DESIGN AND DEVELOPMENT OF SOLID LIPID NANOPARTICLES CONTAINING ROSUVASTATIN USING CENTRAL COMPOSITE DESIGN
DOI:
https://doi.org/10.22159/ijap.2025v17i1.52360Keywords:
Rosuvastatin calcium, Central composite design, and solid lipid nanoparticles, emulsifier, LipidAbstract
Objective: Rosuvastatin calcium, a BCS class II drug with low solubility, was optimized using a central composite design to improve its bioavailability.
Methods: The study utilized Kolliphor RH 40 as an emulsifier and glyceryl monostearate as a solid lipid in preparing solid lipid nanoparticle dispersion, optimizing formulations based on mean dissolution time and entrapment efficiency.
Results: The study analyzed the entrapment efficiency and mean dissolution time of the prepared solid lipid nanoparticles. The range of mean dissolution time was found 7.1+0.5 to 8.9+0.6 hours. The highest entrapment efficiency was found to be 90.28%, with a standard deviation of 0.2. The linear model was chosen based on data precision and trend, while the quadratic model was selected for mean dissolution time. The 3D view graph indicated the model/equation followed by the formulations. The optimized formulation had a particle size of 16.16+10 nm and particle size distribution index to 0.729+002, indicating high homogeneity. Transmission electron microscopy images and dynamic light scattering data were in correlation. XRD, DSC used to analyze the drug's transformation into amorphous form. The dissolution profile of different formulations was plotted, and the optimized formulation followed the Korsmeyer-Peppas model. FTIR showed drug peaks, indicating no interaction.
Conclusion: The study suggested that the bioavailability of rosuvastatin calcium can be enhanced through the preparation of solid lipid nanoparticles of smaller size and sustained release of rosuvastatin.
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De Jong WH, Borm PJ. Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine. 2008;3(2):133-49. doi: 10.2147/ijn.s596. PMID: 18686775; PMCID: PMC2527668.
Ghasemiyeh P, Mohammadi-Samani S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Res Pharm Sci. 2018 Aug;13(4):288-303. doi: 10.4103/1735-5362.235156.
Elmowafy M, Al-Sanea MM. Nanostructured lipid carriers (NLCs) as drug delivery platform: Advances in formulation and delivery strategies. Saudi Pharm J. 2021 Sep;29(9):999-1012. doi: 10.1016/j.jsps.2021.07.015.
Mukherjee S, Ray S, Thakur RS. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci. 2009 Jul;71(4):349-58
Naseri N, Valizadeh H, Zakeri-Milani P. Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Structure, Preparation and Application. Adv Pharm Bull. 2015 Sep;5(3):305-13. doi: 10.15171/apb.2015.043
Dawoud MHSHS, Fayez AMM, Mohamed RAA, Sweed NMM. Enhancement of the Solubility of Rosuvastatin Calcium by Nanovesicular Formulation: A Systematic Study Based on a Quality by Design Approach. Proceedings.2021;78(1):34. https://doi.org/10.3390/IECP2020-08698
Ma P, Dong X, Swadley CL, Gupte A, Leggas M, Ledebur HC, Mumper RJ. Development of idarubicin and doxorubicin solid lipid nanoparticles to overcome Pgp-mediated multiple drug resistance in leukemia. J Biomed Nanotechnol. 2009 Apr;5(2):151-61.
El-Telbany DFA, El-Telbany RFA, Zakaria S, Ahmed KA, El-Feky YA. Formulation and assessment of hydroxyzine HCL solid lipid nanoparticles by dual emulsification technique for transdermal delivery. Biomed Pharmacother. 2021 Nov;143:112130. doi: 10.1016/j.biopha.2021.112130.
Rai N, Madni A, Faisal A, Jamshaid T, Khan MI, Khan MM, Parveen F. Glyceryl Monostearate based Solid Lipid Nanoparticles for Controlled Delivery of Docetaxel. Curr Drug Deliv. 2021;18(9):1368-1376. doi: 10.2174/1567201818666210203180153.
Talele P, Sahu S, Mishra AK. Physicochemical characterization of solid lipid nanoparticles comprised of glycerol monostearate and bile salts. Colloids Surf B Biointerfaces. 2018 ; 1;172:517-525. doi: 10.1016/j.colsurfb.2018.08.067.
