A Study on the Formulation and Optimization of Nanostructured Lipid Carriers for Bempedoic Acid with Improved Biorelevant Intestinal Solubilization

References

[1] Laufs U, Banach M, Mancini GBJ, et al. Efficacy and safety of bempedoic acid in patients with hypercholesterolemia and statin intolerance. J. Am. Heart Assoc. 2019;8(7):e011662. https://doi.org/10.1161/JAHA.118.011662

[2] Goldberg AC, Leiter LA, Stroes ESG, et al. Effect of bempedoic acid vs placebo added to maximally tolerated statins on low-density lipoprotein cholesterol in patients at high risk for cardiovascular disease: The CLEAR Wisdom randomized clinical trial. JAMA. 2019;322(18):1780–1788. https://doi.org/10.1001/jama.2019.16585

[3] Pinkosky SL, Newton RS, Day EA, et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat. Commun. 2016;7:13457. https://doi.org/10.1038/ncomms13457

[4] Ray KK, Bays HE, Catapano AL, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N. Engl. J. Med. 2019;380(11):1022–1032. https://doi.org/10.1056/NEJMoa1803917

[5] Charman WN. Lipids, lipophilic drugs, and oral drug delivery: Some emerging concepts. J. Pharm. Sci. 2000;89(8):967–978. https://doi.org/10.1002/1520-6017(200008)89:8<967::AID-JPS1>3.0.CO;2-R

[6] Porter CJH, Charman WN. In vitro assessment of oral lipid based formulations. Adv. Drug Deliv. Rev. 2001;50:S127–S147. https://doi.org/10.1016/S0169-409X(01)00182-X

[7] Kossena GA, Charman WN, Boyd BJ, Porter CJH. Influence of the intermediate digestion phases of common formulation lipids on the absorption of a poorly water-soluble drug. J. Pharm. Sci. 2005;94(3):481–492. https://doi.org/10.1002/jps.20260

[8] Pouton CW. Formulation of poorly water-soluble drugs for oral administration: Physicochemical and physiological issues and the lipid formulation classification system. Eur. J. Pharm. Sci. 2006;29(3–4):278–287. https://doi.org/10.1016/j.ejps.2006.04.016

[9] Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv. Drug Deliv. Rev. 2002;54:S131–S155. https://doi.org/10.1016/S0169-409X(02)00118-7

[10] Elmowafy M, Al-Sanea MM. Nanostructured lipid carriers (NLCs) as drug delivery platform: Advances in formulation and delivery strategies. Saudi Pharm. J. 2021;29(9):999–1012. https://doi.org/10.1016/j.jsps.2021.07.015

[11] Larsen AT, Ogbonna A, Abu-Rmaileh R, Abrahamsson B, Østergaard J, Müllertz A. Use of in vitro lipolysis models for the evaluation of lipid-based formulations. J. Pharm. Sci. 2011;100(9):3478–3487. https://doi.org/10.1002/jps.22298

[12] Williams HD, Sassene P, Kleberg K, et al. Toward the establishment of standardized in vitro tests for lipid-based formulations, Part 1: In vitro digestion model and phase identification. J. Pharm. Sci. 2012;101(9):3360–3380. https://doi.org/10.1002/jps.23205

[13] Beloqui A, Solinís MÁ, Rodríguez-Gascón A, Almeida AJ, Préat V. Mechanism of transport of saquinavir-loaded nanostructured lipid carriers across the intestinal barrier. J. Control. Release. 2013;166(2):115–123. https://doi.org/10.1016/j.jconrel.2012.12.021

[14] Vithani K, Jannin V, Pouton CW, Boyd BJ. Colloidal aspects of dispersion and digestion of self-dispersing lipid-based formulations for poorly water-soluble drugs. Adv. Drug Deliv. Rev. 2019;142:16–34. https://doi.org/10.1016/j.addr.2019.01.008

@article{1725019,
      author = {S. Venkat Naveen, I. Nagaraju, Dr. G. S. Valluri, G. Vijaya Kumar},
      title = {A Study on the Formulation and Optimization of Nanostructured Lipid Carriers for Bempedoic Acid with Improved Biorelevant Intestinal Solubilization},
      journal = {Iconic Research And Engineering Journals},
      year = {2026},
      volume = {10},
      number = {5},
      pages = {2254-2260},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1725019.pdf},
      abstract = {Bempedoic acid is an ATP-citrate lyase inhibitor used to reduce low-density lipoprotein cholesterol; however, its poor aqueous solubility under acidic conditions and pH-dependent dissolution may limit gastrointestinal drug availability. This study aimed to develop and optimize an aqueous nanostructured lipid carrier (NLC) dispersion to improve bempedoic acid release and biorelevant intestinal solubilization. Pre-formulation screening evaluated drug solubility in solid and liquid lipids, lipid–aqueous partitioning, drug–excipient compatibility, and surfactant emulsification. Precirol® ATO 5 and Capryol® 90 were selected as the solid and liquid lipid components, respectively, at an 80:20 ratio; Tween® 80 and Poloxamer 188 were selected as the stabilizer system. NLCs were prepared by hot homogenization followed by probe ultrasonication. The optimized dispersion exhibited a particle size of 145.8 ± 4.9 nm, polydispersity index (PDI) of 0.21 ± 0.02, zeta potential of −24.7 ± 1.5 mV, entrapment efficiency of 86.3 ± 2.4%, drug loading of 4.6 ± 0.3%, and drug content of 98.9 ± 1.7%. In pH-shift release testing, cumulative release at 24 h was 79.3 ± 3.1% for NLCs compared with 28.7 ± 2.2% for plain drug suspension. Release data were best fitted by the Korsmeyer–Peppas model (R² = 0.989; n = 0.52). During pH-stat lipolysis, 67.9 ± 3.4% of the drug remained in the micellar/aqueous fraction for NLCs compared with 24.6 ± 2.8% for suspension. The dispersion maintained its quality more effectively at 4°C than at 25°C over 30 days, whereas accelerated storage produced particle growth and PDI increase. The findings demonstrate improved in vitro release and digestion-phase solubilization; in vivo pharmacokinetic confirmation remains necessary.},
      keywords = {Bempedoic acid, intestinal solubilization, lipid-based formulation, lipolysis, nanostructured lipid carriers},
      month = {November},
  }