NANO-SPONGE NOVEL DRUG DELIVERY SYSTEM AS CARRIER OF ANTI-HYPERTENSIVE DRUG
DOI:
https://doi.org/10.22159/ijpps.2019v11i10.34812Keywords:
Cyclodextrins, Polymeric drug delivery system, Controlled release, Nanotechnology, Preclinical pharmacokinetics, CytotoxicityAbstract
Objective: The study was designed to prepare Nano-sponge formulation loaded with nifedipine. Studying parameters which affecting the formulas in addition to pharmacokinetics and toxicity tests.
Methods: Nine Nano-sponge formulations were prepared by the solvent evaporation technique. Different ratios of polymer ethylcellulose, CO-polymers β-cyclodextrin and hydroxypropyl β-cyclodextrin in addition to solubilizing agent polyvinyl alcohol were used. Thermal analysis, X-ray powder diffraction (XRPD), shape and surface morphology, particle size, %production yield, %porosity, % swelling, and % drug entrapment efficiency of Nano-sponge were examined. Release kinetic also studied beside comparison of pharmacokinetic parameters of the optimum choice formula and marketed one in addition to Toxicological consideration.
Results: Particle size in the range of 119.1 nm to 529 nm which were increased due to the increase in the concentration of polymer to the drug. Nano-sponge revealed porous, spherical nature. Increased in the drug/polymer molar ratios (1:1 to 1:3) may increase their % production yield ranged from 62.1% to 92.4%. The drug content of different formulations was in the range of 77.9% to 94.7%, and entrapment efficiency was in the range of 82.72 % to 96.63%. Drug released in controlled sustained pattern and followed Higuchi, s diffusion mechanism. Pharmacokinetic parameters of optimized formula showed significant higher maximum plasma drug concentration, area under plasma concentration-time curve, volume of distribution and mean residence time. Nano-sponge loaded drug proved biological safety at low concentrations.
Conclusion: Nano-sponge drug delivery system has showed small Nano size, porous with controlled drug release and significant-high plasma drug concentration that improved solubility, drug bioavailability and proved safety.
Downloads
References
Sharma R, Roderick B, Pathak K. Evaluation of kinetics and mechanism of drug release from Econazole nitrate Nanosponges loaded carbopol Hydrogel. Indian J Pharma Edu Res 2011;45 Suppl 1:25-31.
Meena KP, Dang JS, Samal PK, Namedo KP. Recent advances in microsphere manufacturing technology. Int J Pharm Technol 2011;3 Suppl 1:854-5.
Trotta F, Cavalli R, Tumiatti W, Zerbinati O, Rogero C, Vallero R. Ultrasound-assisted synthesis of cyclodextrin-based nanosponges. Eur Pharm 2013;1:786-841 B1.
Selvamuthukumar S, Anandam S, Kannan K, Manavalan R. Nanosponges. A novel class of drug delivery system-review. J Pharm Pharm Sci 2012;15 Suppl 1:103-11.
Rana Z, Gunjan A, Patil P, Zahid Z. Nanosponge–a completely new nano-horizon pharmaceutical applications and recent advances. Drug Dev Ind Pharm PMID 2012;22:585-681.
Swarupa A, Irafan K, Sharma JVC. Formulation and in vitro evaluation of β-cyclodextrin based nanosponges. Scholars Academic J Pharm 2017;6 Suppl 5:175-85.
Nacht S, Kantz M. The microsponge: a novel topical programmable delivery system. Top Drug Delivery Systems 2015;42:299-325.
Kilicarslan M, Baykara T. The effect of the drug/polymer ratio on the properties of verapamil HCl loaded microspheres. Int J Pharm 2003;252:99–109.
Maravajhala V, Papishetty S, Bandlapalli S. Nanotechnology in the development of drug delivery system. Int J Pharm Sci Res 2012;3 Suppl 1:41-9.
