CENTRAL COMPOSITE FACE-CENTERED DESIGN-BASED OPTIMISATION, DEVELOPMENT AND CHARACTERISATION OF FAVIPIRAVIR-LOADED PLGA NANOPARTICLES

##article.authors##

  • VENKATA KAVYA R Department of Pharmaceutics, Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh, India https://orcid.org/0000-0002-3253-0781
  • JEEVANA JYOTHI B. Department of Pharmaceutics, Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh, India https://orcid.org/0000-0002-8954-2409

##semicolon##

Favipiravir##common.commaListSeparator## PLGA##common.commaListSeparator## Central composite design

##article.abstract##

Objective: The objective of this study is to fabricate favipiravir-loaded PLGA nanoparticulate systems that can increase the solubility along with the sustained release of favipiravir.

Methods: The favipiravir-loaded Poly (D, L-lactic-co-glycolide) (PLGA) nanoparticulate systems were prepared by the nanoprecipitation method. A 3-factor, 2-level central composite face-centered design was employed to study the effect of formulation variables having a concentration of PLGA, polyvinyl alcohol (PVA) and stirring rate as critical formulation attributes and particle size, drug entrapment efficiency, and percentage cumulative drug release as critical quality attributes on prepared favipiravir nanoparticles. Drug interaction studies were performed by FTIR and DSC. Surface morphology was analysed by scanning electron microscopy (FEI Quanta 250 FEG, USA). Particle size, zeta potential, and polydispersity index were analysed by the nanoparticle analyser SZ-100 (HORIBA Scientific nanopartica, Japan). In vitro drug release studies were performed using a UV-Visible spectrophotometer at λmax 234 nm. In vitro drug release data obtained was fitted into various mathematical kinetic models.

Results: The numerical optimization process predicted the level of PLGA concentration as 69.96 mg, PVA concentration as 4.99%, and stirring rate as 799 rpm for the optimised formulation. The low percentage of relative error for the optimised formulation confirms the validation of the model. The optimised formulation had a 77.65% entrapment efficiency with a particle size of 109.7 nm and the percent cumulative drug release showed 86.46% drug release over 720 min. The drug release was found to follow first-order release kinetics with anomalous non-Fickian diffusion kinetics.

Conclusion: Hence, such an attempt at fabrication of favipiravir-loaded PLGA nanoparticulate systems may be useful for sustained release of drug over 720 min.

##submission.citations##

Joshi S, Parkar J, Ansari A, Vora A, Talwar D, Tiwaskar M. Role of favipiravir in the treatment of COVID-19. Int J Infect Dis. 2021;102:501-8. doi: 10.1016/j.ijid.2020.10.069. PMID 33130203.

Chen R, Wang T, Song J, Pu D, He D, Li J. Antiviral drug delivery system for enhanced bioactivity, better metabolism and pharmacokinetic characteristics. Int J Nanomedicine. 2021;16:4959-84. doi: 10.2147/IJN.S315705. PMID 34326637.

Łagocka R, Dziedziejko V, Kłos P, Pawlik A. Favipiravir in therapy of viral infections. J Clin Med. 2021;10(2):273-89. doi: 10.3390/jcm10020273, PMID 33451007.

Pathak S, Vyas SP, Pandey A. Development, characterization and in vitro release kinetic studies of ibandronate loaded chitosan nanoparticles for effective management of osteoporosis. Int J App Pharm. 2021;13(6):120-5. doi: 10.22159/ijap.2021v13i6.42697.

Faridi Esfanjani A, Jafari SM. Biopolymer nanoparticles and natural nano-carriers for nano-encapsulation of phenolic compounds. Colloids Surf B Biointerfaces. 2016;146:532-43. doi: 10.1016/j.colsurfb.2016.06.053. PMID 27419648.

Bohrey S, Chourasiya V, Pandey A. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in vitro drug release and release kinetic study. Nano Converg. 2016;3(1):3. doi: 10.1186/s40580-016-0061-2, PMID 28191413.

