Generic placeholder image

Current Drug Delivery

Author(s): Shabina Mahmood, Manal Ali Buabeid, Kaleem Ullah, Ghulam Murtaza*, Abdul Mannan and Shujaat Ali Khan*

DOI: 10.2174/1567201816666190208165511

DownloadDownload PDF Flyer Cite As
Synthesis, Characterization and Safety Profiling of Eudragit-Based pHResponsive Hydrogels: A Promising Platform for Colonic Delivery of Losartan Potassium

Page: [548 - 564] Pages: 17

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Objective: The aim of the present study was to design an efficient delivery system with an anticipated swelling and drug release properties for a prolonged drug release as well as to target colon for various hydrophilic drugs.

Method: For this purpose, the pH-responsive hydrogel comprising a combination of Eudragit and acrylic acid was formed. The hydrogels were characterized for spectral (FTIR), thermal (TGA/DSC), structural (XRD), and morphological (SEM) investigations. Oral tolerability was assessed in rabbits for biocompatibility and oral use of the prepared hydrogels.

Results: The results showed that an increased incorporation of Eudragit and cross-linking agent retorted the swelling, drug loading, and drug release properties at both acid (pH 1.2) and basic pH (pH 6.8 and 7.4) , while acrylic acid presented the inverse results. The oral tolerability and toxicity studies depicted that the developed hydrogels were safe up to 3800 mg/kg body weight and caused no hematological or histopathological changes when compared with the control group.

Conclusion: Therefore, the newly developed formulations presented adequate swelling, drug loading, release behavior, and biocompatibility properties and thus can be used as a promising tool for the colonic delivery of various hydrophilic drugs.

Keywords: Eudragit S-100, acrylic acid, crosslinking, colonic delivery, losartan potassium, drug delivery.

