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Current Drug Therapy

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ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

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Research Article

Allopurinol Loaded Transferosomes for the Alleviation of Symptomatic After-effects of Gout: An Account of Pharmaceutical Implications

Author(s): Ruchi Tiwari*, Gaurav Tiwari and Rachna Singh

Volume 15, Issue 4, 2020

Page: [404 - 419] Pages: 16

DOI: 10.2174/1574885515666200120124214

Abstract

Background: The present study assessed the transdermal potential of transferosomes loaded with allopurinol for the treatment of gout.

Methods: Transferosomes of allopurinol were composed of different ratios of tween-80, soya lecithin and solvent using a thin-film hydration method. Transferosomes were characterized for Scanning Electron Microscopy (SEM), zeta potential, % entrapment efficiency (%EE), Fourier Transform Infrared Spectroscopy (FTIR), in-vitro drug release and kinetics as well as stability. Then, optimized formulation was incorporated in gel and evaluated for viscosity, pH, extrudability, homogeneity, skin irritation study, spreadability, ex vivo skin permeation study, flux, and stability.

Results: SEM studies suggested that vesicles were spherical and zeta potential were in the range of -11.4 mV to -29.6 mV and %EE was 52.4- 83.87%. FTIR study revealed that there was no interaction between allopurinol and excipients during the preparation of transferosomes. The cumulative percentage of drug release from various transferosomes was ranged from 51.87 to 81.87%. A transferosomal gel of F8 formulation was prepared using dispersion method reported pseudoplastic rheological behavior, optimum pH, spreadability and maximum drug permeation i.e. 79.84% with flux 13.06 g/cm2/hr, followed zero-order release kinetics. Irritation and in-vivo studies of optimized transferosomal gel G8 on rabbits revealed better results than the standard allopurinol.

Conclusion: This research suggested that allopurinol loaded transferosomal gel can be potentially used as a transdermal drug delivery system for the treatment of gout.

Keywords: Allopurinol, transferosomes, transferosomal gel, permeation studies, irritation study, stability of gel.

