Skip to content
2000
Volume 31, Issue 5
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Introduction

Glyburide is a drug for the treatment of diabetes mellitus and has a potential effect on Alzheimer's disease. It is also a BCS Class II drug with low solubility and low permeability. Developing a nanosuspension formulation and increasing the solubility and dissolution rate of glyburide is required to overcome this challenge.

Methods

Thus, the goal of this work was to create glyburide nanosuspensions by ball milling and homogenizing glyburide to increase its solubility and rate of dissolution. To achieve this, the nanosuspension formulation was optimized using a central composite design. Zeta potential, particle size distribution and solubility were selected by way of dependent variables, and ball milling time, homogenization cycles, and Pluronic F-127/glyburide ratio were chosen as independent variables. Glyburide nanosuspensions were obtained with a particle size of 244.6 ± 2.685 nm. release and solubility studies were conducted following optimization.

Results

The saturation solubility of glyburide was nearly doubled as a result of the nanocrystal formation. X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and fourier-transform infrared spectroscopy (FT-IR) were used to assess the nanosuspension. SEM images confirmed that the nanocrystal formation process was successful. Glyburide and the excipients have no incompatibilities, their physical states have not changed, and the preparation method has not affected the stability of glyburide, according to DCS, XRD, and FT-IR analyses.

Conclusion

These studies indicated that a combination of ball milling and homogenization techniques significantly enhanced the solubility of glyburide and its release from the formulation. Consequently, this approach can be applied to formulations characterized by low absorption and limited bioavailability.

Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128321501240828054050
2024-09-20
2025-04-16
Loading full text...

Full text loading...