Tripathi SK, Patel B, Shukla S, Pachouri C, Pathak S, Pandey A. Donepezil loaded PLGA nanoparticles, from modified nano-precipitation, an advanced drug delivery system to treat alzheimer disease. J Phys: Conf Ser. 2021;1849(1):012001. doi: 10.1088/1742-6596/1849/1/012001.

Tulbah AS, Hin Lee WH. Physicochemical characteristics and in vitro toxicity/anti-SARS-CoV-2 activity of favipiravir solid lipid nanoparticles (SLNs). Pharmaceuticals (Basel). 2021;14(10):1059-72. doi: 10.3390/ph14101059, PMID 34681283.

Yao Chunchun, Xiang F, Xu Zhangyi. Metal oxide nanocage as drug delivery systems for favipiravir, as an effective drug for the treatment of COVID-19: a computational study. J Mol Model. 2022;28(3):64. doi: 10.1007/s00894-022-05054-6, PMID 35182223.

Shaik NB, Pk L, Vv BR. Formulation and evaluation of favipiravir proliposomal powder for pulmonary delivery by nebulization. Int J Pharm Res Allied Sci 2022;11(2):36-44. doi: 10.51847/4McfhPccXs.

Avinash D, Gudipati M, Ramana MV, Vadlamudi P, Nadendla RR. Mouth dissolving tablets of favipiravir using superdisintegrants: preparation, optimization and in vitro evaluation. JPRI 2021;33:28-39. doi: 10.9734/jpri/2021/v33i631187.

Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Preat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Release. 2012;161(2):505-22. doi: 10.1016/j.jconrel.2012.01.043. PMID 22353619.

Venkatesh DN, Baskaran M, Karri VV, Mannemala SS, Radhakrishna K, Goti S. Fabrication and in vivo evaluation of nelfinavir loaded PLGA nanoparticles for enhancing oral bioavailability and therapeutic effect. Saudi Pharm J. 2015;23(6):667-74. doi: 10.1016/j.jsps.2015.02.021. PMID 26702262.

Yadav KS, Sawant KK. Modified nanoprecipitation method for preparation of cytarabine-loaded PLGA Nanoparticles. AAPS PharmSciTech. 2010;11(3):1456-65. doi: 10.1208/s12249-010-9519-4, PMID 20842542.

Todaro B, Moscardini A, Luin S. Pioglitazone-loaded PLGA nanoparticles: towards the most reliable synthesis method. Int J Mol Sci. 2022;23(5):2522-6. doi: 10.3390/ijms23052522, PMID 35269665.

Sebastian G, Priya S, P James, MA Sannidhi, Prabhu VK, Sannidhi, Vinay Kiran Prabhu. Computational tools assisted formulation optimization of nebivolol hydrochloride loaded PLGA nanoparticles by 32factorial designs. Int J App Pharm. 2022;14(4):251-8. doi: 10.22159/ijap.2022v14i4.44865.

Saka OM, Oz UC, Kucukturkmen B, Devrim B, Bozkır A. Central composite design for optimization of zoledronic acid loaded PLGA nanoparticles. J Pharm Innov. 2020;15(1):3-14. doi: 10.1007/s12247-018-9365-6.

Varshosaz J, Ghaffari S, Khoshayand MR, Atyabi F, Azarmi S, Kobarfard F. Development and optimization of solid lipid nanoparticles of amikacin by central composite design. J Liposome Res. 2010;20(2):97-104. doi: 10.3109/08982100903103904, PMID 19621981.

Panda BP. Impact of Statistical Central Composite Face Centered Design Approach on Method and Process Optimization of Metformin Hydrochloride Loaded PLGA Nanoformulation. Micro Nanosystems. 2017;9(1):55-71. doi: 10.2174/1876402909666170817113542.

mali S, oza N. Central composite design for formulation and optimization of long-acting injectable (LAI) microspheres of paliperidone palmitate. Int J App Pharm. 2021;13(5):87-98. doi: 10.22159/ijap.2021v13i5.42297.

