Evrim YENİLMEZ, A.Alper ÖZTÜRK, Umay Merve GÜVEN

Evaluation of carvedilol-loaded Eudragit®nanoparticles

The objective of present study was to prepare positively charged carvedilol-loaded nanoparticles providing a controlled release formulationby spray dryer techniqueand wasto examine the effect of different derivative of Eudragit®polymers on entrapment efficiency (EE%), dissolution profile andrelease kinetics. Two non-biodegradable positively charged polymers, Eudragit®RS100 and RL100 were used alone or in combination. The prepared formulations were evaluated for theirparticle size, polydispersity index, zeta potential,in vitrodissolution and in vitrorelease kinetics study.Particle sizes of placebo nanoparticlesand carvedilolloaded nanoparticles were 418.2±18.5/ 402.3±22.0/416.3±12.5 and 535.5±13.8/ 529.4±10.2/ 530.4±10.4 nm, respectively with PDI valuesof approximately 0.4–0.6 for each. Carvedilol loading was resulted in positive electrical charge on nanoparticles. The drug encapsulation efficiency was 68.45±4.67/ 63.58±2.30/ 65.67±4.21.In vitrocumulative release from the nanoparticles was 80-90 % at 48 hour.Morphology and solid state analyzes were performed also in nanoparticles. The results of this research indicate that spray dryer technique is suitable for carvedilol loaded Eudragit®nanoparticles and no burst effect but a prolonged drug release was observed from formulations.

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[1]Morgan T, clinical pharmacokinetics and pharmacodynamics of carvedilol. Clin Pharmacokinet. 1994; 26(5): 335-346.
[2]Ghassemi S, Haeri A, ShahhosseiniS, Dadashzadeh S, labrasol-enriched nanoliposomal formulation: novel approach to improve oral absorption of water-insoluble drug, carvedilol. AAPS PharmSciTech. 2018; 19(7): 2961-2970. [CrossRef]
[3]Kipriye Z, Şenel B, Yenilmez E, preparation and evaluation of carvedilol-loaded solid lipid nanoparticles for targeted drug delivery. Trop J Pharm Res. 2017; 16(9): 2057-2068. [CrossRef]
[4]Kajdič S, Vrečer F, Kocbek P, preparation of poloxamer-based nanofibers for enhanced dissolution of carvedilol. Eur J Pharm Sci. 2018; 117: 331-340. [CrossRef]
[5]Betala S, Varma MM, Abbulu K, formulation and evaluation of polymeric nanoparticles of an antihypetensive drug for gastroretention. Eur J Pharm Sci. 2018; 8(6): 82-86. [CrossRef]
[6]Devarajan PV, Sonavane GS, preparation and in vitro/in vivo evaluation of gliclazide loaded Eudragit®nanoparticles as a sustained release carrier. Drug Dev Ind Pharm. 2007; 33(2): 101-111. [CrossRef]
[7]Desai PP, Abhijit AD, Vandana BP,overcoming poor oral bioavailability using nanoparticle formulations–opportunities and limitations. Drug Discov Today Technol. 2012;9(2): e87-e95.
[8]Kumar N, Chaurasia S, Patel RR, Khan G, Kumar V,Mishra B,atorvastatin calcium encapsulated Eudragit® nanoparticles with enhanced oral bioavailability, safety and efficacy profile. Pharm Dev Technol. 2017; 22(2):156-167.
[9]Rieux A, Fievez V, Garinot M, Schneider YJ, Préat V,nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release. 2016;116(1):1-27.
[10]Singh G, Pai RS, atazanavir-loaded Eudragit®RL 100 nanoparticles to improve oral bioavailability: optimization and in vitro/in vivo appraisal. Drug Deliv. 2016; 23(2):532-539.
[11]Wang XQ, Zhang Q, pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs. Eur J Pharm Biopharm. 2012;82(2):219-229.
[12]Abdel-Wahhab MA, Joubert O, Khadrawy YA, Safar R, El-Nekeety AA, Ronzani C, Rihn BH,preliminary safety assessment of Eudragit®polymers nanoparticles administration in the rat brain. J Appl Pharm Sci. 2017; 7(07):176-185.
