A concise review on preparation methods used for the development of solid lipid nanoparticles
Solid lipid nanoparticles (SLNs) are in submicron size range nanoparticles and are made of biocompatible and biodegradable materials (mainly composed of lipids and surfactants) capable of incorporating both lipophilic and hydrophilic drugs. SLNs are also considered as substitute to other colloidal drug systems, also used as controlled systems and targeted delivery. SLNs can be considered as an alternative for oral drug delivery vehicle to improve the oral bioavailability of drugs, associated reduction of drug toxicity and stability of drug in both GIT and plasma. There are different techniques used for the preparation of SLNs. Generally, the preparation of SLNs and any other nanoparticle system necessitates a dispersed system as precursor; otherwise particles are produced through the use of a particular instrumentation. This review provides the summary on the techniques or methods used for the development of SLNs of poorly water soluble drugs for improved drug delivery.
Keywords: Solid lipid nanoparticles, controlled delivery, precursor, techniques.
2. Doodipala R. A review of novel formulation strategies to enhance oral delivery of zaleplon. J Bioequvi avail. 2016; 8(5): 211-213.
3. Rajitha R, Narendar D, Arjun N, Mahipal D and Nagaraj B. Colon delivery of naproxen: preparation, characterization and in vivo evaluation. IJPSN, 2016; 9(3), 1-10.
4. Plapied L, Duhem N, des Rieux A, Préat V. Fate of polymeric nanocarriers for oral drug delivery. Current opinion in colloid & interface science. 2011 Jun 1; 16(3):228-37.
5. Alekya T, Narendar D, Mahipal D, Arjun N, Nagaraj B. Design and evaluation of chronomodulated drug delivery of tramadol hydrochloride. Drug research. 2018 Mar; 68(03):174-80.
6. Thanki K, Gangwal RP, Sangamwar AT, Jain S. Oral delivery of anticancer drugs: challenges and opportunities. Journal of controlled release. 2013 Aug 28; 170(1):15-40.
7. Narendar D, Arjun N, Sunitha K, Harika K, Nagaraj B. Development of osmotically controlled oral drug delivery systems of tramadol hydrochloride: effect of formulation variables on in-vitro release kinetics. Asian J Pharm. 2016; 10(3): 1-10.
8. Arjun N, Narendar D, Sunitha K, Harika K, Madhusudan Rao Y and Nagaraj B. Development, evaluation and influence of formulation and process variables on in vitro performance of oral elementary osmotic device of atenolol. Int J Pharm Invest, 2016; 6(4):1-9.
9. Andrew J. Humberstone, William N. Charman. Lipid-based vehicles for the oral delivery of poorly water soluble drugs. Advanced Drug Delivery Reviews 1997; 25:103- 128.
10. Dudhipala N. Influence of Solid Lipid Nanoparticles on Pharmaco-dynamic Activity of Poorly Oral Bioavailable Drugs. International Journal of Pharmaceutical Sciences and Nanotechnology. 2020 Jul 11; 13(4):4979-83.
11. Damgé C., Michel C., Aprahamian M. Nanocapsules as carriers for oral peptide delivery. Journal of Controlled Release, 1990; 13:233–239.
12. Narendar D and Kishan V. Candesartan cilexetil nanoparticles for improved oral bioavailability. Ther deli, 2017; 8(2):79-88.
13. Florence AT. The oral absorption of micro-and nanoparticulates: neither exceptional nor unusual. Pharm Res 1997; 14:259-66.
14. Ettireddy S, Dudhipala N. Influence of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin on Enhancement of Solubility and Dissolution of Isradipine. Int J Pharma Sci and Nanotech. 2017; 10(3):3752-7.
15. Palem CR, Reddy ND, Satyanarayana G, Varsha BP. Development and optimization of Atorvastatin calcium-cyclodextrin inclusion complexed oral disintegrating tablets for enhancement of solubility, dissolution, pharmacokinetic and pharmacodynamic activity by central composite design. Int J Pharm Sci Nanotech 2016; 9(2): 1-11.
16. Butreddy A, Narendar D. Enhancement of solubility and dissolution rate of trandolapril sustained release matrix tablets by liquisolid compact approach. Asian J Pharm 2015; 9 (4): 290-297.
17. Chinna Reddy Palem, Ramesh Gannu, Narender D, Vamshi Vishnu Yamsani, and Madhusudan Rao Yamsani. Transmucosal Delivery of Domperidone from Bilayered Buccal Patches: In Vitro, Ex Vivo and In Vivo Characterization. Arch Pharm Res. 2011; 34(10):1701-1710.