He J, Huang S, Sun X, Han L, Chang C, Zhang W, Zhong Q. Carvacrol Loaded Solid Lipid Nanoparticles of Propylene Glycol Monopalmitate and Glyceryl Monostearate: Preparation, Characterization, and Synergistic Antimicrobial Activity. Nanomaterials (Basel). 2019;14;9(8):1162. doi: 10.3390/nano9081162.
Torrado-Salmerón C, Guarnizo-Herrero V, Torrado G, Peña MÁ, Torrado-Santiago S, de la Torre-Iglesias PM. Solid dispersions of atorvastatin with Kolliphor RH40: Enhanced supersaturation and improvement in a hyperlipidemic rat model. Int J Pharm. 2023; 25;631:122520. doi: 10.1016/j.ijpharm.2022.122520.
Yasir M, Chauhan I, Ameeduzzafar Z, Verma M, Noorulla K M, AbdurazakT,Nabil A, Misbahu H, Dinesh P, Gurmesa G, Debesa D, Sara U.V.S. KumarN.Buspirone loaded solid lipid nanoparticles for amplification of nose to brain efficacy: formulation development, optimization by Box-Behnken design, in-vitro characterization and in-vivo biological evaluation.J.DrugDeliv.Sci.Technol.2021;61:112130. DOI: 10.3109/08982100903443065.
Sohail S, Shah FA, Zaman SU, Almari AH, Malik I, Khan SA, Alamro AA, Zeb A, Din FU. Melatonin delivered in solid lipid nanoparticles ameliorated its neuroprotective effects in cerebral ischemia. Heliyon. 2023; 3;9(9):e19779. doi: 10.1016/j.heliyon.2023.e19779.
Emami J, Mohiti H, Hamishehkar H, Varshosaz J. Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design. Res Pharm Sci. 2015;10(1):17-33. PMID: 26430454; PMCID: PMC4578209.
Dhiman N,Awasthi R, Sharma B, Kharkwal H, Kulkarni GT. Lipid Nanoparticles as carrier for Bioactive Delivery. Front Chem. 2021;9:580118.https://doi.org/10.3389/fchem.2021.580118.
Bhupinder K, NewtonM. J. Acyclovir Solid Lipid Nanoparticles for Skin Drug Delivery: Fabrication, Characterization and In vitro Study. Recent Pat. Drug Deliv. Formul.2017;11(2),132–146.https://doi.org/10.2174/1872211311666170117123403.
Stefanov SR, Andonova VY. Lipid Nanoparticulate Drug Delivery Systems: Recent Advances in the Treatment of Skin Disorders. Pharmaceuticals (Basel). 2021;26;14(11):1083. doi: 10.3390/ph14111083. PMID: 34832865; PMCID: PMC8619682.
Garg A, Sharma GS, Goyal AK, Ghosh G, Si SC, Rath G. Recent advances in topical carriers of anti-fungal agents.Heliyon.2020;19;6(8):e04663. doi: 10.1016/j.heliyon.2020.e04663.
Chen HH, Huang WC, Chiang WH, Liu TI, Shen MY, Hsu YH, Lin SC, Chiu HC. pH-Responsive therapeutic solid lipid nanoparticles for reducing P-glycoprotein-mediated drug efflux of multidrug resistant cancer cells. Int J Nanomedicine. 2015 ; 5;10:5035-48. doi: 10.2147/IJN.S86053. PMID: 26346762; PMCID: PMC4531030.
Kumar M, Bishnoi RS, Shukla AK, Jain CP. Techniques for Formulation of Nanoemulsion Drug Delivery System: A Review. PrevNutr Food Sci. 2019;24(3):225-234. doi: 10.3746/pnf.2019.24.3.225. Epub 2019 Sep 30. PMID: 31608247; PMCID: PMC6779084.
