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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Development and In vitro Evaluation of Nifedipine Gel Formulations for Anorectal Applications

Author(s): Nuray Bagci, Zerrin Sezgin Bayindir, Ozge Inal, Nurten Altanlar and Nilufer Yuksel*

Volume 17, Issue 2, 2020

Page: [126 - 139] Pages: 14

DOI: 10.2174/1567201817666200102125242

Price: $65

Abstract

Objective: Current study focuses on the formulation and characterization of lipophilic and hydrophilic gel formulations of nifedipine to treat anal fissure via anodermal application.

Methods: Lipophilic gels were prepared with Aerosil grades as gelling agents in bulk oils. Polyethylene glycols, hydroxypropyl methylcellulose, and Carbopol® 974P were used as gelling agents in water and propylene glycol for forming hydrophilic gels. The effect of repeated Freeze-Thaw Cycles (FT-C) on microstructures of the gels was investigated by examining viscosity, rheology and textural properties. Aerosil 200 containing lipophilic gels exhibited thixotropic behavior with plastic flow properties and higher viscosities.

Result: Accordingly, their compressibility and adhesiveness increased. FT-C caused notable changes in microstructures and textural properties of the lipophilic gels excluding the formulation containing Aerosil 200-in-isopropyl myristate. Among the hydrophilic gels, the viscosity of Carbopol® 974P gels increased depending on the amount of polymer, triethanolamine and water; these gels featured plastic flow without thixotropic behavior. Their compressibility and adhesiveness were higher than other gel formulations with stable post-FT-C characteristics. The higher flux values of nifedipine were observed from water containing Carbopol® 974P gel.

Conclusion: The results of the stability tests showed that the Carbopol® 974P gel had a longer shelf life than the Aerosil 200-in-isopropyl myristate gel.

Keywords: Nifedipine, anal fissure, anorectal gel, texture analysis, rheology, freeze-thaw cycle.

