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

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

DOI:

https://doi.org/10.22159/ijap.2023v15i1.46289

Keywords:

Favipiravir, PLGA, Central composite design

Abstract

Objective: The objective of this study is to fabricate favipiravir-loaded PLGA nanoparticulate systems that can increase the solubility along with 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 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 109.7nm and the percent cumulative drug release showed 86.46% drug release over 720 minutes. The drug release was found to follow first order release kinetics with an 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 minutes.

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References

Saiprasad Patil, Shashank Joshi, Jalil Parkar, Abdul Ansari, Agam Vora. Role of favipiravir in the treatment of Covid- 19. Int J Infect Dis. 2020; 102:501-8. doi: 10.1016/j.ijid.2020.10.069, PMID: 33130203.

Ran Chen, Tingting Wang, Jie Song, Daojun Pu, Dan He. Antiviral Drug Delivery system for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics. Int J Nanomed.2021; 16: 4959-84. doi: 10.2147/IJN.S315705, PMID: 34326637.

Ryta Lagocka, Violetta Dziedziejko, Patrycja Klos, Andrzej Pawlik. Favipiravir in therapy of viral infections. J Clin Med. 2021; 10: 273-89. doi: 10.3390/jcm10020273, PMID: 33451007.

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

Esfanjani AF, Seid Mahdi Jafari. Biopolymer nanoparticles and natural nanocarriers for nano-encapsulation of phenolic compounds. Colloids and 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; 1849:012001. doi: 10.1088/1742-6596/1849/1/012001.

Alaas S. Tulab, Wing Hin Lee. Physicochemical characteristics and In-vitro toxicity/anti-SARS-CoV-2 activity of favipiravir solid lipid nanoparticles. Pharmaceuticals. 2021; 14(10): 1059-72. doi: 10.3390/ph14101059, PMID: 34681283.

Chunchun Yao, Feng Xiang, Zhangyi Xu. 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: 64-8. doi: 10.1007/s00894-022-05054-6.

Naseeb Basha Shaik, Lakshmi PK, Basava Rao VV. Formulation and evaluation of favipiravir proliposomal powder for pulmonary delivery by nebulization. Int J Pharm Res. 2022; 11(2): 36-44. doi: 10.51847/4McfhPccXs.

D. Avinash, Madhu Gudipati, M. V. Ramana, Pallavi Vadlamudi. Mouth dissolving tablets of favipiravir using Superdisintegrant: Preparation, optimisation and in-vitro evaluation. J Pharm Res. 2021; 33(6): 28-39. doi: 10.9734/JPRI/2021/v33i631187.

F. Danhier, E. Ansorena, J.M. Silva, R. Coco, A. le Breton. 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.

D. Nagasamy Venkatesh, Mahendran Baskaran, Veera Venkata Satyanarayana Reddy Karri, Kollipara Radhakrishna, Sandip Goti. Fabrication and in vivo evaluation of Nelfinavir loaded PLGA nanoparticles for enhancing oral bioavailability and therapeutic effect. Saudi Pharm J. 2015; 23(6): 101-8. doi: 10.1016/j.jsps.2015.02.021, PMID: 26702262.

Khushwant S. Yadav, Krutika K. Sawant. Modified Nanoprecipitation method for Preparation of Cytarabine- Loaded PLGA Nanoparticles. AAPS Pharm SciTech. 2010; 11(3): 1456-65. doi:10.1208/s12249-010-9519-4, PMID: 20842542.

Biagio Todaro, Aldo Moscardini, Stefano Luin. Pioglitazone loaded PLGA Nanoparticles: Towards the most reliable synthesis method. Int J Mol Sci. 2022; 23(5): 2522-26. doi: 10.3390/ijms23052522, PMID: 35269665.

Grace Sebastian, Sneha Priya, Jainey P. James, Abhilash M. M, Sannidhi, Vinay kiran prabhu. Computational tools assisted formulation optimization of nebivolol Hydrochloride loaded PLGA nanoparticles by 32 factorial designs. Int J Appl Pharm. 2022; 14(4): 251-8. doi: 10.22159/ijap.2022v14i4.44865.

Ongun Mehmet Saka, Umut Can Oz, Berrin Kuçukturkmen, Burcu Devrim, Asuman Bozkır. Central composite design for optimization of zoledronic acid loaded PLGA nanoparticles. J Pharm Innov. 2018; 15:03-14. doi: 10.1007/s12247-018-9365-6.

Jaleh Varshosaz, Solmaz Ghaffari, Mohammad Reza Khoshayand, Fatemeh Atyabi, Shirzad Azarmi, Farzad Kobarfard. 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.

Bibhu Prasad Panda. Impact of Statistical Central composite Face centered Design Approach on method and process optimisation of Metformin Hydrochloride loaded PLGA Nanoformulations. Micro and Nanosystems. 2017; 9:55-71. doi: 10.2174/1876402909666170817113542.

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

Haniza Hassan, Siti Khadijah Adam, Ekram Alias, Meor Mohd Redzuan Meor Mohd Affandi, Ahmad Fuad Shamsuddin, Rusliza Basir. Central composite design for formulation and optimisation of solid lipid nanoparticles to enhance oral bioavailability of acyclovir. Molecules. 2021. 26(18): 5432. doi: 10.3390/molecules26185432, PMID: 34576904.

