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2000
Volume 3, Issue 1
  • ISSN: 2666-7312
  • E-ISSN: 2666-7339

Abstract

Background

Cardiac arrhythmia is a health concern, requiring effective medication for proper treatment. Diltiazem hydrochloride (DTZ.HCL), a class IV anti-arrhythmic calcium channel blocker, was used as a model drug due to its ability to block Ca++ channels in the SA and AV nodes, reducing calcium entry into cardiac cells and subsequently decreasing the force of contraction and oxygen consumption by the heart. Despite its good oral absorption, DTZ.HCL bioavailability is reduced to approximately 40% due to extensive first-pass metabolism. A nano-enabled drug delivery system has the advantage of incorporating both lipophilic and hydrophilic drugs with improved physical stability and enhanced bioavailability.

Objective

The objective of this study was to develop a solid-lipid formulation utilizing diltiazem hydrochloride and evaluate it for its bioavailability enhancement.

Methods

In the experimental study, SLNs were prepared using the microemulsion technique. A blend ratio (1:1) of lipid (stearic acid: compritol 888 ATO), span 80, PEG 200, and water was selected based on the microemulsion region obtained from the Triplot (4.1) ternary phase diagram. The hydrophilic drug diltiazem hydrochloride was incorporated into the lipid blend, and a preheated Smix was maintained at 80°C to obtain a transparent microemulsion, which then crystallized to form SLNs upon subsequent dispersion in cold water (1:25). Critical process parameters, including magnetic stirring speed, homogenizer speed, and probe sonication cycle, were optimized using Design Expert 10 software to achieve the desired particle size diameter, PDI, and entrapment efficiency.

Results

The results revealed that the particle size and PDI were significantly influenced by the span 80 and PEG 200. An increase in the concentration of the lipid blend resulted in large particle sizes. The optimized formulation showed a particle size of 415.4 ± 0.2 nm, PDI of 0.184 ± 0.01, and zeta potential of -24.19 ± 0.12 mV. These results were corroborated by DSC thermograms, which indicated reduced enthalpy associated with the reduced particle size of SLNs. Given that diltiazem hydrochloride is a hydrophilic drug with high water solubility, the entrapment efficiency was relatively 30.6% ± 0.45. release studies demonstrated an initial burst release, followed by a sustained release of 85% over 24 hours. The optimized SLNs followed the Higuchi matrix model, with a coefficient of correlation (R2) value of 0.9369.

Conclusion

Results concluded successful development of SLNs with improved bioavailability when compared by way of method with marketed preparations.

© 2024 Bentham Science Publishers
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2024-10-14
2025-10-30

