RESPONSE SURFACE METHODOLOGY-AIDED DEVELOPMENT OF PIRFENIDONE-LOADED SOLID LIPID NANOPARTICLES FOR INTRAPULMONARY DRUG DELIVERY SYSTEM

Authors

  • KEVIN KWOK Laboratory of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Indonesia, Depok, West Java-16424, Indonesia https://orcid.org/0009-0003-6700-3724
  • GATOT SUHARIYONO Nuclear Metrology and Quality Safety Technology Research Center–Nuclear Power Research Organization, National Research and Innovation Agency, South Tangerang, Indonesia https://orcid.org/0000-0003-0274-2940
  • SILVIA SURINI Laboratory of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Indonesia, Depok, West Java-16424, Indonesia https://orcid.org/0000-0003-1211-9706

DOI:

https://doi.org/10.22159/ijap.2024v16i4.50231

Keywords:

Pirfenidone, Lipid nanoparticles, Formula optimization, Mass median aerodynamic diameter, Box-behnken design

Abstract

Objective: This study aims to determine the optimized Pirfenidone-loaded Solid Lipid Nanoparticles (P-SLN) formula for Intrapulmonary Drug Delivery System (IPDDS) using Response Surface Methodology (RSM).

Methods: Box-Behnken design was applied to create fifteen P-SLN formulas comprising three independent variables, namely lipid-to-drug ratio, polymer type, and polymer concentration, and three dependent variables, including particle size, Polydispersity Index (PDI), and entrapment efficiency. The P-SLNs were prepared by solvent injection followed by the ultrasonication method. Those formulas were optimized with the RSM approach using the Design Expert®. Then, the optimized P-SLN was further characterized for morphology, moisture content, aerodynamic performance, and dissolution profile.

Results: The optimization process, assisted by RSM, determined that the optimized P-SLN had a lipid-to-drug ratio of 6:1 and contained 0.5% Plasdone K-29/32. The resulting P-SLN had a spherical shape with a particle size of 212.7 nm, a PDI of 0.39, an entrapment efficiency of 95.02%, and a low moisture content of 1.59%. The optimized P-SLN also exhibited appropriate IPDDS required characteristics, including a Mass Median Aerodynamic Diameter (MMAD) ranging from 0.540–12.122 μm and a Respirable Fraction (RF) of 12.4%. Moreover, the release of pirfenidone from this optimized formula was 89.61% and 69.28% in pH 4.5 and 7.4 buffer media, respectively, in 45 min through a combination of diffusion and polymer swelling mechanisms.

Conclusion: The optimized P-SLN showed promising potential as an IPDDS for pirfenidone.

Downloads

Download data is not yet available.

References

Ruwanpura SM, Thomas BJ, Bardin PG. Pirfenidone: molecular mechanisms and potential clinical applications in lung disease. Am J Respir Cell Mol Biol. 2020;62(4):413-22. doi: 10.1165/rcmb.2019-0328TR, PMID 31967851.

Martinez FJ, Collard HR, Pardo A, Raghu G, Richeldi L, Selman M. Idiopathic pulmonary fibrosis. Nat Rev Dis Primers. 2017;3(17074):17074. doi: 10.1038/nrdp.2017.74, PMID 29052582.

Huang C, Huang L, Wang Y, Li X, Ren L, Gu X. 6 mo consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220-32. doi: 10.1016/S0140-6736(20)32656-8, PMID 33428867.

Zhou X, Yang D, Kong X, Wei C, LvQiu S, Wang L. Case report: pirfenidone in the treatment of post-COVID-19 pulmonary fibrosis. Front Med (Lausanne). 2022;9:(925703). doi: 10.3389/fmed.2022.925703, PMID 35733875.

Seto Y, Inoue R, Kato M, Yamada S, Onoue S. Photosafety assessments on pirfenidone: photochemical, photobiological, and pharmacokinetic characterization. J Photochem Photobiol B. 2013;120:44-51. doi: 10.1016/j.jphotobiol.2013.01.010, PMID 23419534.

