DEVELOPMENT OF NANOPARTICLES SUSPENSION FOR PAEDIATRIC DRUG ADMINISTRATION
DOI:
https://doi.org/10.22159/ijpps.2022v14i2.43529Keywords:
Enalapril maleate, Nanoparticles suspension, Paediatric formulation, Taste masking, Eudragit RS 100, Tween 80Abstract
Objective: Enalapril maleate (EM) is an angiotensin-converting enzyme (ACE) inhibitor. It is generally prescribed for the treatment of hypertension, heart failure and chronic kidney diseases in adults and children. EM 2.5 mg, 5 mg, 10 mg and 20 mg tablets and EM injection 1.25 mg/ml are currently available in the market. But a liquid paediatric formulation of this medicine is not currently available. Also, it is a BCS class III drug, having a bioavailability of approximately 60%. The present study proposes a new strategy for improvement of drug bioavailability and taste masking: EM nanoencapsulation within polymeric nanoparticles suspensions prepared with Eudragit RS100 (ERS100) as polymer and Tween 80 as a stabilizer, aiming at obtaining a liquid dosage form suitable for paediatric administration.
Methods: Nanoprecipitation method used for the preparation of nanoparticles suspension. The preparations were evaluated for drug content, entrapment efficiency, particle size, zeta potential, polydispersity index, pH, viscosity and in vitro drug release. Based on the entrapment efficiency, viscosity and in vitro drug release the optimized formulation was selected. Optimized formulation evaluated for taste, ex vivo intestinal permeation, differential scanning calorimetry, scanning electron microscopy and release kinetic studies.
Results: The optimized nanoparticle formulation F8 having drug to polymer ratio of 1:100 showed satisfactory drug content (95.1%), entrapment efficiency (77.71%), particle size (198.47 nm), pH (6.36), viscosity (2.9 x〖10〗^(-3)Pa•s) and 81.2% drug release after 12 h. The formulation has taste-masking properties and shows 84.6% drug permeation through the goat intestine within 12 h.
Conclusion: The prepared nanoparticles suspension of Enalapril maleate was found to be an effective liquid pharmaceutical dosage form for paediatric administration with taste-masking properties.
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Ivanovska V, Rademaker CM, van Dijk L, Mantel-Teeuwisse AK. Pediatric drug formulations: a review of challenges and progress. Pediatrics. 2014;134(2):361-72. doi: 10.1542/peds.2013-3225, PMID 25022739.
Smeets NJL, Schreuder MF, Dalinghaus M, Male C, Lagler FB, Walsh J, Laer S, de Wildt SN. Pharmacology of enalapril in children: a review. Drug Discov Today. 2020 Aug 21;6446(20):30336-6. doi: 10.1016/j.drudis.2020.08.005, PMID 32835726.
Gomez HJ, Cirillo VJ, Irvin JD. Enalapril: a review of human pharmacology. Drugs. 1985;30Suppl 1:13-24. doi: 10.2165/00003495-198500301-00004, PMID 2994984.
Georgieva Y, Kassarova M, Kokova V, Apostolova E, Pilicheva B. Taste masking of enalapril maleate by microencapsulation in Eudragit EPO® microparticles. Pharmazie. 2020 Mar 20;75(2):61-9. doi: 10.1691/ph.2020.9123, PMID 32213236.
Georgieva YZ, Pilicheva BA, Kokova VY, Apostolova EG, Kassarova MI. Taste masking of enalapril maleate by the precipitation method. Folia Med (Plovdiv). 2019 Sep 30;61(3):426-34. doi: 10.3897/folmed.61.e39208, PMID 32337930.
Diefenthaeler HS, Bianchin MD, Marques MS, Nonnenmacher JL, Bender ET, Bender JG, Nery SF, Cichota LC, Kulkamp Guerreiro IC. Omeprazole nanoparticles suspension: development of a stable liquid formulation with a view to pediatric administration. International Journal of Pharmaceutics. 2020 Nov 15;589. doi: 10.1016/j.ijpharm.2020.119818, PMID 119818.
Krieser K, Emanuelli J, Daudt RM, Bilatto S, Willig JB, Guterres SS, Pohlmann AR, Buffon A, Correa DS, Kulkamp Guerreiro IC. Taste-masked nanoparticles containing saquinavir for paediatric oral administration. Mater Sci Eng C Maer Biol Appl. 2020 Dec;117. PMID 111315.
Patil N, Bhaskar R, Vyavhare V, Dhadge R, Khaire V, Patil Y. Overview on methods of synthesis of nanoparticles. Int J Curr Pharm Sci. 2020 Nov 5;15(2):11-6. doi: 10.22159/ijcpr.2021v13i2.41556.
