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Volume 21, Issue 11
  • ISSN: 1567-2018
  • E-ISSN: 1875-5704

Abstract

Background

Linagliptin (LNG) exhibits poor bioavailability and numerous side effects, significantly limiting its use. Transdermal drug delivery systems (TDDS) offer a potential solution to overcome the first-pass effect and gastrointestinal reactions associated with oral formulations.

Objective

The aim of this study was to develop LNG microparticle gels to enhance drug bioavailability and mitigate side effects.

Methods

Linagliptin hyaluronic acid (LNG-HA) microparticles were prepared by spray drying method and their formulation was optimized a one-factor method. The solubility and release were investigated using the slurry method. LNG-HA microparticle gels were prepared and optimised using transdermal permeation assay. The hypoglycaemic effect of the LNG-HA microparticle gel was examined on diabetic mice.

Results

The results indicated that the LNG-HA microparticle encapsulation rate was 84.46%. Carbomer was selected as the gel matrix for the microparticle gels. Compared to the oral API, the microparticle gel formulation demonstrated a distinct biphasic release pattern. In the first 30 minutes, only 43.56% of the drug was released, followed by a gradual release. This indicates that the formulation achieved a slow-release effect from a dual reservoir system. Furthermore, pharmacodynamic studies revealed a sustained hypoglycemic effect lasting for 48 hours with the LNG microparticle gel formulation.

Conclusion

These findings signify that the LNG microparticle gel holds significant clinical value for providing sustained release and justifies its practical application.

© 2024 Bentham Science Publishers
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2024-12-01
2024-11-26