Graphical Abstract

[1]
Ganji, F.; Vasheghani, F.S.; Vasheghani, F.E. Theoretical description of hydrogel swelling: A review. Iran. Polym. J., 2010, 19(5), 375-398.
[2]
Ullah, F.; Othman, M.B.; Javed, F.; Ahmad, Z.; Md Akil, H. Classification, processing and application of hydrogels: A review. Mater. Sci. Eng. C, 2015, 57, 414-433.
[http://dx.doi.org/10.1016/j.msec.2015.07.053] [PMID: 26354282]
[3]
Sohail, M.; Ahmad, M.; Minhas, M.U.; Ali, L.; Munir, A.; Khalid, I. Synthesis and characterization of graft PVA composites for controlled delivery of valsartan. Lat. Am. J. Pharm., 2014, 33(8), 1237-1244.
[4]
Amin, M.C.I.M.; Ahmad, N.; Halib, N.; Ahmad, I. Synthesis and characterization of thermo-and pH-responsive bacterial cellulose/acrylic acid hydrogels for drug delivery. Carbohydr. Polym., 2012, 88, 465-473.
[http://dx.doi.org/10.1016/j.carbpol.2011.12.022]
[5]
Ranjha, N.M.; Ayub, G.; Naseem, S.; Ansari, M.T. Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil. J. Mater. Sci. Mater. Med., 2010, 21(10), 2805-2816.
[http://dx.doi.org/10.1007/s10856-010-4134-1] [PMID: 20686825]
[6]
Paharia, A.; Yadav, A.K.; Rai, G.; Jain, S.K.; Pancholi, S.S.; Agrawal, G.P. Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting. AAPS PharmSciTech, 2007, 8(1), 12.
[http://dx.doi.org/10.1208/pt0801012] [PMID: 17408212]
[7]
Gupta, V.K.; Assmus, M.W.; Beckert, T.E.; Price, J.C. A novel pH- and time-based multi-unit potential colonic drug delivery system. II. Optimization of multiple response variables. Int. J. Pharm., 2001, 213(1-2), 93-102.
[http://dx.doi.org/10.1016/S0378-5173(00)00650-5] [PMID: 11165097]
[8]
Huang, Y.; Lu, J.; Xiao, C. Thermal and mechanical properties of cationic guar gum/poly (acrylic acid) hydrogel membranes. Polym. Degrad. Stabil., 2007, 92(6), 1072-1081.
[http://dx.doi.org/10.1016/j.polymdegradstab.2007.02.011]
[9]
Hussain, T.; Ranjha, N.M.; Shahzad, Y. Swelling and controlled release of tramadol hydrochloride from a pH-sensitive hydrogel. Des. Monomers Polym., 2011, 14(3), 233-249.
[http://dx.doi.org/10.1163/138577211X557521]
[10]
Singh, A.; Deep, A. Formulation and evaluation of nanoparticles containing Losartan potassium. Int. J. Pharm. Res. Tech., 2011, 1(1), 1-8.
[11]
Dash, S.; Murthy, P.N.; Nath, L.; Chowdhury, P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol. Pharm., 2010, 67(3), 217-223.
[PMID: 20524422]
[12]
Vidyadhara, S.; Ramesh, J.; Talamanchi, B.; Pavuluri, P.; Modalavalasa, T.; Kumar, P. Design and evaluation of controlled release losartan potassium microcapsules. J. Pharm. Res., 2013, 6(4), 470-475.
[http://dx.doi.org/10.1016/j.jopr.2013.04.015]
[13]
Shah, S.A.; Sohail, M.; Minhas, M.U.; Rehman, N.U. Khan, S; Hussain, Z.; Mudassir.; Mahmood, A.; Kousar, M.; Mahmood, A. pH-responsive CAP-co-poly (methacrylic acid)-based hydrogel as an efficient platform for controlled gastrointestinal delivery: Fabrication, characterization, in vitro and in vivo toxicity evaluation. Drug Deliv. Transl. Res., 2018, 15, 1-23.
[14]
Bukhari, S.M.H.; Khan, S.; Rehanullah, M.; Ranjha, N.M. Synthesis and characterization of chemically cross-linked acrylic acid/gelatin hydrogels: effect of pH and composition on swelling and drug release In: Int. J. Polym. Sci; , 2015; 2015, . Article ID 187961, 15 pages
[http://dx.doi.org/[http://10.1155/2015/187961]
[15]
Khalid, I.; Ahmad, M.; Minhas, M.U.; Barkat, K.; Sohail, M. Cross‐linked sodium alginate‐g‐poly (Acrylic Acid) structure: A potential hydrogel network for controlled delivery of loxoprofen sodium. Adv. Polym. Technol., 2018, 37(4), 985-995.
[http://dx.doi.org/10.1002/adv.21747]
[16]
Ranjha, N.M.; Mudassir, J. Swelling and aspirin release study: Cross-linked pH-sensitive vinyl acetate-co-acrylic acid (VAC-co-AA) hydrogels. Drug Dev. Ind. Pharm., 2008, 34(5), 512-521.
[http://dx.doi.org/10.1080/03639040701744079] [PMID: 18473234]
[17]
Ullah, K.; Sohail, M.; Murtaza, G.; Khan, S.A. Natural and synthetic materials based CMCh/PVA hydrogels for oxaliplatin delivery: Fabrication, characterization, in-vitro and in-vivo safety profiling. Int. J. Biol. Macromol., 2019, 122, 538-548.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.10.203] [PMID: 30389527]
[18]
