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2000
Volume 19, Issue 4
  • ISSN: 2667-3878
  • E-ISSN: 2667-3886

Abstract

Introduction

Type 2 Diabetes Mellitus (T2DM) is a prevalent metabolic disease significantly impacting healthcare, characterized by increased blood glucose levels from the average level due to insulin resistance or a lack of insulin production. Canagliflozin Hemihydrate (CGN) is one of the drugs of choice in the treatment of the disease. However, CGN belongs to BCS class IV making it difficult to formulate into suitable dosage form. The purpose of the present study was to systematically optimize and explore the potential of Nanostructured Lipid Carriers (NLCs) to improve the solubility and bioavailability of CGN.

Methods

The emulsification and ultrasonication methods were used for the preparation of CGN-loaded NLCs (CGN-NLCs) by employing the Box-Behnken design. The solid lipid to liquid lipid ratio (X1), surfactant concentration (X2), and sonication time (X3) were independent variables, while particle size (Y1) and entrapment efficiency (EE) (Y2) were selected as dependent variables.

Results

The optimized batch showed particle size, zeta potential, Polydispersity Index (PDI), and EE of 221.2 ± 2.25 nm, -37 mV, 0.268 ± 0.024, and 98.2 ± 1.62%. The TEM revealed a homogeneous spherical shape of CGN-NLCs. Further, the DSC and XRD studies revealed reduced crystallinity with complete encapsulation of CGN in NLCs. The drug release study in simulated intestinal fluid (pH 6.8) showed significant CGN release from CGN-NLCs compared to CGN dispersion. Further, the intestinal permeability and pharmacokinetic study showed a 1.33-fold and 3.81-fold increase in permeability and bioavailability along with improvement in Cmax, Tmax, and [AUC]0–24 as compared to CGN dispersion.

Conclusion

Thus, the prepared CGN-NLCs could be a better viable option for T2DM with improved therapeutic efficacy.