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[1]
Beaty, J.S.; Shashidharan, M. Anal fissure. Clin. Colon Rectal Surg., 2016, 29(1), 30-37.
[http://dx.doi.org/10.1055/s-0035-1570390] [PMID: 26929749]
[2]
Altomare, D.F.; Binda, G.A.; Canuti, S.; Landolfi, V.; Trompetto, M.; Villani, R.D. The management of patients with primary chronic anal fissure: A position paper. Tech. Coloproctol., 2011, 15(2), 135-141.
[http://dx.doi.org/10.1007/s10151-011-0683-7] [PMID: 21538013]
[3]
Leong, A.P.K. Pharmacological treatment of anal fissure-a future role in primary care. Singapore Med. J., 2003, 44(3), 136-137.
[PMID: 12953727]
[4]
Klin, B.; Abu-Kishk, I.; Efrati, Y.; Lotan, G. Nifedipine gel with lidocaine in the treatment of anal fissure in children: A pilot study and review of the literature.Complementary Pediatrics; Ozdemir, O., Ed.; IntechOpen Ltd.: London, 2012, pp. 53-70.
[http://dx.doi.org/10.5772/33713]
[5]
Steele, S.R.; Madoff, R.D. Systematic review: The treatment of anal fissure. Aliment. Pharmacol. Ther., 2006, 24(2), 247-257.
[http://dx.doi.org/10.1111/j.1365-2036.2006.02990.x] [PMID: 16842451]
[6]
Jensen, S.L. Treatment of first episodes of acute anal fissure: Prospective randomised study of lignocaine ointment versus hydrocortisone ointment or warm sitz baths plus bran. Br. Med. J. (Clin. Res. Ed.), 1986, 292(6529), 1167-1169.
[http://dx.doi.org/10.1136/bmj.292.6529.1167] [PMID: 3011180]
[7]
Bhardwaj, R.; Parker, M.C. Modern perspectives in the treatment of chronic anal fissures. Ann. R. Coll. Surg. Engl., 2007, 89(5), 472-478.
[http://dx.doi.org/10.1308/003588407X202137] [PMID: 17688717]
[8]
Jonas, M.; Neal, K.R.; Abercrombie, J.F.; Scholefield, J.H. A randomized trial of oral vs. topical diltiazem for chronic anal fissures. Dis. Colon Rectum, 2001, 44(8), 1074-1078.
[http://dx.doi.org/10.1007/BF02234624] [PMID: 11535842]
[9]
Lindsey, I.; Cunningham, C.; Jones, O.M.; Francis, C.; Mortensen, N.J. Fissurectomy-botulinum toxin: A novel sphincter-sparing procedure for medically resistant chronic anal fissure. Dis. Colon Rectum, 2004, 47(11), 1947-1952.
[http://dx.doi.org/10.1007/s10350-004-0693-x] [PMID: 15622590]
[10]
Katsinelos, P.; Papaziogas, B.; Koutelidakis, I.; Paroutoglou, G.; Dimiropoulos, S.; Souparis, A.; Atmatzidis, K. Topical 0.5% nifedipine vs. lateral internal sphincterotomy for the treatment of chronic anal fissure: Long-term follow-up. Int. J. Colorectal Dis., 2006, 21(2), 179-183.
[http://dx.doi.org/10.1007/s00384-005-0766-x] [PMID: 16091912]
[11]
Dhawan, S.; Chopra, S. Nonsurgical approaches for the treatment of anal fissures. Am. J. Gastroenterol., 2007, 102(6), 1312-1321.
[http://dx.doi.org/10.1111/j.1572-0241.2007.01203.x] [PMID: 17531031]
[12]
Golfam, F.; Golfam, P.; Khalaj, A.; Sayed Mortaz, S.S. The effect of topical nifedipine in treatment of chronic anal fissure. Acta Med. Iran., 2010, 48(5), 295-299.
[PMID: 21287460]
[13]
Antropoli, C.; Perrotti, P.; Rubino, M.; Martino, A.; De Stefano, G.; Migliore, G.; Antropoli, M.; Piazza, P. Nifedipine for local use in conservative treatment of anal fissures: Preliminary results of a multicenter study. Dis. Colon Rectum, 1999, 42(8), 1011-1015.
[http://dx.doi.org/10.1007/BF02236693] [PMID: 10458123]
[14]
Carapeti, E.A.; Kamm, M.A.; Phillips, R.K. Topical diltiazem and bethanechol decrease anal sphincter pressure and heal anal fissures without side effects. Dis. Colon Rectum, 2000, 43(10), 1359-1362.
[http://dx.doi.org/10.1007/BF02236630] [PMID: 11052511]
[15]
Ezri, T.; Susmallian, S. Topical nifedipine vs. topical glyceryl trinitrate for treatment of chronic anal fissure. Dis. Colon Rectum, 2003, 46(6), 805-808.
[http://dx.doi.org/10.1007/s10350-004-6660-8] [PMID: 12794583]
[16]
Lindsey, I. Anal Fissure.Anorectal and Colonic Diseases; Givel, J-C.R.; Mortensen, N; Roche, B., Ed.; Springer: Berlin, Heidelberg, 2010, pp. 325-337.
[http://dx.doi.org/10.1007/978-3-540-69419-9_20]
[17]
Jones, D.S.; Woolfson, A.D.; Brown, A.F. Textural analysis and flow rheometry of novel, bioadhesive antimicrobial oral gels. Pharm. Res., 1997, 14(4), 450-457.