Ansari K, Torne S, Vavia PR, Trotta F, Cavalli R. Cyclodextrin-based nanosponges for delivery of resveratrol in vitro characterization, stability, cytotoxicity and permeation study. AAPS PharmSciTech 2011;12 Suppl 1:202-10.
Hardman JG, Limbird LE, Molinoft PB, Ruddon RW, Gilman AG. In: Goodman, Gilman (Eds.) The Pharmacological Basis of Therapeutics. 9th ed. Mcgraw Hill: New York; 1996. p. 635–6.
Miller RJ. Multiple calcium channels and neuronal function. Science 1987;235:46–52.
Kleinbloesem CH, Van Brummelen P, Faber H, Danhof M, Vermeulen NPE, Breimer DD. Biochem Pharmacol 1984;33:3721–4.
Ohkubo T, Noro H, Sngawara K. Novel drug delivery system nano-sponge as a carrier of an anti-hypertensive drug. J Pharm Biomed Anal 1992;10 Suppl 1:67-75.
Rajeswari C, Alka A, Javed A, Khar RK. Cyclodextrins in drug delivery: an update review. AAPS PharmSciTech 2005;6 Suppl 2:E329-57.
Ganesh Kumar J, Sreekanth D. Formulation development and evaluation of sustained release matrix tablets of vildagliptin-synthetic and natural polymers. Asian J Pharm 2015;9:2-9.
Amidon GE, Mudie DM. Developing solid oral dosage forms. 2nd ed. Science direct; 2017.
Raymond C Rowe, Paul J Sheskey, Marian E Quinn. Handbook of pharmaceutical excipients; pharmaceutical press and american pharmacists association; 2009. p. 641-3.
Lala R, Thorat A, Gargote C. Current trends in β-cyclodextrin based drug delivery systems. Int J Res Ayur Pharm 2011;2 Suppl 15:1520-6.
Shu XZ, Zhu KJ, Song W. Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure. Int J Pharm 2002;2:217-33.
Ghosh T, bharath S, Naik R, Basavaraj BV, Deveswaran R. Formulation and evaluation of buoyant tablets of ketoconazole. Int J Appl Pharm 2019;11 Suppl 2:18-23.
Hadjiioannou TP, Christian GD, Koupparis MA, Macheras PE. Quantitative calculations in pharmaceutical practice and research, VCH Publishers Inc, New York; 1993. p. 345-8.
Hisham H, Ibrahim AE, Elhenawee M. A novel stability-indicating HPLC-method for simultaneous determination of atenolol and nifedipine in presence of atenolol pharmacopeial impurities. J Appl Pharm Sci 2015;5 Suppl 8:17-25.
Awad Uday Y, Shravan Kumar P, Dinesh Kumar A, Bari Sandip. Estimation of nifedipine by reverse-phase high-performance liquid chromatography tablet dosage form. Int J Pharm Life Sci 2011;2 Suppl 3:610-2.
Shah SA, Savale SS, Rathod IS, Shishoo CJ. Development of a sensitive HPLC method for determination of plasma levels of nifedipine. Indian J Pharm Sci 1999;61:81-5.
Ahmed M, Ahmed T, Sultan RA, Murtaza G. Pharmacokinetic study of nifedipine in healthy adult male human volunteers. Topical J Pharm Res 2009;8 Suppl 5:385-91.
Kang J, Kumar V, Yang D, Chowdhury PR, Hohl RJ. Cyclodextrin complexation: influence on solubility, stability and cytotoxicity of camptothecin. Eur J Pharm Sci 2002;15:163–70.
Bulmus V, Woodward M, Lin L, Murthy N, Stayton P, Hoffman A. A new pH-responsive and glutathione-reactive, endosomal membrane-disruptive polymeric carrier for intracellular delivery of biomolecular drugs. J Controlled Release 2003;93:105-20.