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2025-12-10

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References

  1. SaidS. HernandezG. Sodium glucose co-transporter 2 (SGLT2) inhibition with canagliflozin in type 2 diabetes mellitus.Cardiovasc. Hematol. Agents Med. Chem.201411320320610.2174/187152571103140120103032 24025022
     [Google Scholar]
  2. DavidsonJ.A. KuritzkyL. Sodium glucose co-transporter 2 inhibitors and their mechanism for improving glycemia in patients with type 2 diabetes.Postgrad. Med.20141266334810.3810/pgm.2014.10.2819 25414933
     [Google Scholar]
  3. TaharaA. TakasuT. YokonoM. ImamuraM. KurosakiE. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors in pharmacokinetics, pharmacodynamics, and pharmacologic effects.J. Pharmacol. Sci.2016130315916910.1016/j.jphs.2016.02.003 26970780
     [Google Scholar]
  4. DietrichE. PowellJ. TaylorJ. Canagliflozin: A novel treatment option for type 2 diabetes.Drug Des. Devel. Ther.201371399140810.2147/DDDT.S48937 24285921
     [Google Scholar]
  5. European Medicines AgencyAssessment report Vokanamet.2014Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/invokana
    [Google Scholar]
  6. BurjakM RozmanPT PetekB Pharmaceutical compositions comprising Canagliflozin.WO Patent 2016030502A12017
  7. O’DriscollC.M. GriffinB.T. Biopharmaceutical challenges associated with drugs with low aqueous solubility—The potential impact of lipid-based formulations.Adv. Drug Deliv. Rev.200860661762410.1016/j.addr.2007.10.012 18155800
     [Google Scholar]
  8. AungstB.J. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism.J. Pharm. Sci.1993821097998710.1002/jps.2600821008 8254497
     [Google Scholar]
  9. ShresthaH. BalaR. AroraS. Lipid-based drug delivery systems.J. Pharm. (Cairo)2014201411010.1155/2014/801820 26556202
     [Google Scholar]
  10. DasS. Lipid-based nanoformulations for active delivery.Curr. Pharm. Biotechnol.201516428929010.2174/138920101604150218095039 25697367
     [Google Scholar]
  11. AttamaA.A. SLN, NLC, LDC: State of the art in drug and active delivery.Recent Pat. Drug Deliv. Formul.20115317818710.2174/187221111797200524 21834777
     [Google Scholar]
  12. BuszelloK. HarnischS. MüllerR.H. MüllerB.W. The influence of alkali fatty acids on the properties and the stability of parenteral O/W emulsions modified with Solutol HS 15®.Eur. J. Pharm. Biopharm.200049214314910.1016/S0939‑6411(99)00081‑8 10704897
     [Google Scholar]
  13. DoktorovovaS. SoutoE.B. Nanostructured lipid carrier-based hydrogel formulations for drug delivery: A comprehensive review.Expert Opin. Drug Deliv.20096216517610.1517/17425240802712590 19239388
     [Google Scholar]
  14. MuchowM. MaincentP. MüllerR.H. Lipid nanoparticles with a solid matrix (SLN, NLC, LDC) for oral drug delivery.Drug Dev. Ind. Pharm.200834121394140510.1080/03639040802130061 18665980
     [Google Scholar]
  15. UnerM. YenerG. Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives.Int. J. Nanomedicine200723289300 18019829
     [Google Scholar]
  16. IqbalM.A. MdS. SahniJ.K. BabootaS. DangS. AliJ. Nanostructured lipid carriers system: Recent advances in drug delivery.J. Drug Target.2012201081383010.3109/1061186X.2012.716845 22931500
     [Google Scholar]
  17. ParkS.J. GarciaC.V. ShinG.H. KimJ.T. Improvement of curcuminoid bioaccessibility from turmeric by a nanostructured lipid carrier system.Food Chem.2018251515710.1016/j.foodchem.2018.01.071 29426423
     [Google Scholar]
  18. IrbyD. DuC. LiF. Lipid–drug conjugate for enhancing drug delivery.Mol. Pharm.20171451325133810.1021/acs.molpharmaceut.6b01027 28080053
     [Google Scholar]
  19. BeloquiA. SolinísM.Á. Rodríguez-GascónA. AlmeidaA.J. PréatV. Nanostructured lipid carriers: Promising drug delivery systems for future clinics.Nanomedicine201612114316110.1016/j.nano.2015.09.004 26410277
