FACTORIAL DESIGN AS THE METHOD IN THE OPTIMIZATION OF TIMOLOL MALEATE-LOADED NANOPARTICLE PREPARED BY IONIC GELATION TECHNIQUE

  • WILDAN KHAIRI MUHTADI Departement of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, D. I. Yogyakarta 55281, Indonesia
  • LARAS NOVITASARI Departement of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, D. I. Yogyakarta 55281, Indonesia
  • RONNY MARTIEN Departement of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, D. I. Yogyakarta 55281, Indonesia
  • RETNO DANARTI Department of Dermatology and Venereology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Farmako Sekip Utara, D. I. Yogyakarta 55281, Indonesia

Abstract

Objective: This study aims to optimize the timolol maleate (TM) nanoparticle prepared by ionic gelation method using the factors of pectin (PC), calcium chloride (CC), and chitosan (CS) concentrations with the responses of entrapment efficiency, particle size, and polydispersity index using 23 factorial design.


Methods: TM nanoparticle suspensions were obtained by mixing of PC (0,4-0,6% (w/v)), CC (0,2-0,4% (w/v)), and CS (0,01-0,02% (w/v)) with TM concentration of 0,02% w/v. Each mixture was then tested for entrapment efficiency, particle size, and polydispersity index. The test results were analyzed with 23 factorial design using Design-Expert software in order to determine the optimum formula.


Results: The optimization study showed that all of the factors influenced the responses significantly (p<0.05) based on the analysis of variance (ANOVA) of the suggested models. The R2value and the adequate precision value of the three models were more than 0.7 and 4, respectively. The difference between Adjusted R-Squared and Predicted R-Squared value were less than 0.200. The optimum condition of TM nanoparticle was suggested at the desirability value of 0.839 with the concentration of PC, CC, and CS of 0,4% (w/v), 0,2% (w/v), and 0,01% (w/v), respectively. The entrapment efficiency, particle size, and polydispersity index of the optimum condition were 24.791±2.84%, 274.867±14.45 nm, and 0.634±0.066, respectively.


Conclusion: The 23factorial design has been proved as the suitable method to determine the optimum condition that yields the good results of the entrapment efficiency, particle size, and polydispersity index of the TM-loaded nanoparticle prepared by ionic gelation method.

Keywords: Nanoparticle, Ionic gelation, Timolol maleate, Pectin, Calcium chloride, Chitosan, Factorial design