KC Song, HSLee, IY Choung, K I Cho, Y Ahn, E J Choi.The effect of type of organic phase solvents on the particle size of poly(d,l-lactide-co-glycolide) nanoparticles, Colloids Surf. A: Physicochem. Eng. Asp .2006; 276: 162–167. https://doi.org/10.1016/j.colsurfa.2005.10.064
Weerapol Y, Manmuan S, Chaothanaphat N, Limmatvapirat S, Sirirak J, Tamdee P, Tubtimsri S. New Approach for Preparing Solid Lipid Nanoparticles with Volatile Oil-Loaded Quercetin Using the Phase-Inversion Temperature Method. Pharmaceutics. 2022;20;14(10):1984. doi: 10.3390/pharmaceutics14101984. PMID: 36297420; PMCID: PMC9607647.
Dara T, Vatanara A, Nabi Meybodi M, Vakilinezhad MA, Malvajerd SS, Vakhshiteh F, Shamsian A, Sharifzadeh M, Kaghazian H, Mosaddegh MH. Erythropoietin-loaded solid lipid nanoparticles: Preparation, optimization, and in vivo evaluation. Colloids Surf B Biointerfaces. 2019; 1;178:307-316. doi: 10.1016/j.colsurfb.2019.01.027. Epub 2019 Mar 1. PMID: 30878805.
Nandini PT, Doijad RC, Shivakumar HN, Dandagi PM. Formulation and evaluation of gemcitabine-loaded solid lipid nanoparticles. Drug Deliv. 2015;22(5):647-51. doi: 10.3109/10717544.2013.860502. Epub 2013 Nov 27. PMID: 24283392.
Kommavarapu P, Maruthapillai A. PalanisamyK. Preparation, Characterization and Evaluation of Elvitegravir-Loaded Solid Lipid Nanoparticles for Enhanced Solubility and Dissolution Rate.Tropical Journal of Pharmaceutical Research.2015; 14 (9): 1549-1556.DOI:10.4314/tjpr.v14i9.2.
Vemuri VD, Lankalapalli S. Cocrystal Construction Between Rosuvastatin Calcium and L-asparagine with Enhanced Solubility and Dissolution Rate. Turk J Pharm Sci. 2021; 31;18(6):790-798. doi: 10.4274/tjps.galenos.2021.62333.
Fatehi Hassanabad A. Current perspectives on statins as potential anti-cancer therapeutics: clinical outcomes and underlying molecular mechanisms. Transl Lung Cancer Res. 2019;8(5):692-699. doi: 10.21037/tlcr.2019.09.08.
Ahmed TA, Elimam H, Alrifai AO, Nadhrah HM, Masoudi LY, Sairafi WO, M El-Say K. Rosuvastatin lyophilized tablets loaded with flexible chitosomes for improved drug bioavailability, anti-hyperlipidemic and anti-oxidant activity. Int. J. Pharm. 2020;558:119791. doi: 10.1016/j.ijpharm.2020.119791
Ahmed TA. Development of rosuvastatin flexible lipid-based nanoparticles: promising nanocarriers for improving intestinal cells cytotoxicity. BMC PharmacolToxicol. 2020;21(1):14. doi: 10.1186/s40360-020-0393-8.
Yáñez JA, Wang SW, Knemeyer IW, Wirth MA, Alton KB. Intestinal lymphatic transport for drug delivery. Adv Drug Deliv Rev. 2011 ;63(10-11):923-42. doi: 10.1016/j.addr.2011.05.019.
Zhang Z, Lu Y, Qi J, Wu. An update on oral drug delivery via intestinal lymphatic transport. Acta Pharm Sin B.2021;11(8):2449-2468.DOI: 10.1016/j.apsb.2020.12.022.
Nguyen TTL, Duong, VA. Solid Lipid Nanoparticles. Encyclopedia2022;2, 952-973.https://doi.org/10.3390/encyclopedia2020063
Gulati, P, Dewangan H K. Aceclofenac Loaded Solid Lipid Nanoparticles: Optimization, In Vitro And Ex-Vivo Evaluation. Int. J. Appl. Pharm 2023; 15(4), 184–190.
Granato D, CaladoV.The use and importance of design of experiments (DOE) in process modeling in food science and technology.2014;1:1–18.DOI: 10.1002/9781118434635.ch1
Bevilacqua A, Corbo MR, Sinigaglia M. Design of experiments: a powerful tool in food microbiology;2010; 1419–1429.
