Generic placeholder image

Current Drug Delivery

Author(s): Pankaj Kumar Sharma*, Vikesh Kumar Shukla and Anoop Kumar

DOI: 10.2174/1567201818666210805153859

DownloadDownload PDF Flyer Cite As
Physical Characterization and In Vitro Evaluation of Dissolution Rate from Cefpodoxime Proxetil Loaded Self Solidifying Solid SNEDDS

Page: [395 - 406] Pages: 12

  • * (Excluding Mailing and Handling)

Abstract

Background: Cefpodoxime Proxetil (CPD) is a broad-spectrum cephalosporin indicated in respiratory and urinary tract infections. CPD is a BCS class IV drug with pH-dependent solubility and has poor bioavailability. This study investigated the challenges of developing ternary components based on solid SNEDDS of CPD for in vitro dissolution rate enhancement and self-solidifying behaviour.

Methods: Tween 80, Transcutol and PEG6000 were employed as surfactants, solvents and solidifiers for a base of ternary components to develop self-solidifying solid SNEDDS, respectively. Ternary phase diagrams were used to characterize solidifying behaviour of ternary components in different proportions. S-SNEDDS formulations were drawn on the solidification areas available in the phase diagram and characterized for IR, XRD, DSC and in vitro drug release in various pH media.

Results: Ternary components for the preparation of self-solidifying solid SNEDDS were selected based on drug solubility. FTIR and DSC characterization studies ruled out any drug interaction between CPD and components chosen to prepare S-SNEDDS. CPD was transformed from a crystalline into an amorphous state in ternary dispersions as revealed from XRD data. Optimized formulation (S-S 1) demonstrated more than 95% of drug release irrespective of the pH environments of the medium. Calculation of dissolution efficiency and similarity factors indicate that S SNEDDS resulted in a higher drug dissolution rate over binary dispersion (p<0.01). The stability studies showed that the S SNEDDS were stable in performances and CPD assay.

Conclusion: The present investigation provides an alternative approach for enhancing the CPD dissolution rate using self-solidifying solid SNEDDS exhibited solidification behaviour at ambient temperature conditions and drug loading, which could be exploited over conventional dosage form.

Keywords: Cefpodoxime proxetil, ternary dispersion, tween 80, polyethylene glycol 6000, transcutol, dissolution rate.