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References

  1. JayeD.A. XiaoY. SiggD.C. Cardiac Electrophysiology Methods and Models.ChamSpringer2010415210.1007/978‑1‑4419‑6658‑2_2
     [Google Scholar]
  2. DurhamD. WorthleyL.I.G. Cardiac arrhythmias: Diagnosis and management. The tachycardias.Crit. Care Resusc.200241355310.1016/S1441‑2772(23)00717‑216573402
     [Google Scholar]
  3. BuckleyM.M.T. GrantS.M. GoaK.L. McTavishD. SorkinE.M. Diltiazem.Drugs199039575780610.2165/00003495‑199039050‑000092191851
     [Google Scholar]
  4. KendallM.J. OkopskiJ.V. Calcium antagonism--with special reference to diltiazem.J. Clin. Pharm. Ther.198611315917410.1111/j.1365‑2710.1986.tb00841.x3528227
     [Google Scholar]
  5. TripathiK.D. Essentials of medical pharmacology.Daryaganj New DelhiJaypeeDigital200810.5005/jp/books/10282
     [Google Scholar]
  6. MandawgadeS.D. PatravaleV.B. Development of SLNs from natural lipids: Application to topical delivery of tretinoin.Int. J. Pharm.20083631-213213810.1016/j.ijpharm.2008.06.02818657601
     [Google Scholar]
  7. MüllerR.H. RadtkeM. WissingS.A. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations.Adv. Drug Deliv. Rev.200254Suppl. 1S131S15510.1016/S0169‑409X(02)00118‑712460720
     [Google Scholar]
  8. HuoJ. ZhouS. New research on development of solid lipid nanoparticles.J. Med. Coll. PLA200722638539010.1016/S1000‑1948(08)60023‑4
     [Google Scholar]
  9. LimS.B. BanerjeeA. ÖnyükselH. Improvement of drug safety by the use of lipid-based nanocarriers.J. Control. Release20121631344510.1016/j.jconrel.2012.06.00222698939
     [Google Scholar]
  10. NaseriN. ValizadehH. Zakeri-MilaniP. Solid lipid nanoparticles and nanostructured lipid carriers: Structure, preparation and application.Adv. Pharm. Bull.20155330531310.15171/apb.2015.04326504751
     [Google Scholar]
  11. 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)00087‑410840199
     [Google Scholar]
  12. YadavN. KhatakS. Singh SaraU.V. Solid lipid nanoparticles- A review.Int J Appl Pharm.201352818
     [Google Scholar]
  13. AnurakL. ChansiriG. PeankitD. SomlakK. Griseofulvin solid lipid nanoparticles based on microemulsion technique.Adv. Mat. Res.2011197-198475010.4028/www.scientific.net/AMR.197‑198.47
     [Google Scholar]
  14. NegiJ.S. ChattopadhyayP. SharmaA.K. RamV. Development of solid lipid nanoparticles (SLNs) of lopinavir using hot self nano-emulsification (SNE) technique.Eur. J. Pharm. Sci.2013481-223123910.1016/j.ejps.2012.10.02223153618
     [Google Scholar]
  15. GhadiriM. FatemiS. VatanaraA. DoroudD. NajafabadiA.R. DarabiM. RahimiA.A. Loading hydrophilic drug in solid lipid media as nanoparticles: Statistical modeling of entrapment efficiency and particle size.Int. J. Pharm.20124241-212813710.1016/j.ijpharm.2011.12.03722227603
     [Google Scholar]
  16. PrabhakarK. AfzalS.M. SurenderG. KishanV. Tween 80 containing lipid nanoemulsions for delivery of indinavir to brain.Acta Pharm. Sin. B20133534535310.1016/j.apsb.2013.08.001
     [Google Scholar]
  17. DasS. ChaudhuryA. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery.AAPS PharmSciTech2011121627610.1208/s12249‑010‑9563‑021174180
     [Google Scholar]
  18. ShuklaS. PanditV. Trojan Microparticles : A Composite Nanoparticle Delivery System.Curr. Drug Ther.202419441342510.2174/1574885518666230726142855
     [Google Scholar]
  19. KaurI.P. BhandariR. A method to prepare solid lipid nanoparticles with improved entrapment efficiency of hydrophilic drugs.Curr. Nanosci.201392110
     [Google Scholar]
  20. KakkarV. KaurI.P. Preparation, characterization and scale-up of sesamol loaded solid lipid nanoparticles.Nanotechnol. Devel.201221810.4081/nd.2012.e8
     [Google Scholar]
  21. AburahmaM.H. Badr-EldinS.M. Compritol 888 ATO: A multifunctional lipid excipient in drug delivery systems and nanopharmaceuticals.Expert Opin. Drug Deliv.201411121865188310.1517/17425247.2014.93533525152197
     [Google Scholar]
  22. BhoopB.S. Quality by design (QbD) for holistic Pharma excellence and regulatory compliance.Pharm. Times20144682633
     [Google Scholar]
  23. SinghB. KapilR. NandiM. AhujaN. Developing oral drug delivery systems using formulation by design: Vital precepts, retrospect and prospects.Expert Opin. Drug Deliv.20118101341136010.1517/17425247.2011.60512021790511
     [Google Scholar]
  24. SinghB. KapilR. BandyopadhyayS. AhujaN. Drug delivery optimization using experimental designs.2023
     [Google Scholar]
  25. SinghB. DahiyaM. SaharanV. AhujaN. Optimizing drug delivery systems using systematic “design of experiments.” Part II: Retrospect and prospects.Crit. Rev. Ther. Drug Carrier Syst.200522321529410.1615/CritRevTherDrugCarrierSyst.v22.i3.1015896189
     [Google Scholar]
  26. SinghS. DobhalA.K. JainA. PanditJ.K. ChakrabortyS. Formulation and evaluation of solid lipid nanoparticles of a water soluble drug: Zidovudine.Chem. Pharm. Bull. (Tokyo)201058565065510.1248/cpb.58.65020460791
     [Google Scholar]
  27. PoojaD. TunkiL. KulhariH. ReddyB.B. SistlaR. Optimization of solid lipid nanoparticles prepared by a single emulsification-solvent evaporation method.Data Brief201566151926759823
     [Google Scholar]
  28. SiewertM. DressmanJ. BrownC.K. ShahV.P. AiacheJ-M. AoyagiN. BashawD. BrownC. BrownW. BurgessD. CrisonJ. DeLucaP. DjerkiR. DressmanJ. FosterT. GjellanK. GrayV. HussainA. IngallineraT. KlanckeJ. KraemerJ. KristensenH. KumiK. LeunerC. LimbergJ. LoosP. MargulisL. MarroumP. MoellerH. MuellerB. Mueller-ZsigmondyM. OkafoN. OuderkirkL. ParsiS. QureshiS. RobinsonJ. ShahV. SiewertM. UppoorR. WilliamsR. FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms.AAPS PharmSciTech200341435210.1208/pt04010712916916
     [Google Scholar]
  29. VenkateswarluV. ManjunathK. Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles.J. Control. Release200495362763810.1016/j.jconrel.2004.01.00515023472
     [Google Scholar]
  30. SangsenY. LikhitwitayawuidK. SritularakB. WiwattanawongsaK. WiwattanapatapeeR. Novel solid lipid nanoparticles for oral delivery of oxyresveratrol: Effect of the formulation parameters on the physicochemical properties and in vitro release.Int. J. Pharm.20137877884
     [Google Scholar]
  31. NappinnaiM. KishoreV.S. Formulation and evaluation of microspheres of diltiazem hydrochloride.Indian J. Pharm. Sci.200769451151510.4103/0250‑474X.36935
     [Google Scholar]
  32. AkifuddinS. K. AbbasZ. Preparation, characterization and in-vitro evaluation of microcapsules for controlled release of diltiazem hydrochloride by ionotropic gelation technique.J. Appl. Pharm. Sci.2013304035042
     [Google Scholar]
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Formulation, Optimization, and Evaluation of Solid-lipid Formulation for Bioavailability Enhancement Utilizing Diltiazem Hydrochloride
Curr. Appl. Mat. 3, E26667312325351 (2024); https://doi.org/10.2174/0126667312325351241009063848
/content/journals/cam/10.2174/0126667312325351241009063848
/content/journals/cam/10.2174/0126667312325351241009063848
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  • Article Type:     Review Article
Keyword(s): Bioavailability; entrapment efficiency; microemulsion; pseudoternary phase diagram; solid lipid nanoparticles

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