Applicability of QbD-assisted Analytical Method for Simultaneous Detection of Tetrahydrocurcumin and Folic Acid in Developed Nanostructured Lipid Carriers

Page: [533 - 548] Pages: 16

  • * (Excluding Mailing and Handling)

Abstract

Aims: Applicability of QbD-assisted analytical method for simultaneous detection of tetrahydrocurcumin and folic acid in developed nanostructured lipid carriers.

Background: Diabetic foot ulcer (DFU) is a multifactorial disorder that involves chronic inflammation, oxidative stress and neuropathy. Current treatment therapies involving the use of growth factors and skin substitutes being costly, are out of reach for the majority of patients. The present research explored the usefulness of a combination of tetrahydrocurcumin and folic acid-loaded nanostructured lipidic carriers in DFU.

Objectives: To develop and validate a QbD-assisted method for simultaneous analysis of tetrahydrocurcumin (THC) and folic acid (FA). Applicability of the above method to determine total drug content (TDC) and entrapment efficiency (EE) of nanostructured lipid carriers (NLCs) loaded with THC and FA.

Methods: A high-performance liquid chromatographic (HPLC) method was developed, optimized and validated using Box-Behnken design for improved method performance. Chromatographic separation was conducted on a Supelco 250 x 4.6 mm (5 μm) column with optimized mobile phase composition containing tetrahydrofuran: citric acid buffer pH 3.5 (50:50) at a flow rate of 0.4 mL.min-1 and diode array detection between 210 and 360 nm.

Results: The method developed in a concentration range of 1 to 100 μg.mL-1 was found to be linear (R2 0.999, p≤0.001), accurate (99.10-101.70%) and precise with high recovery values in intra and inter-day results. The system adaptability and robustness evaluation revealed that the percent recovery ranged from 96.90 to 102.80%, and the percent relative standard deviation (%RSD) values were less than 2%. Moreover, the method was further applied for the determination of TDC (86±6% and 96±8%) and drug EE (81±21% and 73±13%) for THC and FA, respectively.

Conclusion: The investigation indicated the applicability of the developed and validated method for the estimation of THC and FA in the developed nanostructured lipidic carriers.