Onugwu AL, Anthony A. Attama, Petra O. Nnamani, Sabastine O. Onugwu, Ebele B. Onuigbo, Vitaliy V. Khutoryanskiy. Development and optimization of solid lipid nanoparticles coated with chitosan and poly(2-ethyl-2-oxazoline) for ocular drug delivery ofciprofloxacin,J. DrugDeliv. Technol.2022;74:103527.https://doi.org/10.1016/j.jddst.2022.103527.
Ortiz AC, Yañez O, Salas-Huenuleo E, Morales JO. Development of a Nanostructured Lipid Carrier (NLC) by a Low-Energy Method, Comparison of Release Kinetics and Molecular Dynamics Simulation. Pharmaceutics. 2021;13(4):531.doi: 10.3390/pharmaceutics13040531.
Bhandari R, Kaur IP. A Method to Prepare Solid Lipid Nanoparticles with Improved Entrapment Efficiency of Hydrophilic Drugs. Current Nanoscience.2013;9:211-220.doi: 10.2174/1573413711309020008
Montenegro L, Sarpietro MG, Ottimo S, Puglisi G, Castelli F. Differential scanning calorimetry studies on sunscreen loaded solid lipid nanoparticles prepared by the phase inversion temperature method. Int J Pharm. 2011;415(1-2):301-6. doi: 10.1016/j.ijpharm.2011.05.076.
Shah M, Agrawal YK, Garala K, Ramkishan A. Solid lipid nanoparticles of a water soluble drug, ciprofloxacin hydrochloride. Indian J Pharm Sci. 2012 ;74(5):434-42. doi: 10.4103/0250-474X.108419.
Shen J, Burgess DJ. In Vitro Dissolution Testing Strategies for Nanoparticulate Drug Delivery Systems: Recent Developments and Challenges. Drug DelivTransl Res. 2013;3(5):409-415. doi: 10.1007/s13346-013-0129-z.
Üner M.Characterization and imaging of solid lipid nanoparticles and nanostructured lipid carriers. In: Aliofkhazraei M, editor. Handbook of Nanoparticles. Cham: Springer International Publishing.2016; 117-141.
Kumar S, Randhawa JK. Preparation and characterization of Paliperidone loaded solid lipid nanoparticles. Colloids Surf B Biointerfaces. 2013;102:562-8. doi: 10.1016/j.colsurfb.2012.08.052.
Madkhali OA. Perspectives and Prospective on Solid Lipid Nanoparticles as Drug Delivery Systems. Molecules. 2022 Feb ;27(5):1543. doi: 10.3390/molecules27051543.
Satapathy MK, Yen TL, Jan JS, Tang RD, Wang JY, Taliyan R, Yang CH. Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB. Pharmaceutics. 2021 ;13(8):1183. doi: 10.3390/pharmaceutics13081183.
Ekambaram P, Abdul HS. Formulation and evaluation of solid lipid nanoparticles of ramipril. J Young Pharm.2011; 3(3):216-220.doi: 10.4103/0975-1483.83765.
Ghadiri M, Fatemi S, Vatanara A, Doroud D, Najafabadi AR, Darabi M, Rahimi AA. Loading hydrophilic drug in solid lipid media as nanoparticles: statistical modeling of entrapment efficiency and particle size. Int J Pharm. 2012;424(1-2):128-37. doi: 10.1016/j.ijpharm.2011.12.037.
R. Awasthi, B. Bhushan, G. T. Kulkarni, in Targeting Chronic Inflammatory Lung Diseases Using Advanced Drug Delivery Systems, Amsterdam, Elsevier, 2020, pp. 171–209.
Shah M, Pathak K.Development and statistical optimization of solid lipid nanoparticles of simvastatin by using 2(3) full-factorial design. AAPS PharmSciTech.2010;11(2):489-496.doi: 10.1208/s12249-010-9414-z
Trotta M, Debernardi F, Caputo O. Preparation of solid lipid nanoparticles by a solvent emulsification-diffusion technique. Int J Pharm. 2003;257(1-2):153-60. doi: 10.1016/s0378-5173(03)00135-2.
Wang N, Hsu C, Zhu L, Tseng S, Hsu JP. Influence of metal oxide nanoparticles concentration on their zeta potential. J Colloid Interface Sci. 2013;407:22–8.