References

  1. FengY. HeH. LiF. LuY. QiJ. WuW. An update on the role of nanovehicles in nose-to-brain drug delivery.Drug Discov. Today20182351079108810.1016/j.drudis.2018.01.005 29330120
    [Google Scholar]
  2. FurquanA. HafeezA. RahmanM.A. Brain targeting of drugs via intranasal route in conjunction with nanoparticle-based systems: An updated review.J. Nanopart. Res.2023251123310.1007/s11051‑023‑05880‑6
    [Google Scholar]
  3. Yeşilkır-BaydarS. The shortest way to treatment of Alzheimer's disease: Intranasal approaches.Multidisciplinary research in health sciences.2020575593 https://www.researchgate.net/publication/352455472_ALZHEIMER_HASTALIGI_TEDAVISI_ICIN_EN_KESTIRME_YOL_INTRANAZAL_YAKLASIMLAR
    [Google Scholar]
  4. TalegaonkarS. MishraP.R. Intranasal delivery: An approach to bypass the blood brain barrier.Indian J. Pharmacol.2004363140147
    [Google Scholar]
  5. AlexanderA. AgrawalM. UddinA. Recent expansions of novel strategies towards the drug targeting into the brain.Int. J. Nanomedicine2019145895590910.2147/IJN.S210876 31440051
    [Google Scholar]
  6. KapoorM. CloydJ.C. SiegelR.A. A review of intranasal formulations for the treatment of seizure emergencies.J. Control. Release201623714715910.1016/j.jconrel.2016.07.001 27397490
    [Google Scholar]
  7. PatelA. SurtiN. MahajanA. Intranasal drug delivery: Novel delivery route for effective management of neurological disorders.J. Drug Deliv. Sci. Technol.20195213013710.1016/j.jddst.2019.04.017
    [Google Scholar]
  8. KumarN.N. GautamM. LochheadJ.J. Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: Implications for nasal physiology and drug delivery.Sci. Rep.2016613173210.1038/srep31732 27558973
    [Google Scholar]
  9. LochheadJ.J. WolakD.J. PizzoM.E. ThorneR.G. Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration.J. Cereb. Blood Flow Metab.201535337138110.1038/jcbfm.2014.215 25492117
    [Google Scholar]
  10. IllumL. Transport of drugs from the nasal cavity to the central nervous system.Eur. J. Pharm. Sci.200011111810.1016/S0928‑0987(00)00087‑7 10913748
    [Google Scholar]
  11. CroweT.P. GreenleeM.H.W. KanthasamyA.G. HsuW.H. Mechanism of intranasal drug delivery directly to the brain.Life Sci.2018195445210.1016/j.lfs.2017.12.025 29277310
    [Google Scholar]
  12. KnopmanD.S. AmievaH. PetersenR.C. Alzheimer disease.Nat. Rev. Dis. Primers2021713310.1038/s41572‑021‑00269‑y 33986301
    [Google Scholar]
  13. FonsecaL.C. LopesJ.A. VieiraJ. Intranasal drug delivery for treatment of Alzheimer’s disease.Drug Deliv. Transl. Res.202111241142510.1007/s13346‑021‑00940‑7 33638130
    [Google Scholar]
  14. RabieeN. AhmadiS. AfshariR. Polymeric nanoparticles for nasal drug delivery to the brain: Relevance to Alzheimer’s disease.Adv. Ther. (Weinh.)202143200007610.1002/adtp.202000076
    [Google Scholar]
  15. Taléns-ViscontiR. de Julián-OrtizJ.V. Vila-BusóO. Diez-SalesO. NácherA. Intranasal drug administration in Alzheimer-type dementia: Towards clinical applications.Pharmaceutics2023155139910.3390/pharmaceutics15051399 37242641
    [Google Scholar]
  16. DigheS. JogS. MominM. SawarkarS. OmriA. Intranasal drug delivery by nanotechnology: Advances in and challenges for Alzheimer’s disease management.Pharmaceutics20231615810.3390/pharmaceutics16010058 38258068
    [Google Scholar]
  17. KandimallaR. ThirumalaV. ReddyP.H. Is Alzheimer’s disease a Type 3 diabetes? A critical appraisal.Biochim. Biophys. Acta Mol. Basis Dis.2017186351078108910.1016/j.bbadis.2016.08.018 27567931
    [Google Scholar]
  18. Di StefanoA. IannitelliA. LaserraS. SozioP. Drug delivery strategies for Alzheimer’s disease treatment.Expert Opin. Drug Deliv.20118558160310.1517/17425247.2011.561311 21391862
