FORMULATION DEVELOPMENT AND EVALUATION OF PALIPERIDONE NANOSUSPENSION FOR SOLUBILITY ENHANCEMENT
DOI:
https://doi.org/10.22159/ijap.2024v16i4.51218Keywords:
Nanosuspension, Paliperidone, Schizophrenia, Solubility, BioavailabilityAbstract
Objective: The main objective of this work is to develop a nanosuspension formulation of paliperidone to overcome its low solubility and bioavailability issues. Stabiliser concentration (X1) and probe ultrasonication duration (X2) at three levels were tested for their effects on particle size (Y1) and saturation solubility (Y2) using a 32-factorial design.
Methods: The solvent-antisolvent method, followed by probe ultrasonication was used for the formulation of nanosuspension. The optimised nanosuspension was tested for particle size, saturation solubility, scanning electron microscopy, drug content, thermal analysis, zeta potential, Fourier transform infrared spectroscopy, in vitro dissolution, and in vivo study.
Results: The optimised formulation revealed a particle size of 293.4 ± 2.74 nm, saturation solubility of 173.61 ± 3.37 μg/ml, and zeta potential of-23.8 mV. Scanning electron microscope photographs indicated particle size less than 1 μm. Optimised nanosuspension showed 100% drug release within 30 minutes. Studies conducted in Wister rats have shown that the optimised nanosuspension demonstrated a 2.88 times higher maximum concentration and 2 times higher area under the curve. The stability studies demonstrated satisfactory stability over three months.
Conclusion: To summarise, this research showed the ability of nanosuspension to enhance the solubility and bioavailability of paliperidone.
Downloads
References
Munnangi SR, Youssef AA, Narala N, lakkala P, Narala S, Vemula SK. Drug complexes: a perspective from academic research and pharmaceutical market. Pharm Res. 2023 Jun;40(6):1519-40. doi: 10.1007/s11095-023-03517-w, PMID 37138135, PMCID PMC10156076.
Farghaly Aly U, Abou Taleb HA, Abdellatif AA, Sameh Tolba N. Formulation and evaluation of simvastatin polymeric nanoparticles loaded in hydrogel for optimum wound healing purpose. Drug Des Devel Ther. 2019;13:1567-80. doi: 10.2147/DDDT.S198413, PMID 31190737.
Patil AS, Hegde R, Gadad AP, Dandagi PM, Masareddy R, Bolmal U. Exploring the solvent-anti-solvent method of nanosuspension for enhanced oral bioavailability of lovastatin. Turk J Pharm Sci. 2021 Oct 28;18(5):541-9. doi: 10.4274/tjps.galenos.2020.65047, PMID 34708645, PMCID PMC8562113.
Taneja S, Shilpi S, Khatri K. Formulation and optimization of efavirenz nanosuspensions using the precipitation-ultrasonication technique for solubility enhancement. Artif Cells Nanomed Biotechnol. 2016 May;44(3):978-84. doi: 10.3109/21691401.2015.1008505, PMID 25724312.
Liu D, Xu H, Tian B, Yuan K, Pan H, Ma S. Fabrication of carvedilol nanosuspensions through the anti-solvent precipitation-ultrasonication method for the improvement of dissolution rate and oral bioavailability. AAPS PharmSciTech. 2012 Mar;13(1):295-304. doi: 10.1208/s12249-011-9750-7, PMID 22246736, PMCID PMC3299468.
Minwalla HD, Wrzesinski P, Desforges A, Caskey J, Wagner B, Ingraffia P. Paliperidone to treat psychotic disorders. Neurol Int. 2021 Jul 28;13(3):343-58. doi: 10.3390/neurolint13030035, PMID 34449689, PMCID PMC8396046.
Luvsannyam E, Jain MS, Pormento MK, Siddiqui H, Balagtas AR, Emuze BO. Neurobiology of schizophrenia: a comprehensive review. Cureus. 2022 Apr 8;14(4):e23959. doi: 10.7759/cureus.23959, PMID 35541299, PMCID PMC9080788.
Fadda HM, Chen X, Aburub A, Mishra D, Pinal R. A novel method for determining the solubility of small molecules in aqueous media and polymer solvent systems using solution calorimetry. Pharm Res. 2014 Jul;31(7):1735-43. doi: 10.1007/s11095-013-1278-y, PMID 24554115.