D’Mello SR, Das SK, Das NG. Polymeric nanoparticles for small-molecule drugs: biodegradation of polymers and fabrication of nanoparticles. Drug Deli Nano Form Charact. 2006 Dec 16;61(3):45-52.
Hamid KM, Wais M, Sawant G. A review on nanoemulsions: formulation, composition, and applications. Asian J Pharm Clin Res. 2021 Apr 8;23(1):22-8. doi: 10.22159/ajpcr.2021.v14i4.40859.
Zielinska A, Carreiro F, Oliveira AM, Neves A, Pires B, Venkatesh DN, Durazzo A, Lucarini M, Eder P, Silva AM, Santini A, Souto EB. Polymeric nanoparticles: production, characterization, toxicology and ecotoxicology. Molecules. 2020 Jan;25(16):3731. doi: 10.3390/molecules25163731, PMID 32824172.
Raja MS, Venkataramana K. Formulation and evaluation of stabilized eprosartan nanosuspension. Int J App Pharm. 2020 Nov 6;12(6):83-7. doi: 10.22159/ijap.2020v12i6.39123.
Yellanki SK, Manoj A S, T M. Preparation and in vitro evaluation of metoprolol-loaded bovine serum albumin nanoparticles. Asian J Pharm Clin Res. 2021 Jan 5;14(1):213-7. doi: 10.22159/ajpcr.2021.v14i1.39738.
Senthilnathan B, Maheswaran A, Gopalasatheeskumar K, Masilamani K, Edros RZ. Formulation and evaluation of pregabalin-loaded eudragit S100 nanoparticles. IJETS. 2016 Dec 30;3(2):64-70. doi: 10.15282/ijets.6.2016.1.9.1059.
Balzus B, Sahle FF, Honzke S, Gerecke C, Schumacher F, Hedtrich S, Kleuser B, Bodmeier R. Formulation and ex vivo evaluation of polymeric nanoparticles for controlled delivery of corticosteroids to the skin and the corneal epithelium. Eur J Pharm Biopharm. 2017 Jun 1;115:122-30. doi: 10.1016/j.ejpb.2017.02.001, PMID 28189623.
Thoke SB, Gayke A, Dengale R, Patil P, Sharma Y. Review on: taste masking approaches and evaluation of taste masking. Int J Pharm Sci. 2012;4(2):1895-907.
Zervakis J, Graham BG, Schiffman SS. Taste effects of lingual application of cardiovascular medications. Physiol Behav. 2000 Jan 1;68(3):405-13. doi: 10.1016/s0031-9384(99)00208-5, PMID 10716552.
Liu W, Pan H, Zhang C, Zhao L, Zhao R, Zhu Y, Pan W. Developments in methods for measuring the intestinal absorption of nanoparticle-bound drugs. Int J Mol Sci. 2016 Jul 21;17(7):1171. doi: 10.3390/ijms17071171, PMID 27455239.
Punitha K, Kumar SS. Ex vivo permeability experiments in excised goat intestinal tissue and in vitro solubility enhancement of rosiglitazone by solid dispersion technique. J Pharm Resear. 2011 Jan;4(1):80-2.
Narade S, Pore Y. Optimization of ex vivo permeability characteristics of berberine in the presence of quercetin using 32 full factorial design. J App Pharm Sci. 2019 Jan;9(1):73-82. doi: 10.7324/JAPS.2019.90111.
Hina KS, Kshirsagar RV, Patil SG. Mathematical models for drug release characterization: a review. Wor J PharmSci. 2015;4(04):324-38.
Ramteke KH, Dighe PA, Kharat AR, Patil SV. Mathematical models of drug dissolution: a review. Sch Acad J Pharmacol. 2014;3(5):388-96.
Ray S, Mishra A, Mandal TK, Sa B, Chakraborty J. Optimization of the process parameters for the fabrication of a polymer-coated layered double hydroxide-methotrexate nanohybrid for the possible treatment of osteosarcoma. RSC Adv. 2015;5(124):102574-92. doi: 10.1039/C5RA15859A, PMID 102574.
Song X, Zhao Y, Hou S, Xu F, Zhao R, He J, Cai Z, Li Y, Chen Q. Dual agents loaded PLGA nanoparticles: the systematic study of particle size and drug entrapment efficiency. Eur J Pharm Biopharm. 2008 Jun 1;69(2):445-53. doi: 10.1016/ j.ejpb.2008.01.013, PMID 18374554.
Sukmawati A, Utami W, Yuliani R, Da’i M, Nafarin A. Effect of tween 80 on nanoparticle preparation of modified chitosan for targeted delivery of combination doxorubicin and curcumin analogue. IOP Conf Ser: Mater Sci Eng. 2018;311. doi: 10.1088/1757-899X/311/1/012024.
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