Khanum, H.; Ullah, K.; Murtaza, G.; Khan, S.A. Fabrication and in vitro characterization of HPMC-g-poly(AMPS) hydrogels loaded with loxoprofen sodium. Int. J. Biol. Macromol., 2018, 120(Pt B), 1624-1631.
[19]
Ranjha, N.M.; Mudassir, J.; Majeed, S. Synthesis and characterization of polycaprolactone/acrylic acid (PCL/AA) hydrogel for controlled drug delivery. Bull. Mater. Sci., 2011, 34(7), 1537-1547.
[http://dx.doi.org/10.1007/s12034-011-0356-1]
[20]
Food and D. Administration. Guidance for industry: Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Center for Drug Evaluation and Research; CDER, 2005, pp. 7-8.
[21]
Pandey, M.; Mohamad, N.; Amin, M.C. Bacterial cellulose/acrylamide pH-sensitive smart hydrogel: Development, characterization, and toxicity studies in ICR mice model. Mol. Pharm., 2014, 11(10), 3596-3608.
[http://dx.doi.org/10.1021/mp500337r] [PMID: 25157890]
[22]
Shah, A.; Hussain, I.; Murtaza, G. Chemical synthesis and characterization of chitosan/silver nanocomposites films and their potential antibacterial activity. Int. J. Biol. Macromol., 2018, 116, 520-529.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.05.057] [PMID: 29758310]
[23]
Khan, M.Z.U.; Makreski, P.; Murtaza, G. Preparation, optimization, in vitro evaluation and ex vivo permeation studies of finasteride loaded gel formulations prepared by using response surface methodology. Curr. Drug Deliv., 2018, 15(9), 1312-1322.
[http://dx.doi.org/10.2174/1567201815666180502165436] [PMID: 29732987]
[24]
Gatiganti, D.L.; Srimathkandala, M.H.; Ananthula, M.B.; Bakshi, V. Formulation and evaluation of oral natural polysaccharide hydrogel microbeads of irbesartan. Anal. Chem. Lett., 2016, 6(4), 334-344.
[http://dx.doi.org/10.1080/22297928.2016.1209427]
[25]
Anwar, H.; Ahmad, M.; Minhas, M.U.; Rehmani, S. Alginate-polyvinyl alcohol based interpenetrating polymer network for prolonged drug therapy, Optimization and in-vitro characterization. Carbohydr. Polym., 2017, 166, 183-194.
[http://dx.doi.org/10.1016/j.carbpol.2017.02.080] [PMID: 28385222]
[26]
Hua, S.; Wang, A. Synthesis, characterization and swelling behaviors of sodium alginate-g-poly (acrylic acid)/sodium humate superabsorbent. Carbohydr. Polym., 2009, i, 79-84.
[http://dx.doi.org/10.1016/j.carbpol.2008.06.013]
[27]
Minhas, M.U.; Ahmad, M.; Ali, L.; Sohail, M. Synthesis of chemically cross-linked polyvinyl alcohol-co-poly (methacrylic acid) hydrogels by copolymerization; A potential graft-polymeric carrier for oral delivery of 5-fluorouracil. Daru, 2013, 21(1), 44-51.
[http://dx.doi.org/10.1186/2008-2231-21-44] [PMID: 23721569]
[28]
Roxin, P.; Karlsson, A.; Singh, S.K. Characterization of cellulose acetate phthalate (CAP). Drug Dev. Ind. Pharm., 1998, 24(11), 1025-1041.
[http://dx.doi.org/10.3109/03639049809089946] [PMID: 9876557]
[29]
Shi, Y.; Liu, Z.; Yang, Y.; Xu, X.; Li, Y.; Li, T. Design of poly(mPEGMA-co-MAA) hydrogel-based mPEG-b-PCL nanoparticles for oral meloxicam delivery. Mater. Sci. Eng. C, 2017, 76, 975-984.
[http://dx.doi.org/10.1016/j.msec.2017.03.163] [PMID: 28482615]
[30]
Jalil, A.; Khan, S.; Naeem, F.; Haider, M.S.; Sarwar, S.; Riaz, A.; Ranjha, N.M. The structural, morphological and thermal properties of grafted pH-sensitive interpenetrating highly porous polymeric composites of sodium alginate/acrylic acid copolymers for controlled delivery of diclofenac potassium. Des. Monomers Polym., 2016, 20(1), 308-324.
[http://dx.doi.org/10.1080/15685551.2016.1259834] [PMID: 29491802]
[31]
Latha, K.; Srikanth, V.; Sunil, S.; Srinivasa, N.; Uhumwangho, M.; Shaik, N.; Murthy, K. Applicability of gum karaya in the preparation and in vitro evaluation of losartan potassium as chronotherapeutic drug delivery system. J. Sci. Res, 2015, 7(1-2), 65-74.
[http://dx.doi.org/10.3329/jsr.v7i1-2.21182]
[32]
Minhas, M.U.; Ahmad, M.; Khan, S.; Ali, L.; Sohail, M. Synthesis and characterization of β-cyclodextrin hydrogels: Crosslinked polymeric network for targeted delivery of 5-fluorouracil. Drug Deliv., 2016, 9, 10-18.
[33]
Ali, L.; Ahmad, M.; Usman, M. Evaluation of cross-linked hydroxypropyl methylcellulose graft-methacrylic acid copolymer as extended release oral drug carrier. Cellul. Chem. Technol., 2015, 49(2), 143-151.