    [Google Scholar]
  19. MoreiraP.I. Alzheimer’s disease and diabetes: An integrative view of the role of mitochondria, oxidative stress, and insulin.J. Alzheimers Dis.201230s2S199S21510.3233/JAD‑2011‑111127 22269163
    [Google Scholar]
  20. DeshmukhC.D. Diabetes mellitus- A review.Int J Pure Appl Biosci201533224230
    [Google Scholar]
  21. AhtiluotoS. PolvikoskiT. PeltonenM. Diabetes, Alzheimer disease, and vascular dementia.Neurology201075131195120210.1212/WNL.0b013e3181f4d7f8 20739645
    [Google Scholar]
  22. FemminellaG.D. BencivengaL. PetragliaL. Antidiabetic drugs in Alzheimer’s disease: Mechanisms of action and future perspectives.J. Diabetes Res.201720171710.1155/2017/7420796 28656154
    [Google Scholar]
  23. S Roriz-Filho J, Sá-Roriz TM, Rosset I, et al. (Pre)diabetes, brain aging, and cognition.Biochim. Biophys. Acta20091792543244310.1016/j.bbadis.2008.12.003 19135149
    [Google Scholar]
  24. de la MonteS.M. Type 3 diabetes is sporadic Alzheimer’s disease: Mini-review.Eur. Neuropsychopharmacol.201424121954196010.1016/j.euroneuro.2014.06.008 25088942
    [Google Scholar]
  25. RizviS.M. ShaikhS. WaseemS.M. Role of anti-diabetic drugs as therapeutic agents in Alzheimer’s disease.EXCLI J.201514684696 27152105
    [Google Scholar]
  26. AtmacaM.H. EcemişG.C. Oral antidiyabetik ajanlar.J. Exp. Clin. Med.201229s1s23s2910.5835/jecm.omu.29.s1.006
    [Google Scholar]
  27. MalekR. DavisS.N. Pharmacokinetics, efficacy and safety of glyburide for treatment of gestational diabetes mellitus.Expert Opin. Drug Metab. Toxicol.201612669169910.1080/17425255.2016.1187131 27163280
    [Google Scholar]
  28. WeiH. DaltonC. DimasoM. KanferI. LöbenbergR. Physicochemical characterization of five glyburide powders: A BCS based approach to predict oral absorption.Eur. J. Pharm. Biopharm.20086931046105610.1016/j.ejpb.2008.01.026 18374555
    [Google Scholar]
  29. HasaD. Drug nanocrystals: Theoretical background of solubility increase and dissolution rate enhancement.Chem. Biochem. Eng. Q.201428324725810.15255/CABEQ.2013.1835
    [Google Scholar]
  30. PeltonenL. HirvonenJ. Drug nanocrystals - Versatile option for formulation of poorly soluble materials.Int. J. Pharm.20185371-2738310.1016/j.ijpharm.2017.12.005 29262301
    [Google Scholar]
  31. ZhangJ. XieZ. ZhangN. ZhongJ. Nanosuspension drug delivery system: Preparation, characterization, postproduction processing,dosage form, and application. In: Nanostructures for Drug Delivery.20174134310.1016/B978‑0‑323‑46143‑6.00013‑0
    [Google Scholar]
  32. GulsunT. BornaS.E. VuralI. SahinS. Preparation and characterization of furosemide nanosuspensions.J. Drug Deliv. Sci. Technol.2018459310010.1016/j.jddst.2018.03.005
    [Google Scholar]
  33. HongC. DangY. LinG. Effects of stabilizing agents on the development of myricetin nanosuspension and its characterization: An in vitro and in vivo evaluation.Int. J. Pharm.20144771-225126010.1016/j.ijpharm.2014.10.044 25445518
    [Google Scholar]
  34. WangY. ZhengY. ZhangL. WangQ. ZhangD. Stability of nanosuspensions in drug delivery.J. Control. Release201317231126114110.1016/j.jconrel.2013.08.006 23954372
    [Google Scholar]
  35. ImonoM. UchiyamaH. YoshidaS. The elucidation of key factors for oral absorption enhancement of nanocrystal formulations: In vitro-in vivo correlation of nanocrystals.Eur. J. Pharm. Biopharm.2020146849210.1016/j.ejpb.2019.12.002 31816392
    [Google Scholar]
  36. AgrawalY.K. PatelV.R. Nanosuspension: An approach to enhance solubility of drugs.J. Adv. Pharm. Technol. Res.201122818710.4103/2231‑4040.82950 22171298
    [Google Scholar]
  37. YadavG.V. SinghS.R. Nanosuspension: A promising drug delivery system.Pharmacophore20123217243