Wang Q, Jiao J, Cai Q, Wang Q, Zhou W. Design and evaluation of a zero-order controlled release system based on pre-hydrated constant release area prepared by compression coating technology. Pharm Dev Technol. 2021 Nov;26(10):1120-9. doi: 10.1080/10837450.2021.1998912, PMID 34698603.
Jain N, Verma A, Jain N. Preformulation studies of niosomal gel containing dipivefrin hydrochloride for antiglaucomatic activity. Int J Pharm Pharm Sci. 2024 Feb;16(2):17-23. doi: 10.22159/ijpps.2024v16i2.49174.
Purkayastha HD, Hossian SK. Nanosuspension: a modern technology used in drug delivery system. Int J Curr Pharm Sci. 2019 May;11(3):1-3. doi: 10.22159/ijcpr.2019v11i3.34098.
Elshafeey AH, El-Dahmy RM. Formulation and development of oral fast-dissolving films loaded with nanosuspension to augment paroxetine bioavailability: in vitro characterization, ex vivo permeation, and pharmacokinetic evaluation in healthy human volunteers. Pharmaceutics. 2021 Nov 5;13(11):1869. doi: 10.3390/pharmaceutics13111869, PMID 34834284, PMCID PMC8620498.
Alshweiat A, Katona G, Csoka I, Ambrus R. Design and characterization of loratadine nanosuspension prepared by ultrasonic-assisted precipitation. Eur J Pharm Sci. 2018 Sep 15;122:94-104. doi: 10.1016/j.ejps.2018.06.010, PMID 29908301.
Tibalinda P, Sempombe J, Shedafa R, Masota N, Pius D, Temu M. Formulation development and optimization of lamivudine 300 mg and tenofovir disoproxil fumarate (TDF) 300 mg FDC tablets by D-optimal mixture design. Heliyon. 2016 Dec 2;2(12):e00207. doi: 10.1016/j.heliyon.2016.e00207, PMID 27942608, PMCID PMC5137174.
Shah R, Soni T, Shah U, Suhagia BN, Patel MN, Patel T. Formulation development and characterization of lumefantrine nanosuspension for enhanced antimalarial activity. J Biomater Sci Polym Ed. 2021 May;32(7):833-57. doi: 10.1080/09205063.2020.1870378, PMID 33380264.
Ali HS, York P, Blagden N. Preparation of hydrocortisone nanosuspension through a bottom-up nanoprecipitation technique using microfluidic reactors. Int J Pharm. 2009 Jun 22;375(1-2):107-13. doi: 10.1016/j.ijpharm.2009.03.029, PMID 19481696.
Patil AS, Hegde R, Gadad AP, Dandagi PM, Masareddy R, Bolmal U. Exploring the solvent-anti-solvent method of nanosuspension for enhanced oral bioavailability of lovastatin. Turk J Pharm Sci. 2021 Oct 28;18(5):541-9. doi: 10.4274/tjps.galenos.2020.65047, PMID 34708645, PMCID PMC8562113.
Hao J, Gao Y, Zhao J, Zhang J, Li Q, Zhao Z. Preparation and optimization of resveratrol nanosuspensions by antisolvent precipitation using box-Behnken design. AAPS PharmSciTech. 2015 Feb;16(1):118-28. doi: 10.1208/s12249-014-0211-y, PMID 25209687, PMCID PMC4309822.
Raju A, Reddy AJ, Satheesh J, Jithan AV. Preparation and characterisation of nevirapine oral nanosuspensions. Indian J Pharm Sci. 2014 Jan;76(1):62-71. PMID 24799740, PMCID PMC4007257.
Thakkar HP, Patel BV, Thakkar SP. Development and characterization of nanosuspensions of olmesartan medoxomil for bioavailability enhancement. J Pharm Bioallied Sci. 2011 Jul;3(3):426-34. doi: 10.4103/0975-7406.84459, PMID 21966165, PMCID PMC3178951.
Umamaheswar K, Rambabu C. Spectrophotometric methods for the quantitative estimation of paliperidone in formulations. Chem Sci Trans. 2014 Jan;3(3):1156-62. doi: 10.7598/cst2014.771.
Jadhav K, Jadhav S, Sonawane D, Somvanshi D, Shah H, Patil P. Formulation and evaluation of miconazole nitrate loaded novel nanoparticle gel for topical delivery. J Pharm Res Int. 2021 Sep;33(44A):292-307. doi: 10.9734/jpri/2021/v33i44A32616.