[1]
McDermott, K.; Fang, M.; Boulton, A.J.M.; Selvin, E.; Hicks, C.W. Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers. Diabetes Care, 2023, 46(1), 209-221.
[http://dx.doi.org/10.2337/dci22-0043] [PMID: 36548709]
[2]
Edmonds, M.; Manu, C.; Vas, P. The current burden of diabetic foot disease. J. Clin. Orthop. Trauma, 2021, 17, 88-93.
[http://dx.doi.org/10.1016/j.jcot.2021.01.017] [PMID: 33680841]
[3]
Oliver, T.I.; Mutluoglu, M. Diabetic Foot Ulcer. In: StatPearls; StatPearls Publishing: Treasure Island (FL), 2024.
[4]
Everett, E.; Mathioudakis, N. Update on management of diabetic foot ulcers. Ann. N. Y. Acad. Sci., 2018, 1411(1), 153-165.
[http://dx.doi.org/10.1111/nyas.13569] [PMID: 29377202]
[5]
Kakkar, V.; Kumari, P.; Narula, P.; Yaseen, M. Diabetic foot osteomyelitis: Control and therapy through nanotechnology. Nanotechnology in skin, soft tissue. Bone Infections., 2020, 1(1), 245-267.
[6]
Trivedi, M.K.; Gangwar, M.; Mondal, S.C.; Jana, S. Protective effects of tetrahydrocurcumin (THC) on fibroblast and melanoma cell lines in vitro: It’s implication for wound healing. J. Food Sci. Technol., 2017, 54(5), 1137-1145.
[http://dx.doi.org/10.1007/s13197-017-2525-8] [PMID: 28416863]
[7]
Aggarwal, B.; Deb, L.; Prasad, S. Curcumin differs from tetrahydrocurcumin for molecular targets, signaling pathways and cellular responses. Molecules, 2014, 20(1), 185-205.
[http://dx.doi.org/10.3390/molecules20010185] [PMID: 25547723]
[8]
Bhaskar Rao, A.; Prasad, E.; Deepthi, S.S.; Haritha, V.; Ramakrishna, S.; Madhusudan, K. Wound healing: A new perspective on glucosylated tetrahydrocurcumin. Drug Des Devel, 2015, 3579-3588.
[http://dx.doi.org/10.2147/DDDT.S85041]
[9]
Boykin, J.V., Jr; Hoke, G.D.; Driscoll, C.R.; Dharmaraj, B.S. High‐dose folic acid and its effect on early stage diabetic foot ulcer wound healing. Wound Repair Regen., 2020, 28(4), 517-525.
[http://dx.doi.org/10.1111/wrr.12804] [PMID: 32141182]
[10]
Yilmaz, M.; Aktug, H.; Oltulu, F.; Erbas, O. Neuroprotective effects of folic acid on experimental diabetic peripheral neuropathy. Toxicol. Ind. Health, 2016, 32(5), 832-840.
[http://dx.doi.org/10.1177/0748233713511513] [PMID: 24311627]
[11]
Garcia-Orue, I.; Pedraz, J.L.; Hernandez, R.M.; Igartua, M. Nanotechnology-based delivery systems to release growth factors and other endogenous molecules for chronic wound healing. J. Drug Deliv. Sci. Technol., 2017, 42, 2-17.
[http://dx.doi.org/10.1016/j.jddst.2017.03.002]
[12]
Imran, M.; Iqubal, M.K.; Imtiyaz, K.; Saleem, S.; Mittal, S.; Rizvi, M.M.A.; Ali, J.; Baboota, S. Topical nanostructured lipid carrier gel of quercetin and resveratrol: Formulation, optimization, in vitro and ex vivo study for the treatment of skin cancer. Int. J. Pharm., 2020, 587, 119705.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119705] [PMID: 32738456]
[13]
Wang, Y.J.; Pan, M.H.; Cheng, A.L.; Lin, L.I.; Ho, Y.S.; Hsieh, C.Y.; Lin, J.K. Stability of curcumin in buffer solutions and characterization of its degradation products. J. Pharm. Biomed. Anal., 1997, 15(12), 1867-1876.
[http://dx.doi.org/10.1016/S0731-7085(96)02024-9] [PMID: 9278892]
[14]
Amidžić, R.; Brborić, J.; Čudina, O.; Vladimirov, S. RP-HPLC determination of vitamins, folic acid and B12 in multivitamin tablets. J. Serb. Chem. Soc., 2005, 70(10), 1229-1235.
[http://dx.doi.org/10.2298/JSC0510229A]
[15]
Savitha, K.; Ravichandran, S. Technology. Method development and validation for simulataneous estimation of biotin and folic acid in bulk and tablet dosage form by RP-HPLC. Res. J. Pharm., 2020, 13(11), 5289-5292.
[16]