    [Google Scholar]
  38. LiJ. FuQ. LiuX. LiM. WangY. Formulation of nimodipine nanocrystals for oral administration.Arch. Pharm. Res.201639220221210.1007/s12272‑015‑0685‑5 26584914
    [Google Scholar]
  39. KarakucukA. CelebiN. TeksinZ.S. Preparation of ritonavir nanosuspensions by microfluidization using polymeric stabilizers: I. A Design of Experiment approach.Eur. J. Pharm. Sci.20169511112110.1016/j.ejps.2016.05.010 27181836
    [Google Scholar]
  40. AkdagY. Nanoparticle-containing lyophilized dry powder inhaler formulations optimized using central composite design with improved aerodynamic parameters and redispersibility.Pharm. Dev. Technol.202328112413710.1080/10837450.2023.2166066 36602194
    [Google Scholar]
  41. PabariR.M. RamtoolaZ. Application of face centred central composite design to optimise compression force and tablet diameter for the formulation of mechanically strong and fast disintegrating orodispersible tablets.Int. J. Pharm.20124301-2182510.1016/j.ijpharm.2012.03.021 22465631
    [Google Scholar]
  42. AlamS. MustafaG. KhanZ.I. Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: A pharmacoscintigraphic study.Int. J. Nanomedicine201275705571810.2147/IJN.S35329 23180965
    [Google Scholar]
  43. KarakucukA. CanpinarH. CelebiN. Ritonavir nanosuspensions prepared by microfluidization with enhanced solubility and desirable immunological properties.Pharm. Dev. Technol.202227101027103710.1080/10837450.2022.2145309 36343117
    [Google Scholar]
  44. BhanderiM. ShahJ. GorainB. Optimized rivastigmine nanoparticles coated with eudragit for intranasal application to brain delivery: Evaluation and nasal ciliotoxicity studies.Materials (Basel)20211421629110.3390/ma14216291 34771817
    [Google Scholar]
  45. KakadS.P. GangurdeT.D. KshirsagarS.J. MundheV.G. Nose to brain delivery of nanosuspensions with first line antiviral agents is alternative treatment option to Neuro-AIDS treatment.Heliyon202287e0992510.1016/j.heliyon.2022.e09925 35879999
    [Google Scholar]
  46. IbrahimM.A. ShazlyG.A. AleanizyF.S. AlqahtaniF.Y. ElosailyG.M. Formulation and evaluation of docetaxel nanosuspensions: In vitro evaluation and cytotoxicity.Saudi Pharm. J.2019271495510.1016/j.jsps.2018.07.018 30662306
    [Google Scholar]
  47. KaplanM. ÖztürkK. ÖztürkS.C. TavukçuoğluE. EsendağlıG. CalisS. Effects of particle geometry for PLGA-based nanoparticles: Preparation and in vitro/in vivo evaluation.Pharmaceutics202315117510.3390/pharmaceutics15010175 36678804
    [Google Scholar]
  48. U.S. Pharmacopoeial Convention. The United States Pharmacopoeia, 30th Rev., Rockville, MD,2006
    [Google Scholar]
  49. ArslanA. YetB. NemutluE. Akdağ ÇaylıY. EroğluH. ÖnerL. Celecoxib nanoformulations with enhanced solubility, dissolution rate, and oral bioavailability: Experimental approaches over in vitro/in vivo evaluation.Pharmaceutics202315236310.3390/pharmaceutics15020363 36839685
    [Google Scholar]
  50. SingareD.S. MarellaS. GowthamrajanK. KulkarniG.T. VooturiR. RaoP.S. Optimization of formulation and process variable of nanosuspension: An industrial perspective.Int. J. Pharm.20104021-221322010.1016/j.ijpharm.2010.09.041 20933066
    [Google Scholar]
  51. ElmowafyM. ShalabyK. Al-SaneaM.M. Influence of stabilizer on the development of luteolin nanosuspension for cutaneous delivery: An in vitro and in vivo evaluation.Pharmaceutics20211311181210.3390/pharmaceutics13111812 34834227
    [Google Scholar]
  52. PaillaS.R. TalluriS. RangarajN. Intranasal zotepine nanosuspension: Intended for improved brain distribution in rats.Daru201927254155610.1007/s40199‑019‑00281‑4 31256410
    [Google Scholar]