Graphical Abstract

[1]
Todd, W.M. Cefpodoxime proxetil: a comprehensive review. Int. J. Antimicrob. Agents, 1994, 4(1), 37-62.
[http://dx.doi.org/10.1016/0924-8579(94)90062-0] [PMID: 18611588]
[2]
Kakumanu, V.K.; Arora, V.; Bansal, A.K. Investigation of factors responsible for low oral bioavailability of cefpodoxime proxetil. Int. J. Pharm., 2006, 317(2), 155-160.
[http://dx.doi.org/10.1016/j.ijpharm.2006.03.004] [PMID: 16621365]
[3]
Nicolaos, G.; Crauste-Manciet, S.; Farinotti, R.; Brossard, D. Improvement of cefpodoxime proxetil oral absorption in rats by an oil-in-water submicron emulsion. Int. J. Pharm., 2003, 263(1-2), 165-171.
[http://dx.doi.org/10.1016/S0378-5173(03)00365-X] [PMID: 12954191]
[4]
Bajaj, A.; Rao, M.R.P.; Khole, I.; Munjapara, G. Self-nanoemulsifying drug delivery system of cefpodoxime proxetil containing tocopherol polyethylene glycol succinate. Drug Dev. Ind. Pharm., 2013, 39(5), 635-645.
[http://dx.doi.org/10.3109/03639045.2012.683440] [PMID: 22564007]
[5]
Gundogdu, E.; Koksal, C.; Karasulu, E. Comparison of cefpodoxime proxetil release and antimicrobial activity from tablet formulations: complexation with hydroxypropyl-β-cyclodextrin in the presence of water soluble polymer. Drug Dev. Ind. Pharm., 2012, 38(6), 689-696.
[http://dx.doi.org/10.3109/03639045.2011.621434] [PMID: 22010782]
[6]
Chu, J.; Li, G.; Row, K.H.; Kim, H.; Lee, Y.W. Preparation of cefpodoxime proxetil fine particles using supercritical fluids. Int. J. Pharm., 2009, 369(1-2), 85-91.
[http://dx.doi.org/10.1016/j.ijpharm.2008.10.029] [PMID: 19041383]
[7]
Khan, F.; Katara, R.; Ramteke, S. Enhancement of bioavailability of cefpodoxime proxetil using different polymeric microparticles. AAPS PharmSciTech, 2010, 11(3), 1368-1375.
[http://dx.doi.org/10.1208/s12249-010-9505-x] [PMID: 20821175]
[8]
Gao, Y.; Qian, S.; Zhang, J. Physicochemical and pharmacokinetic characterization of a spray-dried cefpodoxime proxetil nanosuspension. Chem. Pharm. Bull. (Tokyo), 2010, 58(7), 912-917.
[http://dx.doi.org/10.1248/cpb.58.912] [PMID: 20606336]
[9]
Bhargava, S.; Agrawal, G.P. Preparation & characterization of solid inclusion complex of cefpodoxime proxetil with beta-cyclodextrin. Curr. Drug Deliv., 2008, 5(1), 1-6.
[http://dx.doi.org/10.2174/156720108783330998] [PMID: 18220545]
[10]
Jain, S.K.; Shukla, M.; Shrivastava, V. Development and in vitro evaluation of ibuprofen mouth dissolving tablets using solid dispersion technique. Chem. Pharm. Bull. (Tokyo), 2010, 58(8), 1037-1042.
[http://dx.doi.org/10.1248/cpb.58.1037] [PMID: 20686256]
[11]
Koh, P.T.; Chuah, J.N.; Talekar, M.; Gorajana, A.; Garg, S. Formulation development and dissolution rate enhancement of efavirenz by solid dispersion systems. Indian J. Pharm. Sci., 2013, 75(3), 291-301.
[http://dx.doi.org/10.4103/0250-474X.117434] [PMID: 24082345]
[12]
Oh, D.H.; Park, Y.J.; Kang, J.H.; Yong, C.S.; Choi, H.G. Physicochemical characterization and in vivo evaluation of flurbiprofen-loaded solid dispersion without crystalline change. Drug Deliv., 2011, 18(1), 46-53.
[http://dx.doi.org/10.3109/10717544.2010.509365] [PMID: 20726805]
[13]
Liu, L.; Wang, X. Improved dissolution of oleanolic acid with ternary solid dispersions. AAPS PharmSciTech, 2007, 8(4), E113.
[http://dx.doi.org/10.1208/pt0804113] [PMID: 18181534]
[14]
Sharma, A.; Keservani, R.; Dadarwal, S.; Choudhary, Y.; Ramteke, S. Formulation and in vitro characterization of cefpodoxime proxetil gastroretentive microballoons. Daru, 2011, 19(1), 33-40.
[PMID: 22615637]
[15]
Patil, S.H.; Talele, G.S. Natural gum as mucoadhesive controlled release carriers: evaluation of cefpodoxime proxetil by D-optimal design technique. Drug Deliv., 2014, 21(2), 118-129.
[http://dx.doi.org/10.3109/10717544.2013.834416] [PMID: 24032629]
[16]
Date, A.A.; Nagarsenker, M.S. Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil. Int. J. Pharm., 2007, 329(1-2), 166-172.
[http://dx.doi.org/10.1016/j.ijpharm.2006.08.038] [PMID: 17010543]
[17]
Li, J.; Liu, P.; Liu, J.P.; Zhang, W.L.; Yang, J.K.; Fan, Y.Q. Novel Tanshinone II A ternary solid dispersion pellets prepared by a single-step technique: In vitro and in vivo evaluation. Eur. J. Pharm. Biopharm., 2012, 80(2), 426-432.
