Investigating the influence of formulation variables on the preparation of nimodipine - loaded polymeric nanoparticles

Year 2025, Volume: 29 Issue: 2, 764 - 775

Asmaa Mohammed Rashid Mowafaq Mohammed Ghareeb

https://doi.org/10.12991/jrespharm.1664920

Abstract

Nimodipine (NID), as a calcium channel blocker used for the treatment of cerebral vasospasm, is classified as class II with poor water solubility, increasing its rate of dissolution by reducing particle size will boost its bioavailability. Nimodipine was formulated as Nimodipine-loaded nanoparticles using a solvent-anitsolvent nanoprecipitation approach to speed up the dissolving process and bring the particle size down to the nanorange. The purpose of the study was to investigate the impact of several variables on particle size, polydispersibility index, entrapment efficiency (%EE), and in vitro release behavior, including the type and quantity of polymers and surfactant, stirring speed, and solvent type. It is well established that particle size, polydispersity index, and entrapment efficiency are not only significantly affected by the formulating variables but can also affect drug release. The selected F12 was designated with a (1:4) drug:polymer w/w ratio as well; the (1:9) solvent:anti-solvent ratio was the best ratio to produce particle size (81.86 nm), polydispersibility index (0.053), and 90% entrapment efficiency. A morphology and compatibility study was conducted for the characterization of selected nanoparticles. The in-vitro drug release experiments were conducted, which show a marked improvement in the release profile via solubility enhancement.