Hassan H, Adam SitiK, Alias E, Meor Mohd Affandi MMR, Shamsuddin AF, Basir R. Central composite design for formulation and optimization of solid lipid nanoparticles to enhance oral bioavailability of acyclovir. Molecules. 2021;26(18):5432. doi: 10.3390/molecules26185432, PMID 34576904.

Yadav M, Aggarwal P, Yadav D, Singh A. Formulation and evaluation of clobetasol-17-propionate-loaded carboxymethyl chitosan nanoparticle. Asian J Pharm Clin Res. 2022;2022:88-93. doi: 10.22159/ajpcr.2022.v15i9.45743.

Tığlı Aydın RS, Kaynak G, Gumusderelioglu M. Salinomycin encapsulated nanoparticles as a targeting vehicle for glioblastoma cells. J Biomed Mater Res A. 2016;104(2):455-64. doi: 10.1002/jbm.a.35591. PMID 26476239.

Naveentaj S, Muzib YI, Radha R. Design and development of simvastatin-loaded pharmacosomes to enhance transdermal permeation. Int J App Pharm. 2022;14(4):148-57. doi: 10.22159/ijap.2022v14i4.44527.

Salmanpour M, Saeed Vaghefi M, Abolmaali SS, Tamaddon AM. Sterically stabilized polyionic complex nanogels of chitosan lysate and PEG-b-Polyglutamic acid copolymer for the delivery of active irinotecan metabolite (SN-38). Curr Drug Deliv. 2021;18(6):741-52. doi: 10.2174/1567201817999201103195846, PMID 33155910.

Yang H, Li J, Patel SK, 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(4):184. doi: 10.3390/pharmaceutics11040184, PMID 30995761.

Avinash D, Gudipati M, Ramana MV, Vadlamudi P, Nadendla RR. Mouth dissolving tablets of favipiravir using superdisintegrants: preparation, optimization and in vitro evaluation. JPRI 2021;33:28-39. doi: 10.9734/jpri/ 2021/v33i631187.

Sharma D, Maheshwari D, Philip G, Rana R, Bhatia S, Singh M. Formulation and optimization of polymeric nanoparticles for intranasal delivery of lorazepam using box-behnken design: in vitro and in vivo evaluation. BioMed Res Int. 2014;2014:156010. doi: 10.1155/2014/156010. PMID 25126544.

Imtiaz N, Majee SB, Biswas GR. Development and characterization of oral swellable rapid-release film with superdisintegrant-surfactant. Int J Curr Pharm Sci. 2021;13(1):75-80. doi: 10.22159/ijcpr.2021v13i1.40821.

Zhou YZ, Alany RG, Chuang V, Wen J. Optimization of PLGA nanoparticles formulation containing L-dopa by applying the central composite design. Drug Dev Ind Pharm. 2013;39(2):321-30. doi: 10.3109/03639045.2012.681054, PMID 22607101.

Wan Maznah Wan Ishak, Mohd Hanif Zulfakar. Optimization, development, and safety evaluation of olive oil nanoemulsion for topical application: a response surface methodology. Asian J Pharm Clin. 2022;15(9):167-73. doi: 10.22159/ajpcr.2022.v15i9.45964.

Nandy BC, Mazumder B. Formulation and characterizations of delayed-release multi particulates system of indomethacin: optimization by response surface methodology. Curr Drug Deliv. 2014;11(1):72-86. doi: 10.2174/15672018113109990041, PMID 24783236.

Teja SPS, Damodharan N. 3Full factorial model for particle size optimisation of methotrexate loaded chitosan nanocarriers: A design of experiments (DOE) approach. BioMed Res Int. 2018;2018:7834159. doi: 10.1155/2018/7834159, PMID 30356374.