Park JH, Jin HE, Kim DD, Chung SJ, Shim WS, Shim CK. Chitosan microspheres as an alveolar macrophage delivery system of ofloxacin via pulmonary inhalation. Int J Pharm. 2013;441(1-2):562-9. doi: 10.1016/j.ijpharm.2012.10.044, PMID 23142421.

Gulati N, Chellappan DK, MacLoughlin R, Dua K, Dureja H. Inhaled nano-based therapeutics for inflammatory lung diseases: recent advances and future prospects. Life Sci. 2021;285:(119969). doi: 10.1016/j.lfs.2021.119969, PMID 34547339.

Abdelaziz HM, Gaber M, Abd-Elwakil MM, Mabrouk MT, Elgohary MM, Kamel NM. Inhalable particulate drug delivery systems for lung cancer therapy: nanoparticles, microparticles, nanocomposites and nanoaggregates. J Control Release. 2018;269:374-92. doi: 10.1016/j.jconrel.2017.11.036, PMID 29180168.

Duan Y, Dhar A, Patel C, Khimani M, Neogi S, Sharma P. A brief review on solid lipid nanoparticles: part and parcel of contemporary drug delivery systems. RSC Adv. 2020;10(45):26777-91. doi: 10.1039/d0ra03491f, PMID 35515778.

Anggraini R, Surini S, Saputri FC. Formulation and characterization of bitter melon (Momordica charantia linn.) fruit fraction loaded solid lipid nanoparticles. Pharmacogn J. 2021;13(6):1347-54. doi: 10.5530/pj.2021.13.170.

Duong VA, Nguyen TT, Maeng HJ. Preparation of solid lipid nanoparticles and nanostructured lipid carriers for drug delivery and the effects of preparation parameters of solvent injection method. Molecules. 2020;25(20):1-36. doi: 10.3390/molecules25204781, PMID 33081021.

Zhao Y, Chang YX, Hu X, Liu CY, Quan LH, Liao YH. Solid lipid nanoparticles for sustained pulmonary delivery of Yuxingcao essential oil: preparation, characterization and in vivo evaluation. Int J Pharm. 2017;516(1-2):364-71. doi: 10.1016/j.ijpharm.2016.11.046, PMID 27884712.

Ebrahimi HA, Javadzadeh Y, Hamidi M, Jalali MB. Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles. Daru. 2015;23(1):46. doi: 10.1186/s40199-015-0128-3, PMID 26392174.

Lamidi S, Olaleye N, Bankole Y, Obalola A, Aribike E, Adigun I. Applications of response surface methodology (RSM) in product design, development and process optimization. In: Kayaroganam P, editor. Response surface methodology-research and applications. IntechOpen; 2023. doi: 10.5772/intechopen.106763.

Kumar R, Reji M. Response surface methodology (RSM): an overview to analyze multivariate data. Indian J Microbiol Res. 2023;9(4):241-8. doi: 10.18231/j.ijmr.2022.042.

Parmar VK, Desai SB, Vaja T. RP-HPLC and UV spectrophotometric methods for estimation of pirfenidone in pharmaceutical formulations. Indian J Pharm Sci. 2014;76(3):225-9. PMID 25035534.

Hasyyati US, Surini S, Suhariyono GS. Prospective pulmonary drug delivery system of pirfenidone microparticles for pulmonary fibrosis. J Appl Pharm Sci. 2023;09:95-105. doi: 10.7324/JAPS.2023.125985.

Surini S, Providya R, Putri KS. Formula optimization of rifampicin dry powder inhalation with chitosan-xanthan carrier using response surface methodology. J Appl Pharm Sci. 2019;9(1):33-41. doi: 10.7324/JAPS.2019.90106.

Abdo RW, Saadi N, Hijazi NI, Suleiman YA. Quality control and testing evaluation of pharmaceutical aerosols. In: Drug delivery systems. Netherland. Elsevier; 2019. p. 579-614.

Maboos M, Yousuf RI, Shoaib MH, Nasiri I, Hussain T, Ahmed HF. Effect of lipid and cellulose based matrix former on the release of highly soluble drug from extruded/spheronized, sintered and compacted pellets. Lipids Health Dis. 2018;17(1):136. doi: 10.1186/s12944-018-0783-8, PMID 29885655.