Mamat Yadav, Pankaj Aggarwal, Deepika Yadav, Anand Singh. Formulation and evaluation of clobetasol-17-propionate-loaded carboxymethyl chitosan nanoparticle. Asian J Pharm Clin. 2022; 15(9): 88-93. doi: 10.22159/ajpcr. 2022.v15i9.45743.

R. Seda Tigli, Gokce Kaynak Bayrak, Menemse Gumusdereligolu. Salinomycin encapsulated nanoparticles as a targeting vehicle for glioblastoma cells. J Bio Med Research. 2015; 104(2): 543-50. doi: 10.1002/jbm.a.35591, PMID: 26476239.

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

Mohsen Salmanpour, Mahvan Saeed, Vagheif, Samira Sadat Aboolmalai, Ali Mohamad Tamaddon. Sterically stabilised polyionic complex nanogels of chitosan lysate and PEG-b- polyglutamic acid copolymer for the delivery of irinotecan active metabolite (SN-38). Current Drug Delivery. 2021;18(6): 741-52. doi: 10.2174/156720187999201103195846.

Haitao Yang, Sravan Kumar Patel, Jing Li, Kenneth E. Palmer, Brid Devlin, Lisa C. Rohan. 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.

D. Avinash, Madhu Gudipati, M. V. Ramana, Pallavi Vadlamudi. Mouth dissolving tablets of favipiravir using Superdisintegrant: Preparation, optimisation and in-vitro evaluation. J Pharm Res. 2021; 33(6): 28-39. doi: 10.9734/jpri/2021/v33i631187.

Deepak Sharma, Dipika Maheshwari, Gilphy Philip, Ravish Rana, Shanu Bhatia, Manisha Singh, Reema Gabrani. 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; 20: 1-14. Doi: 10.1155/2014/156010, PMID: 25126544.

Neha Imitiaz, Supata Biswas Majee, Gopa Roy Biswas. Development and characterization of oral swellable rapid release film with superdisintegrant-surfactant. Int J Curr Pharm. 2021; 13(1): 75-80. doi: 10.22159/ijcpr.2021v13i1.40821.

Yong Zhi Zhou, Raid G. Alany, Victor Chuang, Jingyuan Wen. Optimization of PLGA nanoparticles formulation containing L-DOPA by applying the central composite design. Drug Development and Industrial Pharmacy. 2012; 39(2): 321-30. doi: 10.3109/03639045.2012.681054.

Wan maznah wan ishak1, 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.

Bankim Chandra Nandy, Bhaskar Mazumder. Formulation and Characterisation of delayed release multi-particulate system of indomethacin: Optimisation by response surface methodology. Curr Drug Deliv. 2014; 11(1): 72-86. doi: 10.2174/15672018113109990041.

S.P. Surya Teja, N.Damodharan. 23 Full factorial model for particle size optimisation of methotrexate loaded chitosan nanocarriers: A design of experiments (DOE) approach. Biomed Res Int. 2018; 11: 7834159. doi: 10.1155/2018/7834159, PMID: 30356374.

Zaheer Abbas, Sachin Marihal. Gellan gum based muchoadhesive microspheres of almotriptan for nasal administration: Formulation optimisation using factorial design, characterisation and invitro evaluation. J Pharm Bioall 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.

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

Navneet Sharma, Parshotam Madan, Senshang Lin. Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: A co-surfactant study. Asian J. Pharm Sci. 2015; 11: 404-16. doi: 10.1016/j.ajps.2015.09.004.

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

Marzieh Rahbarian, Elahe Mortazavian, Farid Abedin Dorkoosh, Morteza Rafiee-Tehrani. 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.

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.

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

Parijat Pandey, Dinesh Kumar Chellappan, Murtaza M. Tambuwala, Hamid A. Bakshi, Kamal Dua, Harish Dureja. 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 Kusum V, Bhosale U.V. 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.

Jyosna Doniparthi, B. Jeevana Jyothi. Novel tamarind seed gum-alginate based multi-particulates for sustained release of dalfampridine using response surface methodology. Int J Biol Macromol. 2019; 144: 725-41. doi: 10.1016/j.ijbiomac.2019.11.203, PMID: 31843610.

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

Mohsen Salmanpour , Mahvand Saeed-Vaghefi , Samira Sadat Abolmaali , Ali Mohamad Tamaddon. Sterically Stabilized Polyionic Complex Nanogels of Chitosan Lysate and PEG-b-Polyglutamic Acid Copolymer for the Delivery of Irinotecan Active Metabolite. Curr Drug Deliv. 2021; 18(6): 741-52. doi: 10.2174/1567201817999201103195846, PMID: 33155910.

Niharika girish mirmeera, Kannan k. Solid lipid nanoparticles of rebamipide: formulation, characterization and in vivopharmacokinetic evaluation. Int J Appl Pharm. 2022; 14(2): 143- 50. doi:10.22159/ijap.2022v14i2.42945.

Published

21-10-2022

How to Cite

R, V. K., & B., J. J. (2022). CENTRAL COMPOSITE FACE CENTERED DESIGN BASED OPTIMISATION, DEVELOPMENT AND CHARACTERISATION OF FAVIPIRAVIR LOADED PLGA NANOPARTICLES. International Journal of Applied Pharmaceutics, 15(1). https://doi.org/10.22159/ijap.2023v15i1.46289

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