     [Google Scholar]
  20. ApteS. Selecting surfactants for the maximum inhibition of the activity of the multidrug resistance efflux pump transporter, P-glycoprotein: Conceptual development.J. Excip. Food Chem.201015159
     [Google Scholar]
  21. VarshosazJ. EskandariS. MinaiyanM. TabbakhianM. Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: In vivo pharmacodynamic studies using rat electroshock model.Int. J. Nanomedicine2011636337110.2147/IJN.S15881 21499426
     [Google Scholar]
  22. NegiL.M. JaggiM. TalegaonkarS. Development of protocol for screening the formulation components and the assessment of common quality problems of nano-structured lipid carriers.Int. J. Pharm.20144611-240341010.1016/j.ijpharm.2013.12.006 24345574
     [Google Scholar]
  23. JahanS. AqilM. AhadA. ImamS.S. WaheedA. QadirA. Nanostructured lipid carrier for transdermal gliclazide delivery: Development and optimization by Box-Behnken design.Inorganic Nano-Metal Chem202254A11410.1080/24701556.2021.2025097
     [Google Scholar]
  24. LiuC.H. WuC.T. Optimization of nanostructured lipid carriers for lutein delivery.Colloids Surf. A Physicochem. Eng. Asp.20103532-314915610.1016/j.colsurfa.2009.11.006
     [Google Scholar]
  25. DevineniD. CurtinC.R. PolidoriD. Pharmacokinetics and pharmacodynamics of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in subjects with type 2 diabetes mellitus.J. Clin. Pharmacol.201353660161010.1002/jcph.88 23670707
     [Google Scholar]
  26. MüllerR.H. MäderK. GohlaS. Solid lipid nanoparticles (SLN) for controlled drug delivery: A review of the state of the art.Eur. J. Pharm. Biopharm.200050116117710.1016/S0939‑6411(00)00087‑4 10840199
     [Google Scholar]
  27. KasongoW.A. PardeikeJ. MüllerR.H. WalkerR.B. Selection and characterization of suitable lipid excipients for use in the manufacture of didanosine-loaded solid lipid nanoparticles and nanostructured lipid carriers.J. Pharm. Sci.2011100125185519610.1002/jps.22711 22020815
     [Google Scholar]
  28. TamjidiF. ShahediM. VarshosazJ. NasirpourA. Design and characterization of astaxanthin-loaded nanostructured lipid carriers.Innov. Food Sci. Emerg. Technol.20142636637410.1016/j.ifset.2014.06.012
     [Google Scholar]
  29. SinghA. NeupaneY.R. ManglaB. KohliK. Nanostructured lipid carriers for oral bioavailability enhancement of exemestane: Formulation design, in vitro, ex vivo, and in vivo studies.J. Pharm. Sci.2019108103382339510.1016/j.xphs.2019.06.003 31201904
     [Google Scholar]
  30. TengZ. YuM. DingY. Preparation and characterization of nimodipine-loaded nanostructured lipid systems for enhanced solubility and bioavailability.Int. J. Nanomedicine20181411913310.2147/IJN.S186899 30613141
     [Google Scholar]
  31. Ajiboye Adejumoke Lara NandiU. GalliM. TrivediV. Olanzapine loaded nanostructured lipid carriers via high shear homogenization and ultrasonication.Sci. Pharm.20218922510.3390/scipharm89020025
     [Google Scholar]
  32. RizwanullahM. AminS. AhmadJ. Improved pharmacokinetics and antihyperlipidemic efficacy of rosuvastatin-loaded nanostructured lipid carriers.J. Drug Target.2017251587410.1080/1061186X.2016.1191080 27186665
     [Google Scholar]
  33. PatelP. PatelM. Enhanced oral bioavailability of nintedanib esylate with nanostructured lipid carriers by lymphatic targeting: In vitro, cell line and in vivo evaluation.Eur. J. Pharm. Sci.202115910571510.1016/j.ejps.2021.105715 33453388
     [Google Scholar]
  34. ZhangT. ChenJ. ZhangY. ShenQ. PanW. Characterization and evaluation of nanostructured lipid carrier as a vehicle for oral delivery of etoposide.Eur. J. Pharm. Sci.201143317417910.1016/j.ejps.2011.04.005 21530654
     [Google Scholar]