18. Chinna Reddy Palem, Narendar D, Sunil Kumar Battu, Michael A. Repka and Madhusudan Rao Yamsani. Development, Optimization and in vivo Characterization of Domperidone Controlled Release Hot Melt Extruded Films for Buccal Delivery. Drug Dev Ind Pharm, 2016; 42(3):473-484.
19. Chinna Reddy Palem, Narendar D, Sunil Kumar Battu, Satyanarayana Goda, and Madhusudan Rao Yamsani. Combined dosage form of pioglitazone and felodipine as mucoadhesive pellets via hot melt extrusion for improved buccal delivery with application of quality by design approach. J Drug Del Sci Tech. 2015; 30:209-219.
20. Dudhipala N, Narala A, Bomma R. Recent Updates in the Formulation Strategies to Enhance the Bioavailability of Drugs Administered via Intranasal Route. J bioequ avail. 2016; 8(5):204-207.
21. Reddy, N.D., Chinna R. P., Sunil, R., & & Madhusudan, R. Y. Development of floating matrix tablets of Ofloxacin and Ornidazole in combined dosage form: in vitro and in vivo evaluation in healthy human volunteers. Int J Drug Deli, 2012; 4:462-469.
22. Reddy AB, Reddy ND. Development of multiple-unit floating drug delivery system of clarithromycin: formulation, in vitro dissolution by modified dissolution apparatus, in vivo radiographic studies in human volunteers. Drug research. 2017 Jul; 67(07):412-8.
23. Dudipala R, Palem, C.R., Reddy, S., & Rao, Y.M. Pharmaceutical development and clinical pharmacokinetic evaluation of gastroretentive floating matrix tablets of levofloxacin. Int J Pharma Sci and Nanotech, 2011; 4(3):1461-1467.
24. Narendar D, K. Someshwar, N. Arjun and Y. Madhusudan Rao. Quality by design approach for development and optimization of Quetiapine Fumarate effervescent floating matrix tablets for improved oral delivery. J Pharm Investigation., 2016; 46(3):253-263.
25. Donthi MR, Dudhipala NR, Komalla DR, Suram D, Banala N. Preparation and Evaluation of Fixed Combination of Ketoprofen Enteric Coated and Famotidine Floating Mini Tablets by Single Unit Encapsulation System. Journal of Bioequivalence & Bioavailability. 2015; 7(6):279.
26. Donthi MR, Dudipala N, Komalla DR, Suram D, Banala N. Design and Evaluation of Floating Multi Unit Mini Tablets (MUMTS) Muco Adhesive Drug Delivery System of Famotidine to Treat Upper Gastro Intestinal Ulcers. Journal of Pharmacovigilance. 2015 Oct 12.
27. Banala N, Peddapalli H, Dudhipala N, Chinnala KM. Transmucosal Delivery of Duloxetine Hydrochloride for Prolonged Release: Preparation, in vitro, ex vivo Characteri-zation and in vitro-ex vivo Correlation. International Journal of Pharmaceutical Sciences and Nanotechnology. 2018 Sep 30; 11(5):4249-58.
28. Narendar D, Arjun N, Karthik Yadav J and Ramesh Bomma. Amoxycillin Trihydrate Floating-Bioadhesive Drug Delivery System for Eradication of Helicobacter pylori: Preparation, In Vitro and Ex Vivo Evaluation. J bioequ avail. 2016; 8(3):118-124.
29. Nagaraj B, Anusha K, Narendar D, Sushma P. Formulation and evaluation of microemulsion-based transdermal delivery of duloxetine hydrochloride. International Journal of Pharmaceutical Sciences and Nanotechnology. 2020 Jan 31; 13(1):4773-82.
30. Shruthi K, Narendar D, Arjun N, Kishan V. Development and Antimicrobial Evaluation of Binary Ethosomal Topical Gel of Terbinafine Hydrochloride for the Treatment of Onychomycosis. Int. J. Pharm. Sci. Nanotechnol. 2018; 11:3998-4005.
31. Hu FQ, Jiang SP, Du YZ, et al. Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Coll Surf B: Biointerf, 2005; 45:167–73.
32. Vamshi Krishna M, Vijay Kumar B, Narendar Dudhipala. In-situ Intestinal Absorption and Pharmacokinetic Investigations of Carvedilol Loaded Supersaturated Self-Emulsifying Drug System. Pharm Nanotechnol. 2020 May 17. doi: 10.2174/2211738508666200517121637.
33. Pitta S, Dudhipala N, Narala A and Veerabrahma K. Development and evaluation of zolmitriptan transfersomes by Box-Behnken design for improved bioavailability by nasal delivery. Drug Dev Ind Pharm. 2018; 44(3):484-492.
