate plaque psoriasis: results of a randomized, open-label, observer-blinded study. Acta Derm Venereol . 2006;86(1):29-33.
Panchagnula R, Desu H, Jain A, Khandavilli S. Effect of lipid bilayer alteration on transdermal delivery of a high-molecular-weight and lipophilic drug: studies with paclitaxel. J Pharm Sci. 2004;93(9):2177-2183.
Pople PV, Singh KK. Targeting tacrolimus to deeper layers of skin with improved safety for treatment of atopic dermatitis - Part II: In vivo assessment of dermato pharmacokinetics, biodistribution and efficacy. Int J Pharm . 2012;434(1-2):70-79.
Sánchez-Pérez J. Datos de seguridad del tacrolimus: presente y futuro. Actas Dermosifiliogr . 2008;99(S2):19- 25.
Sang GL, Jong BK, Sung RK, Chae JK, Dong WY, Ho YY, et al. Enhanced topical delivery of tacrolimus by a carbomer hydrogel formulation with transcutol P. Drug Dev Ind Pharm. 2016;42(10):1636-1642.
Segger D, Abmus U, Brock M, Erasmy J, Finkel P, Fitzner A, et al. Multicenter study on measurement of the natural pH of the skin surface. Int J Cosmet Sci. 2008;30(1):75-80.
Simonsen L, Hoy G, Didriksen E, Persson J, Melchior N, Hansen J. Development of a new formulation combining Calcipotriol and Betamethasone Dipropionate in an ointment vehicle. Drug Dev Ind Pharm . 2004;30(10):1095-1102.
Sparavigna A, Setaro M, Gualandri V. Cutaneous pH in children affected by atopic dermatitis and in healthy children: a multicenter study. Skin Res Technol. 2006;(4):221-227.
Teeranachaideekul V, Boonme P, Souto EB, Müller RH, Junyaprasert VB. Influence of oil content on physicochemical properties and skin distribution of Nile red-loaded NLC. J Controlled Release . 2008;128(2):134-141.
Teixeira J, Freitas ZMF, Monteiro MSSB, Vermelho AB, Ricci-Junior E, Santos EP. Development and characterizationofphotoprotectiveformulationscontaining keratin particles. Braz J Pharm Sci. 2019;55:e17649.
Trissel L. Trissel’sTM stability of compounded formulations. Washington: American Pharmacists Association. 2012. United States Pharmacopeia 31. United States Pharmacopeial Convention.
Vissers WHPM, Vlijmen I, Erp PEJ, Jong EMGJ, Kerkhof PCM. Topical treatment of mild to moderate plaque psoriasis with 0.3% tacrolimus gel and 0.5% tacrolimus cream: the effect on SUM score, epidermal proliferation, keratinization, T-cell subsets and HLA-DR expression. Br J Dermatol . 2008;158(4):705-712.
Wissing S, Müller R. The influence of the crystalinity of lipid nanoparticles on their occlusive properties. Int J Pharm . 2002;242(1-2):377-379.
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