  35. ChellampillaiB. KashidS. PawarA. MaliA. Investigation of dimyristoyl phosphatidyl glycerol and cholesterol based nanocochleates as a potential oral delivery carrier for methotrexate.J. Liposome Res.202232430831610.1080/08982104.2021.2018603 34957892
     [Google Scholar]
  36. ThapaC. AhadA. AqilM. ImamS.S. SultanaY. Formulation and optimization of nanostructured lipid carriers to enhance oral bioavailability of telmisartan using Box–Behnken design.J. Drug Deliv. Sci. Technol.20184443143910.1016/j.jddst.2018.02.003
     [Google Scholar]
  37. YostawonkulJ. SurassmoS. IemprideeT. Surface modification of nanostructure lipid carrier (NLC) by oleoyl-quaternized-chitosan as a mucoadhesive nanocarrier.Colloids Surf. B Biointerfaces201714930131110.1016/j.colsurfb.2016.09.049 27780087
     [Google Scholar]
  38. ChanbureeS. TiyaboonchaiW. Mucoadhesive nanostructured lipid carriers (NLCs) as potential carriers for improving oral delivery of curcumin.Drug Dev. Ind. Pharm.201743343244010.1080/03639045.2016.1257020 27808665
     [Google Scholar]
  39. WankhedeH. PenumakaS.M. MandalZ.D. Artesunate loaded bilosomes with enhanced oral bioavailability: In silico and in vitro study against Leishmania donovani promastigotes for the treatment of visceral leishmaniasis.SSRN496309910.2139/ssrn.4963099
     [Google Scholar]
  40. HassanT.H.H.A. Formulation and evaluation of self-nanoemulsifying tablets for the delivery of poorly water-soluble drugs.University and State Library of Saxony-Anhalt2015
     [Google Scholar]
  41. KumarP. KhatakS. Formulation development and characterization of Nadifloxacin loaded solid lipid nanoparticle-based hydrogel.Int Res J Pharm2021124233310.7897/2230‑8407.1204130
     [Google Scholar]
  42. MaliA.J. PawarA.P. BothirajaC. Improved lung delivery of budesonide from biopolymer based dry powder inhaler through natural inhalation of rat.Mater. Technol.201429635035710.1179/1753555714Y.0000000163
     [Google Scholar]
  43. DeshpandeA.A. Characterization and evaluation of paclitaxel loaded solid lipid nanoparticles prepared by temperature modulated solidification technique.MS thesis University of Toledo2015
     [Google Scholar]
  44. KaithwasV. DoraC.P. KushwahV. JainS. Nanostructured lipid carriers of olmesartan medoxomil with enhanced oral bioavailability.Colloids Surf. B Biointerfaces2017154102010.1016/j.colsurfb.2017.03.006 28284054
     [Google Scholar]
  45. RavindraN. Development and characterization of linezolid loaded biocompatible solid lipid based nanocarrier for enhanced lung deposition and anti-tubercular activity: Next generation tailor made carrier for dry powder inhaler.Curr Ind Sci2023111110.2174/2210299X01666230508103042
     [Google Scholar]
  46. KawishS.M. AhmedS. GullA. Development of nabumetone loaded lipid nano-scaffold for the effective oral delivery; optimization, characterization, drug release and pharmacodynamic study.J. Mol. Liq.201723151452210.1016/j.molliq.2017.01.107
     [Google Scholar]
  47. MaliA.J. RokadeA. KambleR. PawarA. BothirajaC. Resveratrol-loaded microsponge as a novel biodegradable carrier for dry powder inhaler: A new strategy in lung delivery.Bionanoscience2021111324310.1007/s12668‑020‑00800‑7
     [Google Scholar]
  48. Cirri Marzia MenniniM. MaestrelliF. Development and in vivo evaluation of an innovative “Hydrochlorothiazide-in cyclodextrins-in solid lipid nanoparticles” formulation with sustained release and enhanced oral bioavailability for potential hypertension treatment in pediatrics.Int. J. Pharm.2017521738310.1016/j.ijpharm.2017.02.022
     [Google Scholar]
  49. Neupane Yub Raj SrivastavaM AhmadN Lipid based nanocarrier system for the potential oral delivery of decitabine: formulation design, characterization, ex vivo, and in vivo assessment.Int. J. Pharm.201447760110.1016/j.ijpharm.2014.11.001
     [Google Scholar]