Zheng, X.H.; Jiang, L.Y.; Zhao, L.T.; Zhang, Q.Y.; Ding, L. Simultaneous quantitation of folic acid and 5-methyltetrahydrofolic acid in human plasma by HPLC–MS/MS and its application to a pharmacokinetic study. J. Pharm. Anal., 2015, 5(4), 269-275.
[http://dx.doi.org/10.1016/j.jpha.2015.05.004] [PMID: 29403940]
[17]
Awasthi, A.; Kumar, A.; Kumar, R.; Vishwas, S.; Khursheed, R.; Kaur, J.; Corrie, L.; Kumar, B.; Gulati, M.; Kumar, D.; Kaushik, M.; Gupta, G.; Prasher, P.; Chellappan, D.K.; Kumar, A.P.; Dua, K.; Singh, S.K. RP-HPLC method development and validation for simultaneous estimation of mesalamine and curcumin in bulk form as well as nanostructured lipid carriers. S. Afr. J. Bot., 2022, 151, 529-537.
[http://dx.doi.org/10.1016/j.sajb.2022.05.044]
[18]
Jastrebova, J.; Witthöft, C.; Grahn, A.; Svensson, U.; Jägerstad, M. HPLC determination of folates in raw and processed beetroots. Food Chem., 2003, 80(4), 579-588.
[http://dx.doi.org/10.1016/S0308-8146(02)00506-X]
[19]
Doherty, R.F.; Beecher, G.R. A method for the analysis of natural and synthetic folate in foods. J. Agric. Food Chem., 2003, 51(2), 354-361.
[http://dx.doi.org/10.1021/jf0259056] [PMID: 12517095]
[20]
Cao, Y.; Xu, R.X.; Liu, Z. A high-throughput quantification method of curcuminoids and curcumin metabolites in human plasma via high-performance liquid chromatography/tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2014, 949-950, 70-78.
[http://dx.doi.org/10.1016/j.jchromb.2013.12.039] [PMID: 24480327]
[21]
Polak, B.; Pajurek, E. Separation of some vitamins in reversed-phase thin-layer chromatography and pressurized planar electrochromatography with eluent containing surfactant. Sci. Rep., 2021, 11(1), 21851.
[http://dx.doi.org/10.1038/s41598-021-01323-1] [PMID: 34750458]
[22]
Jiao, Z.; Wang, X.; Yin, Y.; Xia, J.; Mei, Y. Preparation and evaluation of a chitosan-coated antioxidant liposome containing vitamin C and folic acid. J. Microencapsul., 2018, 35(3), 272-280.
[http://dx.doi.org/10.1080/02652048.2018.1467509] [PMID: 29671362]
[23]
Yadav, N.K.; Raghuvanshi, A.; Sharma, G.; Beg, S.; Katare, O.P.; Nanda, S. QbD-based development and validation of a stability-indicating HPLC method for estimating ketoprofen in bulk drug and proniosomal vesicular system. J. Chromatogr. Sci., 2016, 54(3), 377-389.
[PMID: 26514627]
[24]
Nagaraja, P.; Vasantha, R.A.; Yathirajan, H.S. Spectrophotometric determination of folic acid in pharmaceutical preparations by coupling reactions with iminodibenzyl or 3-aminophenol or sodium molybdate–pyrocatechol. Anal. Biochem., 2002, 307(2), 316-321.
[http://dx.doi.org/10.1016/S0003-2697(02)00038-6] [PMID: 12202249]
[25]
De Brouwer, V.; Storozhenko, S.; Stove, C.P.; Van Daele, J.; Van Der Straeten, D.; Lambert, W.E. Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) for the sensitive determination of folates in rice. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2010, 878(3-4), 509-513.
[http://dx.doi.org/10.1016/j.jchromb.2009.12.032] [PMID: 20061193]
[26]
Nair, A.; Jacob, S.; Al-Dhubiab, B.; Attimarad, M.; Harsha, S. Basic considerations in the dermatokinetics of topical formulations. Braz. J. Pharm. Sci., 2013, 49(3), 423-434.
[http://dx.doi.org/10.1590/S1984-82502013000300004]
[27]
Jayaprakasha, G.K.; Jagan Mohan Rao, L.; Sakariah, K.K. Improved HPLC method for the determination of curcumin, demethoxycurcumin, and bisdemethoxycurcumin. J. Agric. Food Chem., 2002, 50(13), 3668-3672.
[http://dx.doi.org/10.1021/jf025506a] [PMID: 12059141]
[28]
Liu, A.; Lou, H.; Zhao, L.; Fan, P. Validated LC/MS/MS assay for curcumin and tetrahydrocurcumin in rat plasma and application to pharmacokinetic study of phospholipid complex of curcumin. J. Pharm. Biomed. Anal., 2006, 40(3), 720-727.
[http://dx.doi.org/10.1016/j.jpba.2005.09.032] [PMID: 16316738]