Keywords

Nanoparticles, Nimodipine, Soluplus, Solvent - antisolvent, Zetapotential

References

• [1] Asasutjarit R, Sorrachaitawatwong C, Tipchuwong N, Pouthai S. Effect of formulation compositions on particle size and zeta potential of diclofenac sodium-loaded chitosan nanoparticles. World Acad Sci Eng Technol. 2013;7(9):568-570.
• [2] Jabbarli R, Pierscianek D, Rölz R, Darkwah Oppong M, Kaier K, Shah M, Taschner C, Mönninghoff C, Urbach H, Beck J, Sure U, Forsting M. Endovascular treatment of cerebral vasospasm after subarachnoid hemorrhage: More is more. Neurology. 2019;93(5):e458-e466. https://doi.org/10.1212/wnl.0000000000007862
• [3] Teng Z, Yu M, Ding Y, Zhang H, Shen Y, Jiang M, Liu P, Opoku-Damoah Y, Webster TJ, Zhou J. Preparation and characterization of nimodipine-loaded nanostructured lipid systems for enhanced solubility and bioavailability. Int J Nanomedicine. 2018;14:119-133. https://doi.org/10.2147%2FIJN.S186899
• [4] Ahad A, Al-Jenoobi FI, Al-Mohizea AM, Aqil M, Kohli K. Transdermal delivery of calcium channel blockers for hypertension. Expert Opin Drug Deliv. 2013;10(8):1137-1153. https://doi.org/10.1517/17425247.2013.783562
• [5] 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):1-7. https://doi.org/10.1186/s40580-016-0061-2
• [6] Nugroho AK, Kusumorini N, Pramono S, Martien R. An update on Nanoparticle Formulation Design of Piperine to Improve its Oral bioavailability: A Review. Iraqi J Pharm Sci. 2023;32(1):14-30. https://doi.org/10.31351/vol32iss1pp14-30
• [7] Raval JP, Naik DR, Amin KA, Patel PS. Controlled-release and antibacterial studies of doxycycline-loaded poly (ε-caprolactone) microspheres. J Saudi Chem. Soc. 2014;18(5):566-573. http://dx.doi.org/10.1016/j.jscs.2011.11.004
• [8] Alzalzalee R, Kassab H. Factors affecting the preparation of Cilnidipine nanoparticles. Iraqi J Pharm Sci. 2023;32(Suppl.):235-243. https://doi.org/10.31351/vol32issSuppl.pp235-243
• [9] Hadžiabdić J, Brekalo S, Rahić O, Tucak A, Sirbubalo M, Vranić E. Importance of stabilizers of nanocrystals of poorly soluble drugs. Maced Pharm Bull. 2020;66(03):145-146. http://dx.doi.org/10.33320/maced.pharm.bull.2020.66.03.072
• [10] Hong C, Dang Y, Lin G, Yao Y, Li G, Ji G, Shen H, Xie Y. Effects of stabilizing agents on the development of myricetin nanosuspension and its characterization: an in vitro and in vivo evaluation. Int J Pharm. 2014;477(1-2):251-260.https://doi.org/10.1016/j.ijpharm.2014.10.044
• [11] Li J, Wang Z, Zhang H, Gao J, Zheng A. Progress in the development of stabilization strategies for nanocrystal preparations. Drug Deliv. 2021;28(1):19-36. https://doi.org/10.1080/10717544.2020.1856224
• [12] Demirkurt B, Akdogan Y. Development of an ionic liquid based method for the preparation of albumin nanoparticles. ChemistrySelect. 2018;3(34):9940-9945. http://dx.doi.org/10.1002/slct.201801648
• [13] Toma NM, Abdulrasool AA. Preparation and evaluation of microneedles-mediated transdermal delivery of montelukast sodium nanoparticles. Int J Drug Deliv Technol. 2021;11(3):1075-1082. http://doi.org/10.25258/ijddt.11.3.74
• [14] Rashid AM, Abd-Alhammid SN. Formulation and characterization of itraconazole as nanosuspension dosage form for enhancement of solubility. Iraqi J Pharm Sci. 2019;28(2):124-133. https://doi.org/10.31351/vol28iss2pp124-133
• [15] Hamed HE, Hussein AA. Preparation, in vitro and ex-vivo evaluation of mirtazapine nanosuspension and nanoparticles incorporated in orodispersible tablets. Iraqi J Pharm Sci. 2020;29(1):62-75. https://doi.org/10.31351/vol29iss1pp62-75
• [16] Salatin S, Barar J, Barzegar-Jalali M, Adibkia K, Kiafar F, Jelvehgari M. Development of a nanoprecipitation method for the entrapment of a very water soluble drug into Eudragit RL nanoparticles. Res Pharm Sci. 2017;12(1):1. https://doi.org/10.4103%2F1735-5362.199041 [17] Attia MS, Elshahat A, Hamdy A, Fathi AM, Emad-Eldin M, Ghazy F-ES, Chopra H, Ibrahim TM. Soluplus® as a solubilizing excipient for poorly water-soluble drugs: Recent advances in formulation strategies and pharmaceutical product features. J Drug Deliv Sci Technol. 2023:104519. http://dx.doi.org/10.1016/j.jddst.2023.104519
• [18] 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(1):012024. http://dx.doi.org/10.1088/1757-899X/311/1/012024
• [19] Attia Shafie MA, Mohammed Fayek H. Formulation and evaluation of betamethasone sodium phosphate loaded nanoparticles for ophthalmic delivery. J Clin Exp Ophthalmol. 2013;4(273):2. http://dx.doi.org/10.4172/2155-9570.1000273