  53. DengJ. HuangL. LiuF. Understanding the structure and stability of paclitaxel nanocrystals.Int. J. Pharm.2010390224224910.1016/j.ijpharm.2010.02.013 20167270
    [Google Scholar]
  54. WangH. PanQ. RempelG.L. Micellar nucleation differential microemulsion polymerization.Eur. Polym. J.201147597398010.1016/j.eurpolymj.2010.11.009
    [Google Scholar]
  55. HemarY. HorneD.S. A diffusing wave spectroscopy study of the kinetics of Ostwald ripening in protein-stabilised oil/water emulsions.Colloids Surf. B Biointerfaces1999123-623924610.1016/S0927‑7765(98)00079‑4
    [Google Scholar]
  56. GaoY. LiZ. SunM. Preparation, characterization, pharmacokinetics, and tissue distribution of curcumin nanosuspension with TPGS as stabilizer.Drug Dev. Ind. Pharm.201036101225123410.3109/03639041003695139 20545506
    [Google Scholar]
  57. SeverinoP. AlmeidaT. BarbosaT.C. Ibuprofen nanocrystals: Production, lyophilization and release profile.IJAMB202034347
    [Google Scholar]
  58. MaY.Q. ZhangZ.Z. LiG. ZhangJ. XiaoH.Y. LiX.F. Solidification drug nanosuspensions into nanocrystals by freeze-drying: A case study with ursodeoxycholic acid.Pharm. Dev. Technol.201621218018810.3109/10837450.2014.982822 25427602
    [Google Scholar]
  59. TeeranachaideekulV. JunyaprasertV.B. SoutoE.B. MüllerR.H. Development of ascorbyl palmitate nanocrystals applying the nanosuspension technology.Int. J. Pharm.20083541-222723410.1016/j.ijpharm.2007.11.062 18242898
    [Google Scholar]
  60. AmbrusR. AlshweiatA. Szabó-RévészP. BartosC. CsókaI. Smartcrystals for efficient dissolution of poorly water-soluble meloxicam.Pharmaceutics202214224510.3390/pharmaceutics14020245 35213978
    [Google Scholar]
  61. AmisT.M. RenukuntlaJ. BollaP.K. ClarkB.A. Selection of cryoprotectant in lyophilization of progesterone-loaded stearic acid solid lipid nanoparticles.Pharmaceutics202012989210.3390/pharmaceutics12090892 32961738
    [Google Scholar]
  62. LayreA.M. CouvreurP. RichardJ. RequierD. Eddine GhermaniN. GrefR. Freeze-drying of composite core-shell nanoparticles.Drug Dev. Ind. Pharm.200632783984610.1080/03639040600685134 16908421
    [Google Scholar]
  63. YadollahiR. VasilevK. SimovicS. Nanosuspension technologies for delivery of poorly soluble drugs.J. Nanomater.2015201511310.1155/2015/216375
    [Google Scholar]
  64. WangL. HaoY. LiuN. MaM. YinZ. ZhangX. Enhance the dissolution rate and oral bioavailability of pranlukast by preparing nanosuspensions with high-pressure homogenizing method.Drug Dev. Ind. Pharm.201238111381138910.3109/03639045.2011.652636 22300415
    [Google Scholar]
  65. AliH.S.M. YorkP. AliA.M.A. BlagdenN. Hydrocortisone nanosuspensions for ophthalmic delivery: A comparative study between microfluidic nanoprecipitation and wet milling.J. Control. Release2011149217518110.1016/j.jconrel.2010.10.007 20946923
    [Google Scholar]
  66. LakshmiP. KumarG.A. Nanosuspension technology: A review.Int. J. Pharm. Pharm. Sci.201023540
    [Google Scholar]
  67. BartosC. Jójárt-LaczkovichO. KatonaG. Optimization of a combined wet milling process in order to produce poly(vinyl alcohol) stabilized nanosuspension.Drug Des. Devel. Ther.2018121567158010.2147/DDDT.S159965 29910603
    [Google Scholar]
  68. LiJ. WangZ. ZhangH. GaoJ. ZhengA. Progress in the development of stabilization strategies for nanocrystal preparations.Drug Deliv.2021281193610.1080/10717544.2020.1856224 33336609
    [Google Scholar]
  69. GaoL. LiuG. WangX. LiuF. XuY. MaJ. Preparation of a chemically stable quercetin formulation using nanosuspension technology.Int. J. Pharm.20114041-223123710.1016/j.ijpharm.2010.11.009 21093559
    [Google Scholar]
  70. JacobsC. MüllerR.H. Production and characterization of a budesonide nanosuspension for pulmonary administration.Pharm. Res.200219218919410.1023/A:1014276917363 11883646