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References

  1. D, P.; Yanmanagandla, D.; Sripada, R.D. Formulation and evaluation of linagliptin mucoadhesive microspheres.Int. Res. J. Pharma.201895111710.7897/2230‑8407.09567
     [Google Scholar]
  2. Graefe-ModyU. RetlichS. FriedrichC. Clinical pharmacokinetics and pharmacodynamics of linagliptin.Clin. Pharmacokinet.201251741142710.2165/11630900‑000000000‑00000 22568694
     [Google Scholar]
  3. ShahP. ChavdaK. VyasB. PatelS. Formulation development of linagliptin solid lipid nanoparticles for oral bioavailability enhancement: role of P-gp inhibition.Drug Deliv. Transl. Res.20211131166118510.1007/s13346‑020‑00839‑9 32804301
     [Google Scholar]
  4. SaeediP. PetersohnI. SalpeaP. MalandaB. KarurangaS. UnwinN. ColagiuriS. GuariguataL. MotalaA.A. OgurtsovaK. ShawJ.E. BrightD. WilliamsR. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition.Diabetes Res. Clin. Pract.201915710784310.1016/j.diabres.2019.10784331518657
     [Google Scholar]
  5. DespotopoulouD. LagopatiN. PispasS. GazouliM. DemetzosC. PippaN. The technology of transdermal delivery nanosystems: From design and development to preclinical studies.Int. J. Pharm.202261112129010.1016/j.ijpharm.2021.121290 34788674
     [Google Scholar]
  6. CarterP. NarasimhanB. WangQ. Biocompatible nanoparticles and vesicular systems in transdermal drug delivery for various skin diseases.Int. J. Pharm.2019555496210.1016/j.ijpharm.2018.11.032 30448309
     [Google Scholar]
  7. Escobar-ChávezJ.J. Rodríguez-CruzI.M. Domínguez-DelgadoC.L. Díaz-TorresR. AléncasterN.C. Nanocarrier systems for transdermal drug delivery.Recent Advances in Novel Drug Carrier Systems.LondonIntechOpen2012
     [Google Scholar]
  8. ZhaoW. MaL. GuoS. LiuJ.Y. PiaoJ. PiaoM. Transdermal drug delivery system of domperidone sustained-release coated microsphere gels: In vitro characterization and In vivo evaluation.J. Drug Deliv. Sci. Technol.20227810393910.1016/j.jddst.2022.103939
     [Google Scholar]
  9. LaneM.E. Skin penetration enhancers.Int. J. Pharm.20134471-2122110.1016/j.ijpharm.2013.02.040 23462366
     [Google Scholar]
  10. SchoellhammerC.M. BlankschteinD. LangerR. Skin permeabilization for transdermal drug delivery: Recent advances and future prospects.Expert Opin. Drug Deliv.201411339340710.1517/17425247.2014.875528 24392787
     [Google Scholar]
  11. PegoraroC. MacNeilS. BattagliaG. Transdermal drug delivery: From micro to nano.Nanoscale2012461881189410.1039/c2nr11606e 22334401
     [Google Scholar]
  12. HadgraftJ. LaneM.E. Skin permeation: The years of enlightenment.Int. J. Pharm.20053051-221210.1016/j.ijpharm.2005.07.014 16246513
     [Google Scholar]
  13. SantosL.F. CorreiaI.J. SilvaA.S. ManoJ.F. Biomaterials for drug delivery patches.Eur. J. Pharm. Sci.2018118496610.1016/j.ejps.2018.03.020 29572160
     [Google Scholar]
  14. HoareT.R. KohaneD.S. Hydrogels in drug delivery: Progress and challenges.Polymer20084981993200710.1016/j.polymer.2008.01.027
     [Google Scholar]
  15. ShahD.K. KhandavilliS. PanchagnulaR. Alteration of skin hydration and its barrier function by vehicle and permeation enhancers: A study using TGA, FTIR, TEWL and drug permeation as markers.Methods Find. Exp. Clin. Pharmacol.200830749951210.1358/mf.2008.30.7.1159653 18985178
     [Google Scholar]
  16. PanchagnulaR. SalveP.S. ThomasN.S. JainA.K. RamaraoP. Transdermal delivery of naloxone: Effect of water, propylene glycol, ethanol and their binary combinations on permeation through rat skin.Int. J. Pharm.20012191-29510510.1016/S0378‑5173(01)00634‑2 11337170
     [Google Scholar]
  17. GuB. SunX. PapadimitrakopoulosF. BurgessD.J. Seeing is believing, PLGA microsphere degradation revealed in PLGA microsphere/PVA hydrogel composites.J. Control. Release201622817017810.1016/j.jconrel.2016.03.011 26965956
     [Google Scholar]
  18. WangJ. WangB.M. SchwendemanS.P. Characterization of the initial burst release of a model peptide from poly(d,l-lactide-co-glycolide) microspheres.J. Control. Release2002822-328930710.1016/S0168‑3659(02)00137‑2 12175744
     [Google Scholar]
  19. KangJ. SchwendemanS.P. Pore closing and opening in biodegradable polymers and their effect on the controlled release of proteins.Mol. Pharm.20074110411810.1021/mp060041n 17274668
     [Google Scholar]
  20. HuhY. ChoH.J. YoonI.S. ChoiM.K. KimJ.S. OhE. ChungS.J. ShimC.K. KimD.D. Preparation and evaluation of spray-dried hyaluronic acid microspheres for intranasal delivery of fexofenadine hydrochloride.Eur. J. Pharm. Sci.201040191510.1016/j.ejps.2010.02.002 20149868
     [Google Scholar]
  21. BrownM.B. JonesS.A. Hyaluronic acid: A unique topical vehicle for the localized delivery of drugs to the skin.J. Eur. Acad. Dermatol. Venereol.200519330831810.1111/j.1468‑3083.2004.01180.x 15857456
     [Google Scholar]
  22. ZhuJ. TangX. JiaY. HoC.T. HuangQ. Applications and delivery mechanisms of hyaluronic acid used for topical/transdermal delivery - A review.Int. J. Pharm.202057811912710.1016/j.ijpharm.2020.119127 32036009
     [Google Scholar]
  23. WooJ.S. PiaoM.G. LiD.X. RyuD.S. ChoiJ.Y. KimJ.A. KimJ.H. JinS.G. KimD.D. LyooW.S. Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability.Int. J. Pharm.2007345134141
     [Google Scholar]
  24. WuJ. Control of silk microsphere formation using polyethylene glycol (PEG).Acta Biomater.201639156168
     [Google Scholar]
  25. LiuZ. BuR. ZhaoL. LiuL. DongN. ZhangY. YinT. HeH. GouJ. TangX. Hydrogel-containing PLGA microspheres of palonosetron hydrochloride for achieving dual-depot sustained release.J. Drug Deliv. Sci. Technol.20216510277510.1016/j.jddst.2021.102775
     [Google Scholar]
  26. ThombreA. TseS. YeohT. ChenR. NorthR. BrownM. Ex vivo (human skin) and in vivo (minipig) permeation of propylene glycol applied as topical crisaborole ointment, 2%.Int. J. Pharm.202057611884710.1016/j.ijpharm.2019.118847 31759994
     [Google Scholar]
  27. ChantasartD. LiS.K. Structure enhancement relationship of chemical penetration enhancers in drug transport across the stratum corneum.Pharmaceutics201241719210.3390/pharmaceutics4010071 24300181
     [Google Scholar]
  28. WilliamsA.C. BarryB.W. Penetration enhancers.Adv. Drug Deliv. Rev.200456560361810.1016/j.addr.2003.10.025 15019749
     [Google Scholar]
  29. VenugantiV.V.K. PerumalO.P. Poly(amidoamine) dendrimers as skin penetration enhancers: Influence of charge, generation, and concentration.J. Pharm. Sci.20099872345235610.1002/jps.21603
     [Google Scholar]
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Transdermal Drug Delivery System of Linagliptin Sustained-release Microparticle Gels: In vitro Characterization and In vivo Evaluation
Curr. Drug Deliv. 21, 1537 (2024); https://doi.org/10.2174/0115672018279370240103062944
/content/journals/cdd/10.2174/0115672018279370240103062944
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  • Article Type:     Research Article
Keyword(s): dual reservoir slow release; gel; Linagliptin; microparticle; spray drying method; transdermal drug delivery systems

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