[13]Panda A, Meena J, Katara R, Majumdar DK,formulation and characterization of clozapine and risperidone co-entrapped spray-dried PLGA nanoparticles. Pharm Dev Technol. 2016;21(1):43-53.
[14]Harsha SN, Aldhubiab BE, Nair AB, Alhaider IA, Attimarad M, Venugopala KN,Asif AH,nanoparticle formulation by Büchi B-90 Nano Spray Dryer for oral mucoadhesion. Drug Des Devel Ther.2015; 9: 273. [CrossRef]
[15]Stocke NA, Meenach SA, Arnold SM, Mansour HM, Hilt JZ,formulation and characterization of inhalable magnetic nanocomposite microparticles (MnMs) for targeted pulmonary delivery via spray drying. Int J Pharm. 2015; 479(2):320-328.
[16]Cerchiara T, Abruzzo A, Di Cagno M, Bigucci F, Bauer-Brandl A, ParolinC, Luppi B, chitosan based micro-and nanoparticles for colon-targeted delivery of vancomycin prepared by alternative processing methods. Eur J Pharm Biopharm.2015; 92: 112-119.
[17]Güven UM, Berkman MS, Yazan Y, development and validation of uplc method for the determination of olopatadine hydrochloride in polymeric nanoparticles. Acta Pharm Sci. 2019; 57(1): 7-18.[CrossRef]
[18]Öztürk AA, Yenilmez E, Yazan Y,development and validation of high performance liquid chromatography (HPLC) modified method for dexketoprofen trometamol. Eur Int J Sci Tec. 2017;6(5):33-41.
[19]Öztürk AA, Güven UM, Yenilmez E,flurbiprofenloaded gel based topical delivery system: formulation and in vitro characterization with new developed uplc method. Acta Pharm Sci. 2018;56(4):81-105. [CrossRef]
[20]Öztürk AA, Yenilmez E, Yazan Y, dexketoprofen trometamol-loaded Eudragit®RL 100 nanoparticle formulation, characterization and release kinetics. Acta Pharm Sci. 2018; 57(1): 69-84. [CrossRef]
[21]Başaran E, GençerHK, Yenilmez E, Güven UM, voriconazole incorporated polymeric nanoparticles for ocular application. Lat Am J Phar. 36 (10): 1983-1994.
[22]Hasan AA, Sabry SA, Abdallah MH, El-damasy DA, formulation and in vitro characterization of poly (DL-lactide-co-glycolide)/Eudragit®RLPO or RS30D nanoparticles as an oral carrier of levofloxacin hemihydrate. Pharm Dev Technol. 2016; 21(6): 655-663.
[23]Öztürk AA, Gündüz AB, Özışık O,supervised machine learning algorithms for evaluation of solid lipid nanoparticles and particle size. Comb chem high throughput screen. 2018; 21(9): 693-699.
[24]Öztürk AA, Yenilmez E, Şenel B, Arslan R, Yazan Y,dexketoprofen trometamol-loaded Kollidon® SR and Eudragit® RS 100 polymeric nanoparticles: formulation and in vitro-in vivo evaluation. Lat Am J Pharm. 2017;36(11):2153-2165.
[25]Kumar N, Chaurasia S, Patel RR, Khan G, Kumar V, Mishra B, atorvastatin calcium encapsulated Eudragit®nanoparticles with enhanced oral bioavailability, safety and efficacy profile. Pharm Dev Technol. 2017; 22(2): 156-167.
[26]Dizaj SM, Lotfipour F, Barzegar-Jalali M, Zarrintan MH, Adibkia K, ciprofloxacin HCl-loaded calcium carbonate nanoparticles: preparation, solid state characterization, and evaluation of antimicrobial effect against staphylococcus aureus. Artif Cells Nanomed Biotechnol. 2017; 45(3): 535-543.
[27]Yenilmez E, desloratadine-Eudragit®RS100 nanoparticles: formulation and characterization. Turk J Pharm Sci. 2017; 14(2): 148-156.
[28]Younis N, Shaheen MA, Abdallah MH, silymarin-loaded Eudragit®RS100 nanoparticles improved the ability of silymarin to resolve hepatic fibrosis in bile duct ligated rats. Biomed Pharmacother. 2016; 81: 93–103.