Jiang J, Oberdo Rster G, Biswas P. Characterization of size, surface charge, and agglomeration state of nanoparticle dispersions for toxicological studies. J Nanopart Res 2009;11 Suppl 1:77−89.
Dubes A, Parrot Lopez H, Abdelwahed W, Degobert G, Fessi H, Shahgaldian P, et al. Scanning electron microscopy and atomic force microscopy imaging of solid lipid nanoparticles derivedfrom amphiphilic cyclodextrins. Eur J Pharm Biopharm 2003;55 Suppl 3:279–82.
Tansel C, Nursin G, Tamer B. Preparation and in vitro evaluation of modified release ketoprofen microsponges. II Farmaco 2003;58:101-6.
Mohammed Manna, Ahmed Abdel Bary, Mona El Assal, Fathy Abdullah. Formulation, optimization, and evaluation of solid dispersions of metformin HCl using factorial design. Int J Pharm Sci Rev Res 2016;41 Suppl 2:154-60.
Gurpreet Kaur, Geeta Aggarwal, Harikumar SL. Nanosponge: new colloidal drug delivery system for topical delivery. Indo Global J Pharm Sci 2015;5 Suppl 1:53-7.
Swaminathan S, Vavia PR, Trotta F, Torne S. Formulation of beta-cyclodextrin based nanosponges of itraconazole. J Incl Phenom Macrcycl Chem 2007;57(1 Suppl 4):89-94.
Corrigan OI, Healy AM, McDonald BF, Tajber L. Characterisation of excipient-free nanoporous microparticles (NPMPs) of bendroflumethiazide. Eur J Pharm Biopharm 2008;69:1182–6.
Barham AS, Corrigan OI, Lorraine MN, McDonald BF, Tajber L. Excipient-free nanoporous microparticles of budesonide for pulmonary delivery. Eur J Pharm Sci 2009;37:593–602.
Swaminathan S, Pastero L, Serpe L, Trotta F, Vavia P, Aquilano D, et al. Cyclodextrin-based nanosponges encapsulating camptothecin: physicochemical characterization, stability and cytotoxicity. Eur J Pharm Biopharm 2010;74:193–201.
Suthar V, Pratap A, Raval H. Studies on poly (hydroxy alkanoates)/(ethylcellulose) blends. Bull Mater Sci 2000; 23:215-9.
Shanker S, Linda P, Loredana S, Francesco T, Pradeep V, Dino A, et al. Cyclodextrin-based nanosponges encapsulating camptothecin: physicochemical characterization, stability and cytotoxicity. Eur J Pharm Biopharm 2010;74:193–201.
Wester R, Patel R, Natch S, Leyden J, Melendres J, Maibach H. Controlled release of benzoyl peroxide from a porous microsphere polymeric system can reduce topical irritancy. J Am Acad Derm 1991;24:720-6.
Rana Z, Gunjan P, Zahid Z. Nanosponges–a completely new nano-horizon: pharmaceutical applications and recent advances. Drug Dev Ind Pharm 2012;39:1-10.
Macheras P, Dokoumetzidis A. On the heterogeneity of drug dissolution and release. Pharm Res 2000;17:108-12.
Endrenyi L, Fritsch S, Yan W. Cmax/AUC is a clear measure than Cmax for absorption rates in an investigation of bioequivalence. Int J Clin Pharmacol Therapy Toxicol 1991;29 Suppl 10:394-9.
Yasmine Y, Caroline Jeba R. In vitro cytotoxicity activity of hydroalcoholic extract of polyherbal churnam (COFRI) in normal liver and kidney cell lines. Asian J Pharm Clin Res 2019;12 Suppl 3:74-7.
Prabhakaran D, Rajeshkanna A, Senthamilselvi MM. In vitro antioxidant and anti-inflamatory activity of the flower extract of opuntia stricta. Asian J Pharm Clin Res 2019;12 Suppl 3:208-12.
Published
How to Cite
Issue
Section