[http://dx.doi.org/10.1016/j.ejpb.2011.11.003] [PMID: 22119664]
[18]
Lee, S.N.; Poudel, B.K.; Tran, T.H.; Marasini, N.; Pradhan, R.; Lee, Y.I.; Lee, D.W.; Woo, J.S.; Choi, H.G.; Yong, C.S.; Kim, J.O. A novel surface-attached carvedilol solid dispersion with enhanced solubility and dissolution. Arch. Pharm. Res., 2013, 36(1), 79-85.
[http://dx.doi.org/10.1007/s12272-013-0008-7] [PMID: 23328872]
[19]
Okonogi, S.; Puttipipatkhachorn, S. Dissolution improvement of high drug-loaded solid dispersion. AAPS PharmSciTech, 2006, 7(2), E52.
[http://dx.doi.org/10.1208/pt070252] [PMID: 16796369]
[20]
Ghebremeskel, A.N.; Vemavarapu, C.; Lodaya, M. Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API: selection of polymer-surfactant combinations using solubility parameters and testing the processability. Int. J. Pharm., 2007, 328(2), 119-129.
[http://dx.doi.org/10.1016/j.ijpharm.2006.08.010] [PMID: 16968659]
[21]
Lovdahl, M.J.; Reher, K.E.; Russlie, H.Q.; Canafax, D.M. Determination of cefpodoxime levels in chinchilla middle ear fluid and plasma by high-performance liquid chromatography. J. Chromatogr. B Biomed. Appl., 1994, 653(2), 227-232.
[http://dx.doi.org/10.1016/0378-4347(93)E0420-U] [PMID: 8205250]
[22]
Cirri, M.; Maestrelli, F.; Corti, G.; Mura, P.; Valleri, M. Fast-dissolving tablets of glyburide based on ternary solid dispersions with PEG 6000 and surfactants. Drug Deliv., 2007, 14(4), 247-255.
[http://dx.doi.org/10.1080/10717540601067802] [PMID: 17497357]
[23]
Lim, H.T.; Balakrishnan, P.; Oh, D.H.; Joe, K.H.; Kim, Y.R.; Hwang, D.H.; Lee, Y.B.; Yong, C.S.; Choi, H.G. Development of novel sibutramine base-loaded solid dispersion with gelatin and HPMC: physicochemical characterization and pharmacokinetics in beagle dogs. Int. J. Pharm., 2010, 397(1-2), 225-230.
[http://dx.doi.org/10.1016/j.ijpharm.2010.07.013] [PMID: 20637849]
[24]
Quan, Q.; Kim, D.W.; Marasini, N.; Kim, D.H.; Kim, J.K.; Kim, J.O.; Yong, C.S.; Choi, H.G. Physicochemical characterization and in vivo evaluation of solid self-nanoemulsifying drug delivery system for oral administration of docetaxel. J. Microencapsul., 2013, 30(4), 307-314.
[http://dx.doi.org/10.3109/02652048.2012.726280] [PMID: 23101936]
[25]
Caon, T.; Konig, R.A.; da Cruz, A.C.; Cardoso, S.G.; Campos, C.E.; Cuffini, S.L.; Koester, L.S.; Simões, C.M. Development and physicochemical characterization of saquinavir mesylate solid dispersions using Gelucire 44/14 or PEG 4000 as carrier. Arch. Pharm. Res., 2013, 36(9), 1113-1125.
[http://dx.doi.org/10.1007/s12272-013-0142-2] [PMID: 23700292]
[26]
Morris, K.R.; Knipp, G.T.; Serajuddin, A.T. Structural properties of polyethylene glycol-polysorbate 80 mixture, a solid dispersion vehicle. J. Pharm. Sci., 1992, 81(12), 1185-1188.
[http://dx.doi.org/10.1002/jps.2600811212] [PMID: 1491337]
[27]
Mitali, K.; Gopal, S.N.; Wah, T.Y.; Lin, L. Ternary dispersions to enhance solubility of poorly soluble antioxidants. Colloids Surf., 2013, A433, 111-121.
[28]
Pathak, D.; Dahiya, S.; Pathak, K. Solid dispersion of meloxicam: factorially designed dosage form for geriatric population. Acta Pharm., 2008, 58(1), 99-110.
[http://dx.doi.org/10.2478/v10007-007-0048-y] [PMID: 18337211]
[29]
Sakeer, K.; Al-Zein, H.; Hassan, I.; Desai, S.; Nokhodchi, A. Enhancement of dissolution of nystatin from buccoadhesive tablets containing various surfactants and a solid dispersion formulation. Arch. Pharm. Res., 2010, 33(11), 1771-1779.
[http://dx.doi.org/10.1007/s12272-010-1109-1] [PMID: 21116780]
[30]
Ghebremeskel, A.N.; Vemavarapu, C.; Lodaya, M. Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API: stability testing of selected solid dispersions. Pharm. Res., 2006, 23(8), 1928-1936.
[http://dx.doi.org/10.1007/s11095-006-9034-1] [PMID: 16871443]
[31]
Elkasabgy, N.A. Ocular supersaturated self-nanoemulsifying drug delivery systems (S-SNEDDS) to enhance econazole nitrate bioavailability. Int. J. Pharm., 2014, 460(1-2), 33-44.
[http://dx.doi.org/10.1016/j.ijpharm.2013.10.044] [PMID: 24184217]