Bhia M, Motallebi M, Abadi B, Zarepour A, Pereira Silva M, Saremnejad F. Naringenin nano-delivery systems and their therapeutic applications. Pharmaceutics. 2021 Feb 23;13(2):291. doi: 10.3390/pharmaceutics13020291, PMID 33672366, PMCID PMC7926828.
Detroja C, Chavhan S, Sawant K. Enhanced antihypertensive activity of candesartan cilexetil nanosuspension: formulation, characterization and pharmacodynamic study. Sci Pharm. 2011 Jul-Sep;79(3):635-51. doi: 10.3797/scipharm.1103-17, PMID 21886909, PMCID PMC3163369.
Li X, Yuan H, Zhang C, Chen W, Cheng W, Chen X. Preparation and in vitro/in vivo evaluation of curcumin nanosuspension with solubility enhancement. J Pharm Pharmacol. 2016 Aug;68(8):980-8. doi: 10.1111/jphp.12575, PMID 27283220.
Jahan N, Kousar F, Rahman KU, Touqeer SI, Abbas N. Development of nanosuspension of Artemisia absinthium extract as novel drug delivery system to enhance its bioavailability and hepatoprotective potential. J Funct Biomater. 2023 Aug 18;14(8):433. doi: 10.3390/jfb14080433, PMID 37623677, PMCID PMC10456093.
Dhapte V, Kadam V, Pokharkar V. Pyrimethamine nanosuspension with improved bioavailability: in vivo pharmacokinetic studies. Drug Deliv Transl Res. 2013 Oct;3(5):416-20. doi: 10.1007/s13346-012-0112-0, PMID 25788349.
Silki SVR, Sinha VR. Enhancement of in vivo efficacy and oral bioavailability of aripiprazole with solid lipid nanoparticles. AAPS PharmSciTech. 2018 Apr;19(3):1264-73. doi: 10.1208/s12249-017-0944-5, PMID 29313261.
Umamahesswar K, Ramu G, Rambabu C. A reverse phase HPLC method development and validation for the determination of paliperidone in pure and dosage forms. Chem Sci Trans. 2012 Jul;2(1):41-6. doi: 10.7598/cst2013.268.
Souto EB, Dias Ferreira J, lopez Machado A, Ettcheto M, Cano A, Camins Espuny A. Advanced formulation approaches for ocular drug delivery: state-of-the-art and recent patents. Pharmaceutics. 2019 Sep 6;11(9):460. doi: 10.3390/pharmaceutics11090460, PMID 31500106, PMCID PMC6781321.
Goel S, Sachdeva M, Agarwal V. Nanosuspension technology: recent patents on drug delivery and their characterizations. Recent Pat Drug Deliv Formul. 2019 Apr;13(2):91-104. doi: 10.2174/1872211313666190614151615, PMID 31203813, PMCID PMC6806604.
Jain N, Verma A, Jain N. Preformulation studies of niosomal gel containing dipivefrin hydrochloride for antiglaucomatic activity. Int J Pharm Pharm Sci. 2024 Jan;16(2):17-23. doi: 10.22159/ijpps.2024v16i2.49174.
Sumathi R, Tamizharasi S, Sivakumar T. Formulation and evaluation of polymeric nanosuspension of naringenin. Int J App Pharm. 2017 Oct;9(6):60-70. doi: 10.22159/ijap.2017v9i6.21674.
Kalvakuntla S, Deshpande M, Attari Z, Kunnatur BK. Preparation and characterization of nanosuspension of aprepitant by H96 process. Adv Pharm Bull. 2016 Mar;6(1):83-90. doi: 10.15171/apb.2016.013, PMID 27123422, PMCID PMC4845550.
Park K. Prevention of nanoparticle aggregation during freeze-drying. J Control Release. 2017 Feb 28;248:153. doi: 10.1016/j.jconrel.2017.01.038, PMID 28190423.
Gupta B, Sharma R. Formulation and in vitro characterization of the solid lipid nanoparticles of naftopidil for enhancing oral bioavailability. Asian J Pharm Clin Res. 2023 Jan;16(2):77-82. doi: 10.22159/ajpcr.2023.v16i2.46465.
Published
How to Cite
Issue
Section
Copyright (c) 2024 SHIVRAJ POPAT JADHAV, PRASHANT KUMAR DHAKAD, TAPASVI GUPTA, RITU GILHOTRA
This work is licensed under a Creative Commons Attribution 4.0 International License.