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[1]
Peterson GM, Boyle RR, Francis HW, et al. Dosage prescribing and plasma oxipurinol levels in patients receiving allopurinol therapy. Eur J Clin Pharmacol 1990; 39(4): 419-21.
[http://dx.doi.org/10.1007/BF00315424] [PMID: 2076730]
[2]
Conaghan PG, Day RO. Risks and benefits of drugs used in the management and prevention of gout. Drug Saf 1994; 11(4): 252-8.
[http://dx.doi.org/10.2165/00002018-199411040-00004] [PMID: 7848545]
[3]
El Maghraby GM, Barry BW, Williams AC. Liposomes and skin: from drug delivery to model membranes. Eur J Pharm Sci 2008; 34(4-5): 203-22.
[http://dx.doi.org/10.1016/j.ejps.2008.05.002] [PMID: 18572392]
[4]
Tiwari R, Tiwari G, Wal P, Wal A, Gupta C. Treatment of warts by topical retinoids: an exploration and meticulosity. Pharm Times 2018; 9: 9-12.
[5]
Brown MB, Martin GP, Jones SA, Akomeah FK. Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv 2006; 13(3): 175-87.
[http://dx.doi.org/10.1080/10717540500455975] [PMID: 16556569]
[6]
Kim A, Lee EH, Choi SH, Kim CK. In vitro and in vivo transfection efficiency of a novel ultradeformable cationic liposome. Biomaterials 2004; 25(2): 305-13.
[http://dx.doi.org/10.1016/S0142-9612(03)00534-9] [PMID: 14585718]
[7]
Garg V, Singh H, Bhatia A, et al. Systematic development of transethosomal gel system of piroxicam: formulation optimization, in vitro evaluation, and ex vivo assessment. AAPS PharmSciTech 2017; 18(1): 58-71.
[http://dx.doi.org/10.1208/s12249-016-0489-z] [PMID: 26868380]
[8]
Kaestli LZ, Wasilewski-Rasca AF, Bonnabry P, Vogt-Ferrier N. Use of transdermal drug formulations in the elderly. Drugs Aging 2008; 25(4): 269-80.
[http://dx.doi.org/10.2165/00002512-200825040-00001] [PMID: 18361538]
[9]
Dubey V, Mishra D, Asthana A, Jain NK. Transdermal delivery of a pineal hormone: Melatonin via elastic liposomes. Biomaterials 2006; 27(18): 3491-6.
[http://dx.doi.org/10.1016/j.biomaterials.2006.01.060] [PMID: 16513163]
[10]
Elsayed MM, Abdallah OY, Naggar VF, Khalafallah NM. Deformable liposomes and ethosomes: Mechanism of enhanced skin delivery. Int J Pharm 2006; 322(1-2): 60-6.
[http://dx.doi.org/10.1016/j.ijpharm.2006.05.027] [PMID: 16806755]
[11]
Malakar J, Sen SO, Nayak AK, Sen KK. Formulation, optimization and evaluation of transferosomal gel for transdermal insulin delivery. Saudi Pharm J 2012; 20(4): 355-63.
[http://dx.doi.org/10.1016/j.jsps.2012.02.001] [PMID: 23960810]
[12]
Rai K, Gupta Y, Jain A, Jain SK. Transfersomes: Self-optimizing carriers for bioactives. PDA J Pharm Sci Technol 2008; 62(5): 362-79.
[PMID: 19055232]
[13]
Srujani C, Anushakanthi M, Murthy VSN. UV spectroscopic method development and validation of allopurinol in bulk and pharmaceutical dosage form. World J Pharm Res 2014; 3(9): 1404-13.
[14]
Kaur CD, Saraf S. Topical vesicular formulations of Curcuma longa extract on recuperating the ultraviolet radiation-damaged skin. J Cosmet Dermatol 2011; 10(4): 260-5.
[http://dx.doi.org/10.1111/j.1473-2165.2011.00586.x] [PMID: 22151933]
[15]
Bagga P, Salman M, Siddiqui HH, Ansari AM, Mehmood T, Singh K. A simple UV spectrophotometric method for the determination of febuxostat in bulk and pharmaceutical formulations. Int J Pharm Sci Res 2011; 2(10): 2655-9.
[16]
Shah NH, Carvajal MT, Patel CI, Infeld MH, Malick AW. Self Emulsifying Drug Delivery Systems (SEDDS) with poly glycolized glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. Int J Pharm 1994; 106(1): 15-23.
[http://dx.doi.org/10.1016/0378-5173(94)90271-2]
[17]
Elkomy MH, El Menshawe SF, Abou-Taleb HA, Elkarmalawy MH. Loratadine bioavailability via buccal transferosomal gel: formulation, statistical optimization, in vitro/in vivo characterization, and pharmacokinetics in human volunteers. Drug Deliv 2017; 24(1): 781-91.
[http://dx.doi.org/10.1080/10717544.2017.1321061] [PMID: 28480758]
[18]
Al Shuwaili AH, Rasool BK, Abdulrasool AA, Rasool A, Alaa A. Optimization of elastic transfersomes formulations for transdermal delivery of pentoxifylline. Eur J Pharm Biopharm 2016; 102: 101-14.
[http://dx.doi.org/10.1016/j.ejpb.2016.02.013] [PMID: 26925505]