Kumar JA, Bhikshapathi DV. Development of nilotinib loaded solid lipid nanoparticles and optimization by central composite design approach. Int J App Pharm. 2022;14(2):172-80. doi: 10.22159/ijap.2022v14i2.43943.

Farsani PA, Mahjub R, Mohammadi M, Oliaei SS, Mahboobian MM. Development of perphenazine-loaded solid lipid nanoparticles: statistical optimization and cytotoxicity studies. BioMed Res Int. 2021;2021:(6619195). doi: 10.1155/2021/6619195, PMID 33997026.

He Y, Guo F. Micromechanical analysis on the compaction of tetrahedral particles. Chem Eng Res Des. 2018;136:610-9. doi: 10.1016/j.cherd.2018.06.019.

Putri KS, Ramadhani LS, Rachel T, Suhariyono G, Surini S. Promising chitosan-alginate combination for rifampicin dry powder inhaler to target active and latent tuberculosis. J Appl Pharm Sci. 2022;12(5):98-103.

Chaurasiya B, Zhao YY. Dry powder for pulmonary delivery: a comprehensive review. Pharmaceutics. 2020;13(1):1-28. doi: 10.3390/pharmaceutics13010031, PMID 33379136.

Hirota K, Hasegawa T, Nakajima T, Inagawa H, Kohchi C, Soma GI. Delivery of rifampicin-PLGA microspheres into alveolar macrophages is promising for treatment of tuberculosis. J Control Release. 2010;142(3):339-46. doi: 10.1016/j.jconrel.2009.11.020, PMID 19951729.

Labiris NR, Dolovich MB. Pulmonary drug delivery. Part II: the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol. 2003;56(6):600-12. doi: 10.1046/j.1365-2125.2003.01893.x, PMID 14616419.

Dudhat K, Patel H. Preparation and evaluation of pirfenidone loaded chitosan nanoparticles pulmonary delivery for idiopathic pulmonary fibrosis. Futur J PharmSci. 2022;8(1):1-14.

Ahmad I, Pandit J, Sultana Y, Mishra AK, Hazari PP, Aqil M. Optimization by design of etoposide loaded solid lipid nanoparticles for ocular delivery: characterization, pharmacokinetic and deposition study. Mater Sci Eng C Mater Biol Appl. 2019;100:959-70. doi: 10.1016/j.msec.2019.03.060, PMID 30948132.

Parvathaneni V, Kulkarni NS, Shukla SK, Farrales PT, Kunda NK, Muth A. Systematic development and optimization of inhalable pirfenidone liposomes for non-small cell lung cancer treatment. Pharmaceutics. 2020;12(3). doi: 10.3390/pharmaceutics12030206, PMID 32121070.

Rastogi V, Yadav P, Husain A, Verma A. Effect of hydrophilic and hydrophobic polymers on permeation of S-amlodipine besylate through intercalated polymeric transdermal matrix: 3(2) designing, optimization and characterization. Drug Dev Ind Pharm. 2019;45(4):669-82. doi: 10.1080/03639045.2019.1569035, PMID 30633579.

Aulia S, Winarti L, Wicaksono Y. Meloxicam self-nanoemulsifying drug delivery system: formulation and release kinetics analysis. Int J App Pharm. 2021;13Special Issue 4:188-93. doi: 10.22159/ijap.2021.v13s4.43856.

Hu L, Kong D, Hu Q, Gao N, Pang S. Evaluation of high-performance curcumin nanocrystals for pulmonary drug delivery both in vitro and in vivo. Nanoscale Res Lett. 2015;10(1):381. doi: 10.1186/s11671-015-1085-y, PMID 26428016.

Published

07-07-2024

How to Cite

KWOK, K., SUHARIYONO, G., & SURINI, S. (2024). RESPONSE SURFACE METHODOLOGY-AIDED DEVELOPMENT OF PIRFENIDONE-LOADED SOLID LIPID NANOPARTICLES FOR INTRAPULMONARY DRUG DELIVERY SYSTEM. International Journal of Applied Pharmaceutics, 16(4), 283–290. https://doi.org/10.22159/ijap.2024v16i4.50231

Issue

Section

Original Article(s)

Most read articles by the same author(s)

1 2 3 > >>