[29]
Tan, A.; Wu, Y.; Wong, M.; Licollari, A.; Bolger, G.; Fanaras, J.C.; Shopp, G.; Helson, L. Use of basic mobile phase to improve chromatography and boost sensitivity for quantifying tetrahydrocurcumin in human plasma by LC–MS/MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2016, 1028, 86-93.
[http://dx.doi.org/10.1016/j.jchromb.2016.06.010] [PMID: 27327398]
[30]
ICH, Validation of analytical procedures: Text and methodology. International conference on harmonization, , Geneva, 2005.
[31]
Guideline, I.H. Analytical procedure development Q14; International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use: Geneva, Switzerland, 2022.
[32]
Beg, S.; Panda, S.S.; Singh, K.K. Chemometrics-assisted development of a validated LC method for simultaneous estimation of temozolomide and γ-linolenic acid: Greenness assessment and application to lipidic nanoparticles. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2022, 1200, 123261.
[http://dx.doi.org/10.1016/j.jchromb.2022.123261] [PMID: 35533423]
[33]
Zwain, T.; Alder, J.E.; Sabagh, B.; Shaw, A.; Burrow, A.J.; Singh, K.K. Tailoring functional nanostructured lipid carriers for glioblastoma treatment with enhanced permeability through in vitro 3D BBB/BBTB models. Mater. Sci. Eng. C, 2021, 121, 111774.
[http://dx.doi.org/10.1016/j.msec.2020.111774] [PMID: 33579439]
[34]
Bastogne, T.; Caputo, F.; Prina-Mello, A.; Borgos, S.; Barberi-Heyob, M.; Analysis, B. A state of the art in analytical quality-by-design and perspectives in characterization of nano-enabled medicinal products. J. Pharm. Biomed. Anal., 2022, 219, 114911.
[http://dx.doi.org/10.1016/j.jpba.2022.114911] [PMID: 35779356]
[35]
Bhutani, H.; Kurmi, M.; Singh, S.; Beg, S.; Singh, B. Quality by design (QbD) in analytical sciences: An overview. Qual. Assur., 2004, 3, 39-45.
[36]
Reddy Saddala, M.P.; Konduru, N.; Gundla, R.; Kowtharapu, L.P. Development and validation of novel RP‐HPLC method for midostaurin determination using analytical quality by design approach from regulatory perspective and determination of major degradation compounds of midostaurin using LC–MS. Biomed. Chromatogr., 2022, 36(12), e5486.
[http://dx.doi.org/10.1002/bmc.5486] [PMID: 36001450]
[37]
Jain, A.; Beg, S.; Saini, S.; Sharma, T.; Katare, O.P.; Singh, B. Application of chemometric approach for QbD-Enabled development and validation of an RP-HPLC method for estimation of methotrexate. J. Liq. Chromatogr. Relat. Technol., 2019, 42(15-16), 502-512.
[http://dx.doi.org/10.1080/10826076.2019.1626742]
[38]
Kaur, R.; Saini, S.; Sharma, T.; Katare, O.P.; Kaushik, A.; Singh, B. Implementation of analytical quality-by-design for developing a robust HPLC method for quantitative estimation of voriconazole: Application in drug formulations. Anal. Chem. Lett., 2021, 11(2), 168-186.
[http://dx.doi.org/10.1080/22297928.2021.1888793]
[39]
Dispas, A.; Avohou, H.T.; Lebrun, P.; Hubert, P.; Hubert, C. ‘Quality by Design’ approach for the analysis of impurities in pharmaceutical drug products and drug substances. Trends Analyt. Chem., 2018, 101, 24-33.
[http://dx.doi.org/10.1016/j.trac.2017.10.028]
[40]
Saini, S.; Sharma, T.; Patel, A.; Kaur, R.; Tripathi, S.K.; Katare, O.P.; Singh, B. QbD-steered development and validation of an RP-HPLC method for quantification of ferulic acid: Rational application of chemometric tools. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2020, 1155, 122300.
[http://dx.doi.org/10.1016/j.jchromb.2020.122300] [PMID: 32771967]
[41]
Singh, B.; Pahuja, S.; Kapil, R.; Ahuja, N. Formulation development of oral controlled release tablets of hydralazine: Optimization of drug release and bioadhesive characteristics. Acta Pharm., 2009, 59(1), 1-13.