34. Narendar D, Riyaz PMD, Ahmed AY, Nagaraj B. Effect of lipid and edge activator concentration on development of Aceclofenac loaded transfersomes gel for transdermal application: in vitro and ex vivo skin permeation. Dru Dev Ind Pharm. 2020; 46(8):1334-1344.
35. Tirumalesh C, Suram, D.; Dudhipala, N.; Banala, N. Enhanced pharmacokinetic activity of Zotepine via nanostructured lipid carrier system in Wistar rats for oral application. Pharm. Nanotechnol. 2020, 8(2):158-160.
36. Karri V, Butreddy A, Narender R. Fabrication of Efavirenz Freeze Dried Nanocrystals: Formulation, Physicochemical Characterization, In Vitro and Ex Vivo Evaluation. Advanced Science, Engineering and Medicine. 2015; 7(5): 385-392.
37. K. Nagaraj, D. Narendar and V. Kishan. Development of olmesartan medoxomil optimized nanosuspension using the Box–Behnken design to improve oral bioavailability. Drug Dev Ind Pharm, 2017; 43(7):1186-1196.
38. Butreddy A, Narala A, Dudhipala N. Formulation and characterization of Liquid Crystalline Hydrogel of Agomelatin: In vitro and Ex vivo evaluation. Journal of Applied Pharmaceutical Science. 2015 Sep; 5(09):110-4.
39. Müller RH. Colloidal carriers for controlled drug delivery and targeting: Modification, characterization and in vivo distribution. Taylor & Francis; 1991.
40. Bugnicourt L, Ladavière C. A close collaboration of chitosan with lipid colloidal carriers for drug delivery applications. Journal of Controlled Release. 2017 Jun 28; 256:121-40.
41. Barratt G. Colloidal drug carriers: achievements and perspectives. Cellular and Molecular Life Sciences CMLS. 2003 Jan 1; 60(1):21-37.
42. Müller R.H., Mehnert W., Lucks J.S., Schwarz .C, ZurMühlen A., Weyhers H., Freitas C., Ruhl D. Solid lipid nanoparticles (SLN)—An alternative colloidal carrier system for controlled drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, 1995; 41:62–69.
43. Mehnert, W., Mäder, K. (2001). Solid lipid nanoparticles production, characterization and applications. Adv Drug Deliv Rev. 47:165-196.
44. Dudhipala N. A Comprehensive Review on Solid Lipid Nanoparticles as Delivery Vehicle for Enhanced Pharmacokinetic and Pharmacodynamic Activity of Poorly Soluble Drugs. Int J Pharm Sci Nanotech. 2019; 12:4421-40.
45. M.R. Gasco, Method for producing solid lipid microspheres having a narrow size distribution. United States Patent, 1993, USS 188837.
46. Gohla SH, Dingler A. Scaling up feasibility of the production of solid lipid nanoparticles (SLN™). Pharmazie, 2001; 56:61–3.
47. Müller RH, Keck CM. Challenges and solutions for the delivery of biotech drugs – a review of drug nanocrystal technology and lipid nanoparticles. J Biotech, 2004; 113:151–70.
48. Arun Butreddy, Narendar Dudhipala and Kishan Veerabrahma. Development of olmesartanmedoxomil lipid based nanoparticles and nanosuspension: Preparation, characterization and comparative pharmacokinetic evaluation. Artificial cells, nanomed and biotech, 2018; 46(1):126-137.
49. Mehnert, W., Mäder, K. Solid lipid nanoparticles production, characterization and applications. Adv Drug Deliv Rev. 2012; 64:83-101.
50. Yang S, Zhu J, Lu Y, et al. Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharm Res, 1999b; 16:751–57.
51. Yang S, Zhu J, Lu Y, et al. Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharm Res, 1999b; 16:751–57.
52. Müller, R.H., Mäder, K., Gohla, S. Solid lipid nanoparticles (SLN) for controlled drug delivery a review of the state of the art. Eur J Pharm Biopharm. 2000; 50:161-177.
53. Siekmann B, Westesen K. Submicron-sized parenteral carrier systems based on solid lipids. Pharm Pharmacol Lett, 1992; 1:123–6.
54. Sjostrom B, Bergenstahl B. Preparation of submicron drug particles in lecithin-stabilized o/w emulsions I. Model studies of the precipitation of cholesterylacetate. Int J Pharm, 1992; 88:53–62.
55. Schubert MA, Muller-Goyman CC. Solvent injection as a new approach for manufacturing lipid nanoparticles – evaluation of the method and process parameters. Eur J Pharm Biopharm, 2003; 55:125–31.