[19]
Chourasia MK, Kang L, Chan SY. Nanosized ethosomes bearing ketoprofen for improved transdermal delivery. Results Pharma Sci 2011; 1(1): 60-7.
[http://dx.doi.org/10.1016/j.rinphs.2011.10.002] [PMID: 25755983]
[20]
Tiwari R, Tiwari G, Wal P, Wal A, Maurya P. Development, characterization and transdermal delivery of dapsone and an antibiotic entrapped in ethanolic liposomal gel for the treatment of lapromatous leprosy. Open Nanomed J 2018; 5: 51-15.
[http://dx.doi.org/10.2174/1875933501805010001]
[21]
Chidambaram M, Krishnasamy K. Drug-drug/drug-excipient compatibility studies on curcumin using non-thermal methods. Adv Pharm Bull 2014; 4(3): 309-12.
[PMID: 24754017]
[22]
Singh S, Parashar P, Kanoujia J, Singh I, Saha S, Saraf SA. Transdermal potential and anti-gout efficacy of Febuxostat from niosomal gel. J Drug Deliv Sci Technol 2017; 39: 348-61.
[http://dx.doi.org/10.1016/j.jddst.2017.04.020]
[23]
El-Ridy MS, Yehia SA, Mohsen AM, El-Awdan SA, Darwish AB. Formulation of niosomal gel for enhanced transdermal lornoxicam delivery: in-vitro and in-vivo evaluation. Curr Drug Deliv 2018; 15(1): 122-33.
[http://dx.doi.org/10.2174/1567201814666170224141548] [PMID: 28240177]
[24]
Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 2010; 67(3): 217-23.
[PMID: 20524422]
[25]
Das B, Sen SO, Nayak AK, Sen KK. Transferosomal gel for transdermal delivery of risperidone: Formulation optimization and ex vivo permeation. J Drug Deliv Sci Technol 2017; 38: 59-71.
[http://dx.doi.org/10.1016/j.jddst.2017.01.006]
[26]
Bhulli N, Sharma A. Preparation of novel vesicular carrier ethosomes with glimepiride and their investigation of permeability. Int J of Therapeutic Appli 2012; 2: 1-10.
[27]
Kumar L, Verma R. In vitro evaluation of topical gel prepared using natural polymer. Int J Drug Deliv 2010; 2: 58-63.
[http://dx.doi.org/10.5138/ijdd.2010.0975.0215.02012]
[28]
Patel DJ, Jain VC, Raj HA. Development and validation of spectroscopic method for simultaneous estimation of allopurinol and α-lipoic acid in combination tablet, research and reviews. J Pharm Anal 2014; 3(3): 28-36.
[29]
Kumar TG, Kaur LP. Formulation and evaluation of topical gel of aceclofenac. J Drug Deliv Ther 2013; 3(6): 51-3.
[30]
Kaur LP, Garg R, Gupta GD. Development and evaluation of topical gel of minoxidil from different polymer bases in application of alopecia. Int J Pharm Pharm Sci 2010; 2(3): 43-7.
[31]
Kyo YC, Chung JF. Physicochemical properties of nevirapine loaded solid lipid nanoparticles and nano structured lipid carrier. Colloids sur B biointer 2011; 83: 299-306.
[32]
Ekambaram P, Abdul HS, Abdul A. Formulation and evaluation of solid lipid nanoparticles of ramipril. J Young Pharm 2011; 3(3): 216-20.
[http://dx.doi.org/10.4103/0975-1483.83765] [PMID: 21897661]
[33]
Garg T, Jain S, Singh HP, Sharma A, Tiwary AK. Elastic liposomal formulation for sustained delivery of antimigraine drug: in vitro characterization and biological evaluation. Drug Dev Ind Pharm 2008; 34(10): 1100-10.
[http://dx.doi.org/10.1080/03639040801965079] [PMID: 18663655]
[34]
Singh N, Parashar P, Tripathi CB, Kanoujia J, Kaithwas G, Saraf SA. Oral delivery of allopurinol niosomes in treatment of gout in animal model. J Liposome Res 2017; 27(2): 130-8.
[http://dx.doi.org/10.1080/08982104.2016.1174943] [PMID: 28067087]
[35]
Indora N, Kaushik D. Design, development and evaluation of ethosomal gel of fluconazole for topical fungal infection. Int J Engg Sci Inven Res Develop 2015; 1: 280-305.
[36]
Al-Mahallawi AM, Khowessah OM, Shoukri RA. Nano-transfersomal ciprofloxacin loaded vesicles for non-invasive trans-tympanic ototopical delivery: in-vitro optimization, ex-vivo permeation studies, and in-vivo assessment. Int J Pharm 2014; 472(1-2): 304-14.
[http://dx.doi.org/10.1016/j.ijpharm.2014.06.041] [PMID: 24971692]
[37]
El Maghraby GM, Williams AC, Barry BW. Skin delivery of oestradiol from deformable and traditional liposomes: mechanistic studies. J Pharm Pharmacol 1999; 51(10): 1123-34.
[http://dx.doi.org/10.1211/0022357991776813] [PMID: 10579683]
[38]