[34]
Sohail, M.; Ahmad, M.; Minhas, M.U.; Ali, L.; Khalid, I.; Rashid, H. Controlled delivery of valsartan by cross-linked polymeric matrices: Synthesis, in vitro and in vivo evaluation. Int. J. Pharm., 2015, 487(1-2), 110-119.
[http://dx.doi.org/10.1016/j.ijpharm.2015.04.013] [PMID: 25865571]
[35]
Zhao, L.; Xu, L.; Mitomo, H.; Yashii, F. Synthesis of pH-sensitive PVP/CM-chitosan hydrogels with improved surface property by irradiation. Carbohydr. Polym., 2006, 64(3), 473-480.
[http://dx.doi.org/10.1016/j.carbpol.2005.12.014]
[36]
Mahdavinia, G.; Pourjavadi, A.; Hosseinzadeh, H.; Zohuriaan, M.J. Modified chitosan 4. Superabsorbent hydrogels from poly (acrylic acid-co-acrylamide) grafted chitosan with salt-and pH-responsiveness properties. Eur. Polym. J., 2004, 40(7), 1399-1407.
[http://dx.doi.org/10.1016/j.eurpolymj.2004.01.039]
[37]
Patil, J.; Mandave, S.; Jadhav, S. ionotropicaly crosslinked and chitosan reinforced losartan potassium loaded complex alginate beads: Design, characterization and evaluation. Malaya J. Biosci., 2014, 1(3), 126-133.
[38]
Elliott, J.E.; Anseth, J.W.; Bowman, C.N. Kinetic modeling of the effect of solvent concentration on primary cyclization during polymerization of multifunctional monomers. Chem. Eng. Sci., 2001, 56(10), 3173-3184.
[http://dx.doi.org/10.1016/S0009-2509(00)00547-9]
[39]
Elliott, J.E.; Macdonald, M.; Nie, J.; Bowman, C.N. Structure and swelling of poly (acrylic acid) hydrogels: Effect of pH, ionic strength, and dilution on the crosslinked polymer structure. Polym, 2004, 45(5), 1503-1510.
[http://dx.doi.org/10.1016/j.polymer.2003.12.040]
[40]
Rasool, F.; Ahmad, M.; Murtaza, G.; Khan, H.M.S.; Khan, S.A. Eudragit FS based colonic microparticls of metoprolol tartrate. Acta Pol. Pharm., 2012, 69(2), 347-353.
[PMID: 22568051]
[41]
Huang, Y.; Yu, H.; Xiao, C. pH-sensitive cationic guar gum/poly (acrylic acid) polyelectrolyte hydrogels: Swelling and in vitro drug release. Carbohydr. Polym., 2007, 69(4), 774-783.
[http://dx.doi.org/10.1016/j.carbpol.2007.02.016]
[42]
Sadeghi, M.; Hosseinzadeh, H. Synthesis and properties of biopolymer based on Gelatin-G-Poly (Sodium Acrylate-Co-Acrylamide) for cephalexin controlled release. Turk. J. Biochem., 2011, 36(4), 334-341.
[43]
Khalid, S.; Qadir, M.I.; Massud, A.; Ali, M.; Rasool, M.H. Effect of degree of cross-linking on swelling and drug release behaviour of poly (methyl methacrylate-co-itaconic acid)[P (MMA/IA)] hydrogels for site specific drug delivery. J. Drug Deliv. Sci. Technol., 2009, 19(6), 413-418.
[http://dx.doi.org/10.1016/S1773-2247(09)50085-8]
[44]
Khan, I.U.; Serra, C.A.; Anton, N.; Vandamme, T. Continuous-flow encapsulation of ketoprofen in copolymer microbeads via co-axial microfluidic device: Influence of operating and material parameters on drug carrier properties. Int. J. Pharm., 2013, 441(1-2), 809-817.
[http://dx.doi.org/10.1016/j.ijpharm.2012.12.024] [PMID: 23266758]
[45]
Furqan Muhammad, I.; Mahmood, A.; Aysha, R. Rashid. A. Synthesis and in vitro characterization of hydroxypropyl methylcellulose-graft-poly (acrylic acid/2-acrylamido-2-methyl-1-propanesulfonic acid) polymeric network for controlled release of captopril. Acta Pol. Pharm., 2016, 73(1), 183-196.
[PMID: 27008813]
[46]
Apu, A.S.; Pathan, A.H.; Shrestha, D.; Kibria, G.; Jalil, R.U. Investigation of in vitro release kinetics of carbamazepine from Eudragit® RS PO and RL PO matrix tablets. Trop. J. Pharm. Res., 2009, 8(2), 145-152.
[http://dx.doi.org/10.4314/tjpr.v8i2.44523]
[47]
Azizullah; Nisar-Ur-Rehman; Haider, A.; Kortz, U.; Afridi, S.; Sohail, M.; Joshi, S.A.; Iqbal, J. Novel pH responsive supramolecular hydrogels of chitosan hydrochloride and polyoxometalate: In-vitro, in-vivo and preliminary safety evaluation. Int. J. Pharm., 2017, 533(1), 125-137.
[http://dx.doi.org/10.1016/j.ijpharm.2017.09.034] [PMID: 28947244]
[48]
Barkat, K.; Ahmad, M.; Minhas, M.U.; Khalid, I. Oxaliplatin‐loaded crosslinked polymeric network of chondroitin sulfate-co-poly (methacrylic acid) for colorectal cancer: Its toxicological evaluation. J. Appl. Polym. Sci., 2017, 134(38), 45312-45320.
[http://dx.doi.org/10.1002/app.45312]