56. Zimmermann E, Muller RH. Electrolyte- and pH-stabilities of aqueous solid lipid nanoparticle (SLNTM) dispersions in artificial gastrointestinal media. Eur J Pharm Biopharm, 2001; 52:203–10.
57. Liu et al., Solid lipid nanopartiles for pulmonary delivery of insulin. Int J Pharm, 2008; 356:333-344.
58. Dudhipala N, Veerabrahma K. Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation. Drug delivery. 2016 Feb 12; 23(2):395-404.
59. Akshaya Tatke, Narendar Dudhipala, Karthik Yadav Janga, Sai Prachetan Balguri, BharathiAvula, Monica M. Jablonski Soumyajit Majumdar. In Situ Gel of Triamcinolone Acetonide-Loaded Solid Lipid Nanoparticles for Improved Topical Ocular Delivery: Tear Kinetics and Ocular Disposition Studies. Nanomaterials (Basel). 2018 Dec 27; 9(1). pii: E33. doi: 10.3390/nano9010033.
60. Ahmed AAY, Narendar D, Mujumdar S. Ciprofloxacin Loaded Nanostructured Lipid Carriers Incorporated into In-Situ Gels to Improve Management of Bacterial Endophthalmitis. Pharmaceutics, 2020; 12(6):572.
61. Dudhipala Narendar, and Ahmed Adel Ay. Amelioration of ketoconazole in lipid nanoparticles for enhanced antifungal activity and bioavailability through oral administration for management of fungal infections. Chemistry and Physics of Lipids 2020; 232:104953.
62. Banala, N, Tirumalesh C, Suram, D. Dudhipala, N. Zotepine loaded lipid nanoparticles for oral delivery: preparation, characterization, and in vivo pharmacokinetic studies. Fut J Pharm Sci, 2020; 6(1):37.
63. Banala N, Cernam T, Suram D, Dudhipala N. Design, development and in vivo pharmacokinetic evaluation of zotepine loaded solid lipid nanoparticles for enhanced oral bioavailability. ACTA Pharmaceutica Sciencia.
64. Schubert MA, Harms M, Muller-Goyman CC. Sructural investigations on lipid nanoparticles containing high amounts of lecithin. Eur J Pharm Sci, 2006; 27:226–36.
65. Trucillo P, Campardelli R. Production of solid lipid nanoparticles with a supercritical fluid assisted process. The Journal of Supercritical Fluids. 2019 Jan 1; 143:16-23.
66. Charcosset C, Assma Ahmed El-Harati, Hatem Fessi, A membrane contactor for the preparation of solid lipid nanoparticles. Desalination, 2006; 200:570–571.
67. Zhang S.H., Shen S.C., Chen Z., Yun J.X. Preparation of solid lipid nanoparticles in co-flowing microchannels. Chemical Engineering Journal, 2008; 144: 324–328.
68. Dodiya S, Sandip, Chavhan., Aruna, Korde., &Krutika, K. Sawant. Solid lipid nanoparticles and nanosuspension of adefovirdipivoxil for bioavailability improvement: formulation, characterization, pharmacokinetic and biodistribution studies. Drug. Dev. Ind. Pharm., 2013; 39(5):733-743.
69. Dwivedi P, Khatik R, Khandelwal K, Taneja I, Rama Raju KS, Wahajuddin, Paliwal SK, Dwivedi AK, Mishra PR. Pharmacokinetics study of arteether loaded solid lipid nanoparticles: An improved oral bioavailability in rats. International Journal of Pharmaceutics 2014; 466:321–327.
70. Hao, J., Wang, F., Wang, X., Zhang, D., YBi, Y., Gao, Y., Zhao, X., & Zhang, Q. Development and optimization of baicalin-loaded solid lipid nanoparticles prepared by coacervation method using central composite design. Eur. J. Phar. Sci., 2012; 47:497-505.
71. Narendar D, Govardhan K. Capecitabine lipid nanoparticles for anti-colon cancer activity in 1, 2-dimethylhydrazine induced colon cancer: Preparation, cytotoxic, pharmacokinetic and pathological evaluation. Drug dev Ind pharm, Eraly online, March 2018. doi: 10.1080/03639045.2018.1445264.
72. Sanjula B. Effect of poloxamer 188 on lymphatic uptake of carvedilol-loaded solid lipid nanoparticles for bioavailability enhancement. J Drug Target 2009; 17:249-56.
73. Usha Kiranmai G, Narendar Dudhipala and Veerabrahma Kishan. Preparation, characterization and in vivo evaluation of felodipine solid lipid nanoparticles to improve the oral bioavailability. International Journal of Pharmaceutical Sciences and Nanotechnology. 2015; 8(4):1-8.