    [Google Scholar]
  71. AliH.S.M. HanafyA. AlqurshiA. Engineering of solidified glyburide nanocrystals for tablet formulation via loading of carriers: Downstream processing, characterization, and bioavailability.Int. J. Nanomedicine2019141893190610.2147/IJN.S194734 30936692
    [Google Scholar]
  72. RachmawatiH. ShaalL.A. MüllerR.H. KeckC.M. Development of curcumin nanocrystal: Physical aspects.J. Pharm. Sci.2013102120421410.1002/jps.23335 23047816
    [Google Scholar]
  73. GülsünT. BudakÇ. Vuralİ. SahinS. ÖnerL. Preparation and characterization of nimesulide containing nanocrystal formulations.Pharm. Dev. Technol.201318365365910.3109/10837450.2012.663390 22375930
    [Google Scholar]
  74. AlshafieeM. AljammalM.K. MarklD. Hot-melt extrusion process impact on polymer choice of glyburide solid dispersions: The effect of wettability and dissolution.Int. J. Pharm.201955924525410.1016/j.ijpharm.2019.01.038 30699365
    [Google Scholar]
  75. ShatalovaO.V. KrivandinA.V. AksenovaN.A. Solov’evaA.B. Structure of pluronic F-127 and its tetraphenylporphyrin complexes: X-ray diffraction study.Polym. Sci. Ser. A200850441742110.1134/S0965545X08040093
    [Google Scholar]
  76. AlbertiniB. PasseriniN. Di SabatinoM. Poloxamer 407 microspheres for orotransmucosal drug delivery. Part I: Formulation, manufacturing and characterization.Int. J. Pharm.20103991-2717910.1016/j.ijpharm.2010.08.004 20696227
    [Google Scholar]
  77. KakranM. SahooN.G. LiL. Fabrication of drug nanoparticles by evaporative precipitation of nanosuspension.Int. J. Pharm.20103831-228529210.1016/j.ijpharm.2009.09.030 19781606
    [Google Scholar]
  78. GulsunT. AkdagY. IzatN. CetinM. OnerL. SahinS. Development and characterization of metformin hydrochloride- and glyburide-containing orally disintegrating tablets.Pharm. Dev. Technol.2020258999100910.1080/10837450.2020.1772290 32431206
    [Google Scholar]
  79. SarnesA. KovalainenM. HäkkinenM.R. Nanocrystal-based per-oral itraconazole delivery: Superior in vitro dissolution enhancement versus Sporanox® is not realized in in vivo drug absorption.J. Control. Release201418010911610.1016/j.jconrel.2014.02.016 24566254
    [Google Scholar]
  80. Tenorio-AlfonsoA. Vázquez RamosE. MartínezI. AmbrosiM. RaudinoM. Assessment of the structures contribution (crystalline and mesophases) and mechanical properties of polycaprolactone/] pluronic blends.J. Mech. Behav. Biomed. Mater.202313910566810.1016/j.jmbbm.2023.105668 36638636
    [Google Scholar]
  81. HuangZ. StaufenbielS. BodmeierR. Combination of co-crystal and nanocrystal techniques to improve the solubility and dissolution rate of poorly soluble drugs.Pharm. Res.202239594996110.1007/s11095‑022‑03243‑9 35552985
    [Google Scholar]
  82. KeckC. MüllerR. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation.Eur. J. Pharm. Biopharm.200662131610.1016/j.ejpb.2005.05.009 16129588
    [Google Scholar]
  83. WeiL. JiY. GongW. Preparation, physical characterization and pharmacokinetic study of paclitaxel nanocrystals.Drug Dev. Ind. Pharm.20154181343135210.3109/03639045.2014.950272 25156484
    [Google Scholar]
  84. ZhangH. HollisC.P. ZhangQ. LiT. Preparation and antitumor study of camptothecin nanocrystals.Int. J. Pharm.20114151-229330010.1016/j.ijpharm.2011.05.075 21679755
    [Google Scholar]
  85. SunY. ChenD. ZhaoY. Exploitation of nanocrystal suspension as an effective oral formulation for oxfendazole.Drug Deliv. Transl. Res.20221251219122910.1007/s13346‑021‑01012‑6 34148210
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128321501240828054050
Loading
/content/journals/cpd/10.2174/0113816128321501240828054050
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test