Bhasker K, Anbu J. Lipid nanoparticles for transdermal delivery of flurbiprofen: Formulation, in-vitro, ex-vivo and in-vivo studies. Lipid in health and disease 2009; 8(6): 1-15.
[39]
Sanjay J, Padsalg A, Patel K, Moale V. Formulation development and evaluation of fluconazole gel in various polymer base. Asian J Pharm 2007; 1: 63-8.
[40]
Tiwari G, Gupta R, Philip AK, Pathak K. Monolithic periodontal films for simultaneous extended release of metronidazole and doxycycline. Ethio Pharm J 2008; 26: 27-38.
[41]
Singh S, Gadhawala Z. Development of stability indicating RP-RRLC method for determination of allopurinol and its degradation products in solid oral dosage. Int J Pharm Tech Res 2013; 5: 44-53.
[42]
Bharadwaj R, Das PJ, Pal P, Mazumder B. Topical delivery of paclitaxel for treatment of skin cancer. Drug Dev Ind Pharm 2016; 42(9): 1482-94.
[http://dx.doi.org/10.3109/03639045.2016.1151028] [PMID: 26850463]
[43]
Shah R, Eldridge D, Palombo E, Harding I. Optimisation and stability assessment of solid lipid nanoparticles using particle size and zeta potential. J Physiol Sci 2014; 25: 59-75.
[44]
Averineni RK, Shavi GV, Gurram AK, et al. PLGA 50:50 nanoparticles of paclitaxel: Development, in vitro anti-tumor activity in BT-549 cells and in vivo evaluation. Bull Mater Sci 2012; 35: 319-26.
[http://dx.doi.org/10.1007/s12034-012-0313-7]
[45]
Pandita D, Ahuja A, Lather V, et al. Development of lipid-based nanoparticles for enhancing the oral bioavailability of paclitaxel. AAPS PharmSciTech 2011; 12(2): 712-22.
[http://dx.doi.org/10.1208/s12249-011-9636-8] [PMID: 21637945]
[46]
Lu K, Xie S, Han S, et al. Preparation of a nano emodin transfersome and study on its anti-obesity mechanism in adipose tissue of diet-induced obese rats. J Transl Med 2014; 12: 72.
[http://dx.doi.org/10.1186/1479-5876-12-72] [PMID: 24641917]
[47]
Gupta A, Prajapati SK, Balamurugan M, Singh M, Bhatia D. Design and development of a proniosomal transdermal drug delivery system for Captopril. Trop J Pharm Res 2007; 6: 687-93.
[http://dx.doi.org/10.4314/tjpr.v6i2.14647]
[48]
Ebrahimi HA, Javadzadeh Y, Hamidi M, Jalali MB. Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles. Daru 2015; 23: 46.
[http://dx.doi.org/10.1186/s40199-015-0128-3] [PMID: 26392174]
[49]
Zeb A, Qureshi OS, Yu CH, et al. Enhanced anti-rheumatic activity of methotrexate-entrapped ultradeformable liposomal gel in adjuvant-induced arthritis rat model. Int J Pharm 2017; 525(1): 92-100.
[http://dx.doi.org/10.1016/j.ijpharm.2017.04.032] [PMID: 28428089]
[50]
Luo Y, Chen D, Ren L, Zhao X, Qin J. YiFan L. Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. J Control Release 2006; 114(1): 53-9.
[http://dx.doi.org/10.1016/j.jconrel.2006.05.010] [PMID: 16828192]
[51]
El Maghraby GMM, Williams AC, Barry BW. Skin delivery of 5-fluorouracil from ultradeformable and standard liposomes in-vitro. J Pharm Pharmacol 2001; 53(8): 1069-77.
[http://dx.doi.org/10.1211/0022357011776450] [PMID: 11518016]
[52]
Kovacevic A, Savic S, Vuleta G, Müller RH, Keck CM. Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): effects on size, physical stability and particle matrix structure. Int J Pharm 2011; 406(1-2): 163-72.
[http://dx.doi.org/10.1016/j.ijpharm.2010.12.036] [PMID: 21219990]
[53]
El Zaafarany GM, Awad GA, Holayel SM, Mortada ND. Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery. Int J Pharm 2010; 397(1-2): 164-72.
[http://dx.doi.org/10.1016/j.ijpharm.2010.06.034] [PMID: 20599487]
[54]
Jain S, Jain P, Umamaheshwari RB, Jain NK. Transfersomes--a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation. Drug Dev Ind Pharm 2003; 29(9): 1013-26.
[http://dx.doi.org/10.1081/DDC-120025458] [PMID: 14606665]
[55]
Trotta M, Peira E, Carlotti ME, Gallarate M. Deformable liposomes for dermal administration of methotrexate. Int J Pharm 2004; 270(1-2): 119-25.
[http://dx.doi.org/10.1016/j.ijpharm.2003.10.006] [PMID: 14726128]
[56]
Koda-Kimble MA, Young LY, Alldredge BK, et al. Applied therapeutics. Lippincott Williams & Wilkins 2009.
[57]