Akbari, B, Tavandashti, M P, Zandrahimi, M. Particle Size Characterization Of Nanoparticles–A Practical Approach. Iranian Journal Materials Science and Engineering, 2011;8(2), 48–56.
Apostolou M, Assi S, Fatokun AA, Khan I. The effects of solid and liquid lipids on the physicochemical properties of nanostructured lipid carriers. J. Pharm. Sci. 2021;110:2859–2872. doi: 10.1016/j.xphs.2021.04.012.
Dhoranwala KA, Shah P, Shah S.Formulation Optimization of Rosuvastatin Calcium-Loaded Solid Lipid Nanoparticles by 32 Full-Factorial Design. NanoWorld J .2015;1(4): 112-121.
Zambaux MF, Bonneaux F, Gref R, Maincent P, Dellacherie E, Alonso MJ, et al. Influence of experimental parameters on the characteristics of poly (lactic acid) nanoparticles prepared by a double emulsion method. J Control Release Elsevier. 1998;50: 31–40.
Reddy KR, Satyanarayana SV, Reddy VJ. Development And Evaluation Of Clobetasol–Loaded Solid Lipid Nanoparticles For Topical Treatment Of Psoriasis. International Journal of Applied Pharmaceutics, 2019;143–150. https://doi.org/10.22159/ijap.2019v11i5.33592.
Alshora DH, Ibrahim MA, Elzayat E, Almeanazel OT, Alanazi F. Rosuvastatin calcium nanoparticles: Improving bioavailability by formulation and stabilization codesign. PLoS One. Public Library of Science. 2018;13:e0200218.
Danaei M, Dehghankhold M, Ataei S, HasanzadehDavarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari MR. Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics. 2018;10(2):57. doi: 10.3390/pharmaceutics10020057.
Akanda M, Hossain S, Douroumis MD. Solid lipid nanoparticles: An effective lipid-based technology for cancer treatment.J. Drug Deliv. Technol.2023;86 : 104709.https://doi.org/10.1016/j.jddst.2023.104709
Schubert MA, Müller-Goymann CC. Solvent injection as a new approach for manufacturing lipid nanoparticles--evaluation of the method and process parameters. Eur J Pharm Biopharm. 2003;55(1):125-31. doi: 10.1016/s0939-6411(02)00130-3.
Kesharwani R, Sachan A, Singh S, Pate D. Formulation & Evaluation of Solid Lipid Nanoparticle (SLN) Based Topical Gel of Etoricoxib. J App Pharm Sci, 2016; 6 (10): 124-131.
QushawyM, Nasr A. Solid Lipid Nanoparticles (SLNs) As Nano Drug Delivery Carriers: Preparation, Characterization And Application. International Journal of Applied Pharmaceutics. 2019 ;1–9. https://doi.org/10.22159/ijap.2020v12i1.35312.
Dudhipala N, Veerabrahma K. Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: Pharmacokinetic and pharmacodynamic evaluation. Eur J Pharm Biopharm. 2017 Jan;110:47-57. doi: 10.1016/j.ejpb.2016.10.022.
Hunter RJ.Zeta Potential in Colloid Science: Principles and Applications Volume 2 of Colloid science, Colloid science.1981 A series of monographs volume 2 of Human Communication Research Series.:385.
Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015 Sep;33(9):941-51. doi: 10.1038/nbt.3330.
Dhoranwala KA, Shah P, Shah S. Formulation Optimization of Rosuvastatin Calcium-Loaded Solid Lipid Nanoparticles by 32 Full-Factorial Design. NanoWorld J.2015;1(4): 112-121.DOI: 10.17756/nwj.2015-015
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 Oct 18;25(20):4781. doi: 10.3390/molecules25204781.
Kishore CRP, Mohan GVK.Structural identification and estimation of Rosuvastatin calcium related impurities in Rosuvastatin calcium tablet dosage form. Analytical Chemistry Research .2016;12:17-27.DOI: 10.1016/j.ancr.2016.11.002.
Jores K, Mehnert W, Drechsler M, Bunjes H, Johann C, Mäder K. Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy. J Control Release. 2004; Mar 5;95(2):217-27. doi: 10.1016/j.jconrel.2003.11.012.
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