References

1. Danarti R, Ariwibowo L, Radiono S, Budiyanto A. Topical timolol maleate 0.5% for infantile hemangioma: its effectiveness compared to ultrapotent topical corticosteroids-a single-center experience of 278 cases. Dermatology (Basel) 2016;232:566–71.
2. Zheng JW, Zhang L, Zhou Q, Mai HM, Wang YA, Fan XD, et al. A practical guide to treatment of infantile hemangiomas of the head and neck. Int J Clin Exp Med 2013;6:851–60.
3. Frommelt P, Juern A, Siegel D, Holland K, Seefeldt M, Yu J, et al. Adverse events in young and preterm infants receiving topical timolol for infantile hemangioma. Pediatr Dermatol 2016; 33:405–14.
4. Zhang Z, Tsai PC, Ramezanli T, Michniak Kohn BB. Polymeric nanoparticles-based topical delivery systems for the treatment of dermatological diseases. Wiley Interdiscip Rev: Nanomed Nanobiotechnol 2013;5:205–18.
5. Kunjachan S, Jose S, Lammers T. Understanding the mechanism of ionic gelation for the synthesis of chitosan nanoparticles using qualitative techniques. Asian J Pharm 2014;4:148-53.
6. Grabnar PA, Kristl J. The manufacturing techniques of drug-loaded polymeric nanoparticles from preformed polymers. J Microencapsul 2011;28:323-35.
7. Nagpal K, Singh SK, Mishra DN. Chitosan nanoparticles: a promising system in novel drug delivery. Chem Pharm Bull 2010;58:1423-30.
8. Grabnar PA, Kristl J. Physicochemical characterization of protein-loaded pectin-chitosan nanoparticles prepared by polyelectrolyte complexation. Pharmazie 2010;65:851-2.
9. de Pinho Neves AL, Milioli CC, Müller L, Riella HG, Kuhnen NC, Stulzer HK. Factorial design as a tool in chitosan nanoparticles development by ionic gelation technique. Colloids Surf A 2014;445:34-9.
10. Ilka R, Mohseni M, Kianirad M, Naseripour M, Ashtari K, Mehravi B. Nanogel-based natural polymers as smart carriers for the controlled delivery of timolol maleate through the cornea for glaucoma. Int J Biol Macromol 2018;109:955-62.
11. Siafaka PI, Titopoulou A, Koukaras EN, Kostoglou M, Koutris E, Karavas E, et al. Chitosan derivatives as effective nanocarriers for ocular release of timolol drug. Int J Pharm 2015;495:249–64.
12. Shaw R, Festing MFW, Peers I, Furlong L. Use of factorial designs to optimize animal experiments and reduce animal use. ILAR J 2002;43:223-32.
13. Bhoskar M, Patil P. Development and evaluation of paclitaxel loaded nanoparticles using 24 factorial design. Int J Curr Pharm Res 2015;7:64-72.
14. Jain A, Jain SK. Formulation and optimization of temozolomide nanoparticles by 3 factors 2 level factorial design. Biomatter 2013;3:1-13.
15. Pham DT, Saelim N, Tiyaboonchai W. Design of experiments model for the optimization of silk fibroin based nanoparticle. Int J Appl Pharm 2018;10:195-201.
16. Shiyan S, Hertiani T, Martien R, Nugroho AK. Optimization of a novel kinetic-assisted infundation of white tea (Camellia sinensis) using central composite design. Int J Appl Pharm 2018;10:259-67.
17. Setyawan EI, Setyowati EP, Rohman A, Nugroho AK. Central composite design for optimizing the extraction of EGCG from green tea leaf (Camellia sinensis L.). Int J Appl Pharm 2018;10:211–6.
18. Pawar AP, Gadhe AR, Venkatachalam P, Sher P, Mahadik KR. Effect of core and surface cross-linking on the entrapment of metronidazole in pectin beads. Acta Pharm 2008;58:78–85.
19. Sharma R, Ahuja M, Kaur H. Thiolated pectin nanoparticles: preparation, characterization and ex vivo corneal permeation study. Carbohydr Polym 2012;87:1606–10.
20. Opanasopit P, Apirakaramwong A, Ngawhirunpat T, Rojanarata T, Ruktanonchai U. Development and characterization of pectinate micro/nanoparticles for gene delivery. AAPS PharmSciTech 2008;9:67–74.
21. Zaki SSO, Ibrahim MN, Katas H. Particle size affects concentration-dependent cytotoxicity of chitosan nanoparticles towards mouse hematopoietic stem cells. J Nanotechnol 2015. http://dx.doi.org/10.1155/2015/919658
22. Maciel VBV, Yoshida CMP, Pereira SMSS, Goycoolea FM, Franco TT. Electrostatic self-assembled chitosan-pectin nano-and microparticles for insulin delivery. Molecules 2017;22:1-21.
23. Melo NFS, Campos EVR, Paula ED, Rosa AH, Fraceto LF. Factorial design and characterization studies for articaine hydrochloride loaded alginate/chitosan nanoparticles. J Colloid Sci Biotechnol 2013;2:146–52.
24. Masarudin MJ, Cutts SM, Evison BJ, Phillips DR, Pigram PJ. Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of 14C-doxorubicin. Nanotechnol Sci Appl 2015;8:67-80.
25. Candioti LV, De Zan MM, Camara MS, Goicoechea HC. Experimental design and multiple response optimization. Using the desirability function in analytical methods development. Talanta 2014;124:123-38.
26. Abdalla KA, Kamoun EA, Maghraby GME. Optimization of the entrapment efficiency and release of ambroxol hydrochloride alginate beads. J Appl Pharm Sci 2015;5:13-9.
27. Poland CA, Read SAK, Varet J, Carse G, Christensen FM, Hankin SM. Dermal absorption of nanomaterials part of the ”Better control of nano” initiative 2012-2015. Denmark: The Danish Environmental Protection Agency; 2013.
28. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018;10:57.
29. Zayed GM, El-feky GS. Growth factor loaded functionalized gold nanoparticles as a potential targeted treatment for acute renal failure. Int J Appl Pharm 2019;11:174–85.
Statistics
209 Views | 54 Downloads
Citatons
How to Cite
MUHTADI, W. K., NOVITASARI, L., MARTIEN, R., & DANARTI, R. (2019). FACTORIAL DESIGN AS THE METHOD IN THE OPTIMIZATION OF TIMOLOL MALEATE-LOADED NANOPARTICLE PREPARED BY IONIC GELATION TECHNIQUE. International Journal of Applied Pharmaceutics, 11(5), 66-70. https://doi.org/10.22159/ijap.2019v11i5.34435
Section
Original Article(s)