Zeb A, Qureshi OS, Kim HS, Cha JH, Kim HS, Kim JK. Improved skin permeation of methotrexate via nanosized ultradeformable liposomes. Int J Nanomedicine 2016; 11: 3813-24.
[http://dx.doi.org/10.2147/IJN.S109565] [PMID: 27540293]
[58]
Sarwa KK, Mazumder B, Rudrapal M, Verma VK. Potential of capsaicin-loaded transfersomes in arthritic rats. Drug Deliv 2015; 22(5): 638-46.
[http://dx.doi.org/10.3109/10717544.2013.871601] [PMID: 24471764]
[59]
Abdallah M. Transferosomes as a transdermal drug delivery system for enhancement the antifungal activity of nyastatin. Int J Pharm Pharm Sci 2013; 5: 560-7.
[60]
Tripathi KD. Essentials of Medical Pharmacology. Jaypee Brothers 2003.
[61]
Agudelo CA, Wise CM. Crystal-associated arthritis in the elderly. Rheum Dis Clin North Am 2000; 26(3): 527-46. [vii.]
[http://dx.doi.org/10.1016/S0889-857X(05)70155-1] [PMID: 10989511]
[62]
Alvi IA, Madan J, Kaushik D, Sardana S, Pandey RS, Ali A. Comparative study of transfersomes, liposomes, and niosomes for topical delivery of 5-fluorouracil to skin cancer cells: preparation, characterization, in-vitro release, and cytotoxicity analysis. Anticancer Drugs 2011; 22(8): 774-82.
[http://dx.doi.org/10.1097/CAD.0b013e328346c7d6] [PMID: 21799471]
[63]
Florey K. Analytical Profiles of Drug Substances. Academic Press 1976.
[64]
Fam AG. Gout in the elderly. Clinical presentation and treatment. Drugs Aging 1998; 13(3): 229-43.
[http://dx.doi.org/10.2165/00002512-199813030-00006] [PMID: 9789727]
[65]
Singh HP, Utreja P, Tiwary AK, Jain S. Elastic liposomal formulation for sustained delivery of colchicine: in vitro characterization and in vivo evaluation of anti-gout activity. AAPS J 2009; 11(1): 54-64.
[http://dx.doi.org/10.1208/s12248-008-9078-8] [PMID: 19191031]
[66]
Cameron JS, Simmonds HA. Use and abuse of allopurinol. Br Med J (Clin Res Ed) 1987; 294(6586): 1504-5.
[http://dx.doi.org/10.1136/bmj.294.6586.1504] [PMID: 3607420]
[67]
Zheng Y, Hou SX, Chen T, Lu Y. Preparation and characterization of transfersomes of three drugs in vitro Zhongguo Zhongyao Zazhi 2006; 31(9): 728-31.
[PMID: 17048677]
[68]
Vasan RS, Seshadri S. Textbook of Medicine. Orient Longman 1998.
[69]
Vanić Ž, Hafner A, Bego M, Škalko-Basnet N. Characterization of various deformable liposomes with metronidazole. Drug Dev Ind Pharm 2013; 39(3): 481-8.
[http://dx.doi.org/10.3109/03639045.2012.670247] [PMID: 22455377]
[70]
Cevc G, Blume G, Schatzlein A. Transferosomes mediated transepidermal delivery improves the regiospecificity and biological activity of corticosteroids in-vivo. J Control Release 1997; 45: 211-26.
[http://dx.doi.org/10.1016/S0168-3659(96)01566-0]
[71]
Mishra D, Garg M, Dubey V, Jain S, Jain NK. Elastic liposomes mediated transdermal delivery of an anti-hypertensive agent: propranolol hydrochloride. J Pharm Sci 2007; 96(1): 145-55.
[http://dx.doi.org/10.1002/jps.20737] [PMID: 16960826]
[72]
nternational Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use, Validation of analytical procedures: Text and Methodology. ICH-Q2B, Geneva 1996.
[73]
Jain S, Jain N, Bhadra D, Tiwary AK, Jain NK. Transdermal delivery of an analgesic agent using elastic liposomes: preparation, characterization and performance evaluation. Curr Drug Deliv 2005; 2(3): 223-33.
[http://dx.doi.org/10.2174/1567201054368020] [PMID: 16305424]
[74]
Jain S, Sapre R, Umamaheshwari RB, Jain NK. Protransfersomes for effective transdermal delivery of norgestrel preparation and in vitro characterization. Indian J Pharm Sci 2003; 65: 153-61.
[75]
USP 27/ National Formulary 22, Asian Edn. United State Pharmacopoeial Convention Inc. Rockville 2004.
[76]
Trotta M, Peira E, Debernardi F, Gallarate M. Elastic liposomes for skin delivery of dipotassium glycyrrhizinate. Int J Pharm 2002; 241(2): 319-27.
[http://dx.doi.org/10.1016/S0378-5173(02)00266-1] [PMID: 12100859]
[77]
Sigurgeirsson B, Ghannoum M. Therapeutic potential of TDT 067 (terbinafine in Transfersome): a carrier-based dosage form of terbinafine for onychomycosis. Expert Opin Investig Drugs 2012; 21(10): 1549-62.
[http://dx.doi.org/10.1517/13543784.2012.711315] [PMID: 22876754]

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