  50. Ahmad Javed Mir SR KohliK. Solid‐nanoemulsion preconcentrate for oral delivery of paclitaxel: Formulation design, biodistribution, and γ scintigraphy imaging.BioMed Res. Int.2014201498475610.1155/2014/984756
     [Google Scholar]
  51. ZhangH. ChenW. ZhaoZ. Lyophilized nanosuspensions for oral bioavailability improvement of insoluble drugs: Preparation, characterization, and pharmacokinetic studies.J. Pharm. Innov.201712327128010.1007/s12247‑017‑9287‑8
     [Google Scholar]
  52. MehnertW. MäderK. Solid lipid nanoparticles production, characterization and applications.Adv. Drug Deliv. Rev.2001472-316519610.1016/S0169‑409X(01)00105‑3 11311991
     [Google Scholar]
  53. NevesA.R. QueirozJ.F. ReisS. Brain-targeted delivery of resveratrol using solid lipid nanoparticles functionalized with apolipoprotein E.J. Nanobiotechnology20161412710.1186/s12951‑016‑0177‑x 27061902
     [Google Scholar]
  54. MaliA.J. JoshiP.A. BothirajaC. PawarA.P. Fabrication and application of dimyristoyl phosphatidylcholine biomaterial-based nanocochleates dry powder inhaler for controlled release resveratrol delivery.Future J. Pharm. Sci.2021714710.1186/s43094‑021‑00189‑4
     [Google Scholar]
  55. PawarJ. TayadeA. GangurdeA.B. MoravkarK.K. AminP.D. Solubility and dissolution enhancement of efavirenz hot melt extruded amorphous solid dispersions using combination of polymeric blends: A QbD approach.Eur. J. Pharm. Sci.201688378910.1016/j.ejps.2016.04.001
     [Google Scholar]
  56. JaywantN. DesaiP.R. MoravkarK.K. KhannaD.K. AminP.D. Exploring the potential of porous silicas as a carrier system for dissolution rate enhancement of artemether.Asian J. Pharm. Sci.201611676010.1016/j.ajps.2016.06.002
     [Google Scholar]
  57. Kumar PandaB. ChellampillaiB. GhodkeS. MaliA. KambleR. Investigation of magnesium aluminometasilicate (Neusilin US2) based surface solid dispersion of sorafenib tosylate using QbD approach: In vitro and in vivo pharmacokinetic study.ADMET DMPK202412468770210.5599/admet.2338 39473622
     [Google Scholar]
  58. ZafarA. AlruwailiN.K. ImamS.S. Formulation of chitosan-coated piperine NLCs: Optimization, in vitro characterization, and in vivo preclinical assessment.AAPS PharmSciTech202122723110.1208/s12249‑021‑02098‑4 34477999
     [Google Scholar]
  59. ManglaB. NeupaneY.R. SinghA. KumarP. ShafiS. KohliK. Lipid-nanopotentiated combinatorial delivery of tamoxifen and sulforaphane: Ex vivo, in vivo and toxicity studies.Nanomedicine (Lond.)202015262563258310.2217/nnm‑2020‑0277 33079004
     [Google Scholar]
  60. Reddy Gouru Santhosh Patel Sonam Krishna Veni Nagappan development and validation of reverse phase high performance liquid chromatography method for the estimation of canagliflozin in bulk and its pharmaceutical formulation.J. Young Pharmacists202012432132610.5530/jyp.2020.12.85
     [Google Scholar]
  61. PatilS. BahadureS. PatilS. Formulation of canagliflozin hemihydrate-loaded bilosomes for the treatment of Type-2 diabetes mellitus: In vitro, in vivo and in silico molecular docking studies.J Drug Deliv Technol20238610463010.1016/j.jddst.2023.104630
     [Google Scholar]
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Formulation and Evaluation of Canagliflozin Hemihydrate-loaded Nanostructured Lipid Carriers Using Box-Behnken Design: Physicochemical Characterization, Ex-vivo Analysis, and In-vivo Pharmacokinetics
Recent Advances in Drug Delivery and Formulation 19, 371 (2025); https://doi.org/10.2174/0126673878343297250325060051
/content/journals/raddf/10.2174/0126673878343297250325060051
/content/journals/raddf/10.2174/0126673878343297250325060051
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  • Article Type:     Research Article
Keyword(s): bioavailability; Box-Behnken design; Canagliflozin hemihydrate; ex-vivo permeability; in-vitro release; nanostructured lipid carriers

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