[32]
Inugala, S.; Eedara, B.B.; Sunkavalli, S.; Dhurke, R.; Kandadi, P.; Jukanti, R.; Bandari, S. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of darunavir for improved dissolution and oral bioavailability: In vitro and in vivo evaluation. Eur. J. Pharm. Sci., 2015, 74, 1-10.
[http://dx.doi.org/10.1016/j.ejps.2015.03.024] [PMID: 25845633]
[33]
Nasr, A.; Gardouh, A.; Ghorab, M. Novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of olmesartan medoxomil: Design, formulation, pharmacokinetic and bioavailability evaluation. Pharmaceutics, 2016, 8(3), 20-49.
[http://dx.doi.org/10.3390/pharmaceutics8030020] [PMID: 27355963]
[34]
Patel, A.; Shelat, P.; Lalwani, A. Development and optimization of solid self nanoemulsifying drug delivery (S-SNEDDS) using D-optimal design for improvement of oral bioavailability of amiodarone hydrochloride. Curr. Drug Deliv., 2015, 12(6), 745-760.
[http://dx.doi.org/10.2174/1567201812666150302122501] [PMID: 25731867]
[35]
Reddy, M.S.; Sowjanya, N. Formulation and in vitro characterization of solid self-nanoemulsifying drug delivery system (S-SNEDDS) of Simvastatin. J. Pharm. Sci. Res., 2015, 7, 40-48.
[36]
Alwadei, M.; Kazi, M.; Alanazi, F.K. Novel oral dosage regimen based on self-nanoemulsifying drug delivery systems for codelivery of phytochemicals - Curcumin and thymoquinone. Saudi Pharm. J., 2019, 27(6), 866-876.
[http://dx.doi.org/10.1016/j.jsps.2019.05.008] [PMID: 31516329]
[37]
Buya, A.B.; Ucakar, B.; Beloqui, A.; Memvanga, P.B.; Préat, V. Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDSs) for senicapoc. Int. J. Pharm., 2020, 580, 119180.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119180] [PMID: 32135227]
[38]
Baloch, J.; Sohail, M.F.; Sarwar, H.S.; Kiani, M.H.; Khan, G.M.; Jahan, S.; Rafay, M.; Chaudhry, M.T.; Yasinzai, M.; Shahnaz, G. Self-nanoemulsifying drug delivery system (SNEDDS) for improved oral bioavailability of chlorpromazine: In vitro and in vivo evaluation. Medicina (Kaunas), 2019, 55(5), 210-223.
[http://dx.doi.org/10.3390/medicina55050210] [PMID: 31137751]
[39]
Bravo-Alfaroa, D.A.; Muñoz-Correa, M.O.F.; Santos-Luna, D.; Toro-Vazquezb, J.F.; Cano-Sarmientoc, C.; García-Varelad, R.; Garcia, H.S. Encapsulation of an insulin-modified phosphatidylcholine complex in a self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin delivery. Pharma Excipients, 2020, 57, 101622.
[http://dx.doi.org/10.1016/j.jddst.2020.101622]
[40]
Alghananim, A.; Özalp, Y.; Mesut, B.; Serakinci, N.; Özsoy, Y.; Güngör, S. A solid ultra fine self-nanoemulsifying drug delivery system (S-SNEDDS) of deferasirox for improved solubility: optimization, characterization, and in vitro cytotoxicity studies. Pharmaceuticals (Basel), 2020, 13(8), 162.
[http://dx.doi.org/10.3390/ph13080162] [PMID: 32722238]
[41]
Venkatesh, M.; Mallesh, K. Self-nano emulsifying drug delivery system (SNEDDS) for oral delivery of atorvastatin- formulation and bioavailability studies. J. D. Del. Ther., 2013, 3(3), 131-142.
[http://dx.doi.org/10.22270/jddt.v3i3.517]
[42]
Yasser, M.; Gad, S.; El-sayed, M.; Ghorab, M. The effect of converting liquid valsartan SNEDDS into solid SNEDDS using different solid carriers on its performance. Int. J. Bio. Pharm. Res., 2013, 4(12), 1015-1026.
[43]
Wang, Q.; Guo, M.; Adu-Frimpong, M.; Zhang, K.; Yang, Q.; Toreniyazov, E.; Ji, H.; Xu, X.; Cao, X.; Yu, J. Self-micro-emulsifying controlled release of eugenol pellets: preparation, in vitro/in vivo investigation in beagle dogs. AAPS PharmSciTech, 2019, 20(7), 284.
[http://dx.doi.org/10.1208/s12249-019-1499-4] [PMID: 31407165]
[44]
Rao, S.V.R.; Shao, J. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs: I. Formulation development. Int. J. Pharm., 2008, 362(1-2), 2-9.
[http://dx.doi.org/10.1016/j.ijpharm.2008.05.018] [PMID: 18650038]
[45]
Dondapati, D.; Srimathkandala, M.H.; Sanka, K.; Bakshi, V. Improved solubility and dissolution release profile of lurasidone by solid self-nanoemulsifying drug delivery system. Anal. Chem. Lett., 2016, 6(2), 86-97.
[http://dx.doi.org/10.1080/22297928.2016.1164075]