• [20] Ullah F, Iqbal Z, Khan A, Khan SA, Ahmad L, Alotaibi A, Ullah R, Shafique M. Formulation Development and Characterization of pH responsive polymeric nano-pharmaceuticals for targeted delivery of anti-cancer drug (Methotrexate). Front Pharmacol. 2022;13:911771. https://doi.org/10.3389/fphar.2022.911771
• [21] Jassem N, Rajab N. Formulation and in vitro evaluation of azilsartan medoxomil nanosuspension. Int J Pharm Pharm Sci. 2017;9(7):110. http://dx.doi.org/10.22159/ijpps.2017v9i7.18917
• [22] 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):102574-102592. https://doi.org/10.1039/C5RA15859A
• [23] Mohammad-Beigi H, Shojaosadati SA, Morshedi D, Mirzazadeh N, Arpanaei A. The effects of organic solvents on the physicochemical properties of human serum albumin nanoparticles. Iran J Biotechnol. 2016;14(1):45. https://doi.org/10.15171%2Fijb.1168
• [24] Rao JP, Geckeler KE. Polymer nanoparticles: Preparation techniques and size-control parameters. Prog Polym Sci. 2011;36(7):887-913. http://dx.doi.org/10.1016%2Fj.progpolymsci.2011.01.001
• [25] Tan H, Diddens C, Mohammed AA, Li J, Versluis M, Zhang X, Lohse D. Microdroplet nucleation by dissolution of a multicomponent drop in a host liquid. J Fluid Mech. 2019;870:217-246. https://doi.org/10.48550/arXiv.1811.03517
• [26] Beck-Broichsitter M. Solvent impact on polymer nanoparticles prepared nanoprecipitation. Colloids Surf. A Physicochem Eng Asp. 2021;625:126928. https://doi.org/10.1016/j.colsurfa.2021.126928
• [27] Bovone G, Cousin L, Steiner F, Tibbitt MW. Solvent controls nanoparticle size during nanoprecipitation by limiting block copolymer assembly. Macromolecules. 2022;55(18):8040-8048. https://doi.org/10.1021/acs.macromol.2c00907
• [28] Kim M-S, Song H-S, Park HJ, Hwang S-J. Effect of solvent type on the nanoparticle formation of atorvastatin calcium by the supercritical antisolvent process. Chem Pharm Bull. 2012;60(4):543-547. https://doi.org/10.1248/cpb.60.543
• [29] Hernández-Giottonini KY, Rodríguez-Córdova RJ, Gutiérrez-Valenzuela CA, Peñuñuri-Miranda O, Zavala-Rivera P, Guerrero-Germán P, Lucero-Acuña A. PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: Effects of formulation parameters. Rsc Advances. 2020;10(8):4218-4231. https://doi.org/10.1039/C9RA10857B
• [30] Alexander K, Thomas EMl. Concepts for the Stabilization of Metal Nanoparticles in Ionic Liquids. In: Scott H. (Eds). Applications of Ionic Liquids in Science and Technology. Rijeka: IntechOpen; 2011. p. Ch. 12. http://dx.doi.org/10.5772/22111
• [31] Ünal H, Öztürk N, Bilensoy E. Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin. Beilstein J Org Chem. 2015;11(1):204-212. https://doi.org/10.3762/bjoc.11.22
• [32] Fayyad MS, Ghareeb MM, Kassab HJ. Study of some variables affecting product properties of felodipine nano precipitation. Int J Pharm Sci Rev Res. 2017;42:265-268.
• [33] Dagtepe P, Chikan V. Quantized Ostwald ripening of colloidal nanoparticles. J Phys Chem. C 2010;114(39):16263-16269. http://dx.doi.org/10.1021/jp105071a
• [34] Li J, Fu Q, Liu X, Li M, Wang Y. Formulation of nimodipine nanocrystals for oral administration. Arch Pharm Res. 2016 Feb;39(2):202-212. https://doi.org/10.1007/s12272-015-0685-5
• [35] Alhagiesa AW, Ghareeb MM. The Formulation and characterization of nimodipine nanoparticles for the enhancement of solubility and dissolution rate. Iraqi J Pharm Sci. 2021;30(2):143-152. https://doi.org/10.31351/vol30iss2pp143-152
• [36] Jassim ZE, Hussein AA. Formulation and evaluation of clopidogrel tablet incorporating drug nanoparticles. Int J Pharm Pharm Sci. 2014;6(1):838-851.
• [37] Rajab NA, Jassem NA. A Design and in vitro evaluation of azilsartan medoxomil as a self-dispersible dry nanosuspension. Der Pharm Sin. 2018;9(1):12-32. http://dx.doi.org/10.13140/RG.2.2.22215.93606
• [38] Zu Y, Li N, Zhao X, Li Y, Ge Y, Wang W, Wang K, Liu Y. In vitro dissolution enhancement of micronized l-nimodipine by antisolvent re-crystallization from its crystal form H. Int J Pharm. 2014;464(1-2):1-9. https://doi.org/10.1016/j.ijpharm.2014.01.020
• [39] Alhagiesa AW, Ghareeb MM. Formulation and evaluation of nimodipine nanoparticles incorporated within orodispersible tablets. Int J Drug Deliv Technol. 2020;10(4):547-552. http://doi.org/2010.25258/ijddt.10.4.7
• [40] Zeeshan F, Lin PY, Sheshala R. Application of similarity factor (f 2) and time required to drug release (t%) indicators for dissolution profiles comparison of paracetamol tablets. Indian J Pharm Educ Res. 2020;54(3). http://dx.doi.org/10.5530/ijper.54.3.114
• [41] Habbal H, Karabet F. Chitosan-(Prunus avium) gum nanocapsules loaded with orange peel extract: Nanocapsules loaded with orange peel extract. Iraqi J Pharm Sci. 2023;32(1):194-201. https://doi.org/10.31351/vol32iss1pp194-201.