[http://dx.doi.org/10.1023/A:1012091231023] [PMID: 9144730]
[18]
Flynn, G.L. Cutaneous and transdermal delivery-Processes and systems of delivery. In: Modern Pharmaceutics; 4th ed; Banker, G.S.; Rhodes, C.T., Eds.; Marcel Dekker, Inc.: New York, 2002.
[http://dx.doi.org/10.1201/9780824744694.ch8]
[19]
Pena, L.E. Gel dosage forms: Theory, Formulation, and processing. Topical Drug Delivery Formulations; Osborne, D.W; Amann, A.H., Ed.; Marcel Dekker, Inc.: New York, 1989, pp. 381-388.
[http://dx.doi.org/10.1201/b14194-22]
[20]
The International Pharmacopoeia. 2018.https://www.who.int/phint
[21]
Walters, K.A.; Brain, K.R. Dermatological formulation and transdermal systems.Dermatological and Transdermal Formulations; Walters, K.A., Ed.; Marcel Dekker, Inc.: New York, 2002.
[http://dx.doi.org/10.1201/9780824743239.ch7]
[22]
Dassanayake, L.S.K.; Kodali, D.R.; Ueno, S. Formation of oleogels based on edible lipid materials. Curr. Opin. Colloid Interface Sci., 2011, 16, 432-439.
[http://dx.doi.org/10.1016/j.cocis.2011.05.005]
[23]
Gravelle, A.J.; Barbut, S.; Marangoni, A.G. Ethylcellulose oleogels: Manufacturing considerations and effects of oil oxidation. Food Res. Int., 2012, 48, 578-583.
[http://dx.doi.org/10.1016/j.foodres.2012.05.020]
[24]
Zetzl, A.K.; Gravelle, A.J.; Kurylowicz, M.; Dutcher, J.; Barbut, S.; Marangoni, A.G. Microstructure of ethylcellulose oleogels and its relationship to mechanical properties. Food Structure, 2014, 2, 27-40.
[http://dx.doi.org/10.1016/j.foostr.2014.07.002]
[25]
Baykara, T.; Yuksel, N. The preparation of prolonged action formulations in the form of semi solid matrix into hard gelatin capsules of oxprenolol II. Thixocap method. Drug Dev. Ind. Pharm., 1992, 18, 233-243.
[http://dx.doi.org/10.3109/03639049209043696]
[26]
Islam, M.T.; Rodríguez-Hornedo, N.; Ciotti, S.; Ackermann, C. Rheological characterization of topical carbomer gels neutralized to different pH. Pharm. Res., 2004, 21(7), 1192-1199.
[http://dx.doi.org/10.1023/B:PHAM.0000033006.11619.07] [PMID: 15290859]
[27]
Chu, J.S.; Amidon, G.L.; Weiner, N.D.; Goldberg, A.H. Mixture experimental design in the development of a mucoadhesive gel formulation. Pharm. Res., 1991, 8(11), 1401-1407.
[http://dx.doi.org/10.1023/A:1015853223929] [PMID: 1798677]
[28]
Bonacucina, G.; Martelli, S.; Palmieri, G.F. Rheological, mucoadhesive and release properties of Carbopol gels in hydrophilic cosolvents. Int. J. Pharm., 2004, 282(1-2), 115-130.
[http://dx.doi.org/10.1016/j.ijpharm.2004.06.012] [PMID: 15336387]
[29]
A-sasutjarit. R.; Sirivat, A.; Vayumhasuwan, P. Viscoelastic properties of Carbopol 940 gels and their relationships to piroxicam diffusion coefficients in gel bases. Pharm. Res., 2005, 22(12), 2134-2140.
[http://dx.doi.org/10.1007/s11095-005-8244-2] [PMID: 16215775]
[30]
2011.https://www.lubrizol.com
[31]
Squillante, E.; Needham, T.; Zia, H. Solubility and in vitro transdermal permeation of nifedipine. Int. J. Pharm., 1997, 159, 171-180.
[http://dx.doi.org/10.1016/S0378-5173(97)00282-2]
[32]
Guidance for Industry. Nonsterile Semisolid Dosage Forms, Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In vitro Release Testing and In vivo Bioequivalence Documentation. Food and Drug Administration, Center for Drug Evaluation and Research; CDER, 1997.
[33]
Ocak, F.; Ağabeyoğlu, I. Development of a membrane-controlled transdermal therapeutic system containing isosorbide dinitrate. Int. J. Pharm., 1999, 180(2), 177-183.
[http://dx.doi.org/10.1016/S0378-5173(99)00005-8] [PMID: 10370188]
[34]
Jain, D.; Pathak, K. Design, characterization, and evaluation of meloxicam gel prepared by suspension and solution polymerization using solubility parameter as the basis for development. AAPS PharmSciTech, 2010, 11(1), 133-142.
[http://dx.doi.org/10.1208/s12249-009-9369-0] [PMID: 20077041]
[35]
Squillante, E.; Maniar, A.; Needham, T.; Zia, H. Optimization of in vitro nifedipine penetration enhancement through hairless mouse skin. Int. J. Pharm., 1998, 169, 143-154.