[29]Guhagarkar SA, Shah D, Patel MD, Sathaye SS, Devarajan PV, polyethylene sebacate-silymarin nanoparticles with enhanced Hepatoprotective activity. J Nanosci Nanotechnol. 2015; 15(6): 4090–4093. [CrossRef]
[30]Kamba SA, Ismail M, Hussein-Al-Ali SH, Ibrahim TT, Zakaria ZB,in vitro delivery and controlled release of doxorubicin for targeting osteo-sarcoma bone cancer. Molecules.2013;18:10580–10598.
[31]Sahana D, Mittal G, Bhardwaj V, Kumar M,PLGA nanoparticles for oral delivery of hydrophobic drugs: Influence of organic solvent on nanoparticle formation and release behavior in vitro and in vivo using estradiol as a model drug. J Pharm Sci.2008;97:1530–1542.
[32]Güven UM,Yenilmez E,olopatadine hydrochloride loaded Kollidon®SR nanoparticles for ocular delivery: Nanosuspension formulation and in vitro–in vivo evaluation. J Drug Deliv Sci Technol. 2019; 51: 506-512.
[33]Öztürk AA, Güven UM, Yenı̇lmez E, Şenel B,effects of different derivatives of Eudragit polymer on entrapment efficiency, in vitro dissolution, release kinetics and cell viability results on extended release flurbiprofen loaded nanomedicines. Lat Am J Pharm. 2018;37(10):1981-1992.
[34]Ram AM, Raj PM, Kumar N, Raj R, comparative study of Eudragit RS 100 and RL 100 nanoparticles as ophthalmic vehicle for Fungal infection. Pharm Nanotechnol. 2016; 4(4): 316-328.
[35]JiaoY, UbrichN, Marchand-ArvierM, VigneronC, HoffmanM, LecompteT, MaincentP, in vitro and in vivo evaluation of oral heparin-loaded polymeric nanoparticles in rabbits.Circulation. 2002; 105:230-235.
[36]Hoffart V, Ubrich N, Lamprecht A, Bachelier K,Vigneron C, Lecompte T,Hoffman M, Maincent P, microencapsulation of low molecular weight heparin into polymeric particles designed with biodegradable and nonbiodegradable polycationic polymers. Drug Deliv 2002; 10:1–7.
[37]Bermejo M, Avdeef A, Ruiz A, Nalda R, Ruell JA, Tsinman O, González I, Fernández C, Sánchez G, Garrigues TM, Merino V, PAMPA—a drug absorption in vitro model 7. Comparing rat in situ, Caco-2, and PAMPA permeability of fluoroquinolones. Eur J Pharm Sci. 2004;21:429–41.
[38]Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, Xie S,DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. The AAPS J. 2010; 12: 263-271.
[39]Öztürk AA, Banderas LM, Otero MDC, Yenilmez E, Yazan Y,new approach to hypertension treatment: carvediol-loaded PLGA nanoparticles,preparation, in vitro characterization and gastrointestinal stability. Lat Am J Pharm. 2018; 37(9):1730-1741.
[40]Peppas NA, Sahlin JJ,a simple equation for the description of solute release. iii. coupling of diffusion and relaxation.Int J Pharm. 1989; 57(2):169-172.
[41]Siepmann J, Peppas NA,modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev. 2012; 64:163-174.
[42]Yang H, Li J, Patel S, Palmer KE, Devlin B, Rohan LC,design of poly(lactic-co-glycolic Acid) (PLGA) nanoparticles for vaginal co-delivery of griffithsin and dapivirine and their synergistic effect for HIV prophylaxis. Pharmaceutics. 2019; 11: 1-21.
[43]Öztürk AA, Banderas LM, Otero MDC, Yenilmez E, Şenel B, Yazan Y,dexketoprofen trometamol-loaded poly-pactic-co-glycolic Acid (PLGA) nanoparticles: preparation, in vitro characterization and cyctotoxity. Trop J Pharm Res. 2019; 18(1): 1-11. [CrossRef]
[44]ÖztürkAA, Çinar Nİ, Yenilmez E,development of nano-sized ketoprofen lysine incorporated Eudragit®S100 nanomedicine by double emulsion solvent evaporation and in vitro characterization. J Pharm Pharmacogn Res. 2019; 7(1): 47–58.[CrossRef