Abbas Z, Marihal S. Gellan gum-based mucoadhesive microspheres of almotriptan for nasal administration: formulation optimization using factorial design, characterization, and in vitro evaluation. J Pharm Bioallied Sci. 2014;6(4):267-77. doi: 10.4103/0975-7406.142959. PMID 25400410.

Sahin A, Esendagli G, Yerlikaya F, Caban Toktas S, Yoyen Ermis D, Horzum U. A small variation in average particle size of PLGA nanoparticles prepared by nanoprecipitation leads to considerable change in nanoparticles’ characteristics and efficacy of intracellular delivery. Artif Cells Nanomed Biotechnol. 2017;45(8):1657-64. doi: 10.1080/ 21691401.2016.1276924, PMID 28084837.

Mainardes RM, Evangelista RC. PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution. Int J Pharm. 2005;290(1-2):137-44. doi: 10.1016/j.ijpharm.2004.11.027. PMID 15664139.

Sharma N, Madan P, Lin S. Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: a co-surfactant study. Asian J Pharm Sci. 2016;11(3):404-16. doi: 10.1016/j.ajps.2015.09.004.

Kalidas S, Geetha P. Development and optimization of astragalin-loaded polymeric nanoparticles using central composite factorial design. Int J App Pharm. 2022;14(5):69-77. doi: 10.22159/ijap.2022v14i5.44315.

Rahbarian M, Mortazavian E, Dorkoosh FA, Rafiee Tehrani M. Preparation, evaluation and optimization of nanoparticles composed of thiolated triethyl chitosan: A potential approach for buccal delivery of insulin. J Drug Deliv Sci Technol. 2018;44:254-63. doi: 10.1016/j.jddst.2017.12.016.jddst.2017.12.016.

Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10(2):57. doi: 10.3390/pharmaceutics10020057, PMID 29783687.

Ekambaram P, Abdul HS A. Formulation and evaluation of solid lipid nanoparticles of ramipril. J Young Pharm. 2011;3(3):216-20. doi: 10.4103/0975-1483.83765, PMID 21897661.

Pandey P, Chellappan DK, Tambuwala MM, Bakshi HA, Dua K, Dureja H. Central composite designed formulation, characterization and in vitro cytotoxic effect of erlotinib loaded chitosan nanoparticulate system. Int J Biol Macromol. 2019;141:596-610. doi: 10.1016/j.ijbiomac.2019.09.023. PMID 31494160.

Devi KV, Bhosale UV. Formulation and optimization of polymeric nano drug delivery system of acyclovir using 3² full factorial design. Int J PharmTech Res. 2009;1(3):644-53.

Doniparthi J, B JJ. Novel tamarind seed gum-alginate-based multi-particulates for sustained release of dalfampridine using response surface methodology. Int J Biol Macromol. 2020;144:725-41. doi: 10.1016/j.ijbiomac.2019.11.203. PMID 31843610.

Padmasri B, Nagaraju R. Formulation and evaluation of novel insitu gel system in the management of rheumatoid arthritis. Int J App Pharm. 2022;14(5):62-8. doi: 10.22159/ ijap.2022v14i5.43792.

Salmanpour Mohsen, Saeed Vaghefi M, Abolmaali SS, Tamaddon AM. Sterically stabilized polyionic complex nanogels of chitosan lysate and PEG-b-Polyglutamic acid copolymer for the delivery of active irinotecan metabolite (SN-38). Curr Drug Deliv. 2021;18(6):741-52. doi: 10.2174/1567201817999201103195846, PMID 33155910.

Niharika Girish M, KK. Solid lipid nanoparticles of rebamipide: formulation, characterization and in vivo pharmacokinetic evaluation. Int J App Pharm. 2022;14(2):143-50. doi: 10.22159/ijap.2022v14i2.42945.

##submissions.published##

07-01-2023

##issue.issue##

##section.section##

Original Article(s)