74. Thirupathi G, Swetha E and Narendar D. Role of isradipine loaded solid lipid nanoparticles in the pharmacodynamic effect of isradipine in rats. Drug res, 2017; 67(03):163-169.
75. Zara GP, Bargoni A, Cavalli R, et al. Pharmacokinetics and tissue distribution of idarubicin loaded solid lipid nanoparticles after duodenal administration to rats. J Pharm Sci2002; 91:1324-33.
76. Dudhipala, Narendar, Ahmed Adel Ali Youssef, and Nagaraj Banala. Colloidal lipid nanodispersion enriched hydrogel of antifungal agent for management of fungal infections: comparative in-vitro, ex-vivo and in-vivo evaluation for oral and topical application. Chemistry and Physics of Lipids 2020: 104981.
77. Sandeep V, Narendar D, Arjun N and Kishan V. Lacidipine loaded solid lipid nanoparticles for oral delivery: Preparation, characterization and In vivo evaluation. IJPSN, 2016; 9(6):3524-30.
78. Paliwal R, Rai S, Vaidya B, et al. Effect of lipid core material on characteristics of solid lipid nanoparticles designed for oral lymphatic delivery. Nanomedicine: NBM 2009; 5:184-91.
79. Chalikwar SS, Belgamwar VS, Talele VR, Surana SJ, Patil MU. Formulation and evaluation of Nimodipine-loaded solid lipid nanoparticles delivered via lymphatic transport system.Colloids Surf B Biointerfaces. 2012; 97:109-16.
80. Dudhipala N, Veerabrahma K. Pharmacokinetic and pharmacodynamic studies of nisoldipine loaded solid lipid nanoparticles by central composite design. Drug Dev Ind Pharm. 2015. (doi:10.3109/03639045.2015.1024685).
81. Narendar D, Karthik Yadav J, Thirupathi G. Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation. Artificial cells, nanomed and biotech. Early online 11 April, 2018, doi.org/10.1080/21691401.2018.1465068.
82. Almeida AJ, Runge S, Muller RH. Peptide-loaded solid lipid nanoparticles (SLN): influence of production parameters. Int J Pharm 1997; 149:255-65.
83. Luo CF, Yuan M, Chen MS, et al. Pharmacokinetics, tissue distribution and relative bioavailability of puerarin solid lipid nanoparticles following oral administration. Int J Pharm 2011; 410:138-44.
84. HouLi Li, XiaoBin Zhao, YuKun Ma, GuangXiZhai, LingBing Li, HongXiang Lou. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. Journal of Controlled Release. 2009; 133(3):238–244.
85. Pandey R, Sharma S, Khuller GK. Oral solid lipid nanoparticle-based antitubercular chemotherapy. Tuberculosis 2005; 85:415-20.
86. Guguloth S, D. Narender and V. Kishan. Preparation, Characterization and In vivo Evaluation of Rosuvastatin Calcium Loaded Solid Lipid Nanoparticles. International Journal of Pharmaceutical Sciences and Nanotechnology, 2015; 8(1):2779-2785.
87. Narendar D and Kishan V. Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: pharmacokinetic and pharmacodynamic evaluation. Euro J Pharm Biopharm. 2017; 110 (1):47-57.
88. Narendar D, Thirupathi G. Neuroprotective effect of ropinirole loaded lipid nanoparticles hydrogel for Parkinson’s disease: preparation, in vitro, ex vivo, pharmacokinetic and pharmacodynamic evaluation. Pharmaceutics, 2020; 12(5):448.
89. Kushwaha AK, Vuddanda PR, Karunanidhi P, Singh SK, and Singh S. Development and Evaluation of Solid Lipid Nanoparticles of Raloxifene Hydrochloride for Enhanced Bioavailability. BioMed Research International Volume 2013 (2013), Article ID 584549, 1- 9.
90. Tiwari R, Kamla Pathak. Nanostructured lipid carrier versus solid lipid nanoparticles of simvastatin: Comparative analysis of characteristics, pharmacokinetics and tissue uptake. International Journal of Pharmaceutics, Volume 2011; 415(1–2):232–243.
91. Cavalli R, Bargoni A, Podio V, et al. Duodenal administration of solid lipid nanoparticles loaded with different percentages of tobramycin. J Pharm Sci 2003; 92:1085-95.
92. Luo Y, Chen D, Ren L, et al. Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. J Control Release 2006; 114:53-9.
93. Narendar D and Karthik yadav J. Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: Optimization, in vitro and in vivo evaluation. Drug Dev Ind Pharm, 2017; 43(7):1205-1214.
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