[http://dx.doi.org/10.1016/S0378-5173(98)00110-0]
[36]
EMA - European Medicines Agency. 2008.www.emea.europa.eu
[37]
Moore, J.W.; Flanner, H.H. Mathematical comparison of dissolution profiles. Pharm. Technol., 1996, ((June)), 64-74.
[38]
CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-First Informational Supplement CLSI document M100- S21 (ISBN 1-56238-742-1). Clinical and Laboratory Standards Institute, 2011. Wayne, PA, 19087 USA
[39]
Elsner, P. 2011 40, pp. Anatomical and physiological basis of topical therapy of the mucosa. Topical Applications and the Mucosa. Curr. Probl. Dermatol. Basel, Karger, , 1-8.
[http://dx.doi.org/10.1159/000321038]
[40]
McDaid, D.M.; Deasy, P.B. An investigation into the transdermal delivery of nifedipine. Pharm. Acta Helv., 1996, 71(4), 253-258.
[http://dx.doi.org/10.1016/S0031-6865(96)00022-2] [PMID: 8921743]
[41]
Mak, I.T.; Weglicki, W.B. Comparative antioxidant activities of propranolol, nifedipine, verapamil, and diltiazem against sarcolemmal membrane lipid peroxidation. Circ. Res., 1990, 66(5), 1449-1452.
[http://dx.doi.org/10.1161/01.RES.66.5.1449] [PMID: 2335037 ]
[42]
van Zwieten, P.A. The pharmacological properties of lipophilic calcium antagonists. Blood Press. Suppl., 1998, 2, 5-9.
[http://dx.doi.org/10.1080/080370598438999] [PMID: 9850436]
[43]
Divani, M.J.; Patel, K.R.; Patel, N.M. Revıew: Advanced apporoches in semisolid. Int. J. Pharm. Tech. Res., 2012, 4, 104-115.
[44]
Block, L.H. Medicated topicals.Remington: The Science and Practice of Pharmacy, 20th ed; Gennaro, A.R., Ed.; Lippincott Williams and Wilkins: Baltimore, 2000.
[45]
Sanna, V.; Peana, A.T.; Moretti, M.D.L. Development of new topical formulations of diphenhydramine hydrochloride: In vitro diffusion and in vivo preliminary studies. Int. J. Pharm. Tech. Res., 2010, 2, 863-869.
[46]
Sinko, J.P.; Singh, Y. Martin’s Physical Pharmacy and Pharmaceutical Sciences, 6th ed; Lippincott Williams and Wilkins: Baltimore, 2011.
[47]
Martin, A.; Bustamante, P.; Chun, A.H.C. Physical pharmacy, 4th ed; Lippincolt Williams & Wilkins: Baltimore, 1993, pp. 453-476.
[48]
https://www.aerosil.com/sites/lists/RE/DocumentsSI/TI-1163-AEROSIL-for-cable-gels-EN.pdf
[49]
Devarakonda, B.; Li, N.; de Villiers, M.M. Effect of polyamidoamine (PAMAM) dendrimers on the in vitro release of water-insoluble nifedipine from aqueous gels. AAPS PharmSciTech, 2005, 6(3), E504-E512.
[http://dx.doi.org/10.1208/pt060363] [PMID: 16354011]
[50]
Rahman, N.; Azmi, S.N. Validated spectrophotometric method for the assay of nifedipine in bulk and commercial dosage forms. Sci. Asia, 2006, 32, 429-435.
[http://dx.doi.org/10.2306/scienceasia1513-1874.2006.32.429]
[51]
Lefrançois, P.; Ibarboure, E.; Payré, B.; Gontier, E.; Le Meins, J-F.; Schatz, C. Insights into carbopol gel formulations: Microscopy analysis of the microstructure and the influence of polyol additives. J. Appl. Polym. Sci., 2015, 132, 1-7.
[http://dx.doi.org/10.1002/app.42761]
[52]
Shin, S.C.; Kim, J.Y.; Oh, I.J. Mucoadhesive and physicochemical characterization of carbopol-poloxamer gels containing triamcinolone acetonide. Drug Dev. Ind. Pharm., 2000, 26(3), 307-312.
[http://dx.doi.org/10.1081/DDC-100100358] [PMID: 10738647]
[53]
Cevher, E.; Taha, M.A.; Orlu, M.; Araman, A. Evaluation of mechanical and mucoadhesive properties of clomiphene citrate gel formulations containing carbomers and their thiolated derivatives. Drug Deliv., 2008, 15(1), 57-67.
[http://dx.doi.org/10.1080/10717540701829234] [PMID: 18197525]
[54]
Baloglu, E.; Karavana, S.Y.; Senyigit, Z.A.; Guneri, T. Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base. Pharm. Dev. Technol., 2011, 16(6), 627-636.
[http://dx.doi.org/10.3109/10837450.2010.508074] [PMID: 20715905]
[55]
Jones, D.S.; Woolfson, A.D.; Brown, A.F. Textural, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers. Int. J. Pharm., 1997, 151, 223-233.
[http://dx.doi.org/10.1016/S0378-5173(97)04904-1]
[56]
US Pharmacopeia. US Pharmacopeial Convention, Rockville, MD, Chapter 905 2007.

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