[http://dx.doi.org/10.2478/v10007-009-0005-z] [PMID: 19304554]
[42]
Soliman, N.M.; Shakeel, F.; Haq, N.; Alanazi, F.K.; Alshehri, S.; Bayomi, M.; Alenazi, A.S.M.; Alsarra, I.A. Development and optimization of ciprofloxacin HCl-loaded chitosan nanoparticles using box–behnken experimental design. Molecules, 2022, 27(14), 4468.
[http://dx.doi.org/10.3390/molecules27144468] [PMID: 35889340]
[43]
Pant, A.; Sharma, G.; Saini, S.; Jain, A.; Barnwal, R.P.; Singh, G.; Singh, B. Quality by design‐steered development and validation of analytical and bioanalytical methods for raloxifene: Application of Monte Carlo simulations and variance inflation factor. Biomed. Chromatogr., 2023, 37(8), e5641.
[http://dx.doi.org/10.1002/bmc.5641] [PMID: 37041119]
[44]
Chaudhari, V.S.; Borkar, R.M.; Murty, U.S.; Banerjee, S. Analytical method development and validation of reverse-phase high-performance liquid chromatography (RP-HPLC) method for simultaneous quantifications of quercetin and piperine in dual-drug loaded nanostructured lipid carriers. J. Pharm. Biomed. Anal., 2020, 186, 113325.
[http://dx.doi.org/10.1016/j.jpba.2020.113325] [PMID: 32380356]
[45]
Liu, D.; Li, J.; Pan, H.; He, F.; Liu, Z.; Wu, Q.; Bai, C.; Yu, S.; Yang, X. Potential advantages of a novel chitosan-N-acetylcysteine surface modified nanostructured lipid carrier on the performance of ophthalmic delivery of curcumin. Sci. Rep., 2016, 6(1), 28796.
[http://dx.doi.org/10.1038/srep28796] [PMID: 27350323]
[46]
Janagam, D.R.; Wu, L.; Lowe, T.L. Nanoparticles for drug delivery to the anterior segment of the eye. Adv. Drug Deliv. Rev., 2017, 122, 31-64.
[http://dx.doi.org/10.1016/j.addr.2017.04.001] [PMID: 28392306]
[47]
Sandhu, P.S.; Beg, S.; Katare, O.P.; Singh, B. QbD-driven development and validation of a HPLC method for estimation of tamoxifen citrate with improved performance. J. Chromatogr. Sci., 2016, 54(8), 1373-1384.
[http://dx.doi.org/10.1093/chromsci/bmw090] [PMID: 27226463]
[48]
Alvarez-Segura, T.; Subirats, X.; Rosés, M. Retention-pH profiles of acids and bases in hydrophilic interaction liquid chromatography. Anal. Chim. Acta, 2019, 1050, 176-184.
[http://dx.doi.org/10.1016/j.aca.2018.11.021] [PMID: 30661587]
[49]
Zhang, Z.; Xia, M.; Huang, P.; Di, B.; Su, M. Preparation and evaluation of a bacitracin-bonded silica stationary phase for hydrophilic interaction liquid chromatography. Microchem. J., 2021, 170, 106661.
[http://dx.doi.org/10.1016/j.microc.2021.106661]
[50]
Huda, N.H.; Gauri, B.; Benson, H.A.; Chen, Y. A stability indicating HPLC assay method for analysis of rivastigmine hydrogen tartrate in dual-ligand nanoparticle formulation matrices and cell transport medium. J. Anal. Methods Chem., 2018, 2018, 1841937.
[http://dx.doi.org/10.1155/2018/1841937]
[51]
Hinge, N.S.; Pandey, M.M. Sensitive RP-HPLC method of rivastigmine for applicative quantification of nanostructured lipid carriers. Microchem. J., 2023, 188, 108341.
[http://dx.doi.org/10.1016/j.microc.2022.108341]
[52]
Narula, P.; Saini, K.; Saini, M.; Singla, D.; Chauhan, A.S.; Kakkar, V. Assay and dermatokinetics of tetrahydrocurcumin lipidic nanostructures using reverse phase-high performance liquid chromatography. Pharm. Nanotechnol., 2021, 9(2), 130-140.
[http://dx.doi.org/10.2174/2211738509999210128203251] [PMID: 33511962]
[53]
Kawano, S.; Inohana, Y.; Hashi, Y.; Lin, J.M. Analysis of keto-enol tautomers of curcumin by liquid chromatography/mass spectrometry. Chin. Chem. Lett., 2013, 24(8), 685-687.
[http://dx.doi.org/10.1016/j.cclet.2013.05.006]
[54]
Matwijczuk, A.; Karcz, D.; Walkowiak, R.; Furso, J.; Gładyszewska, B.; Wybraniec, S.; Niewiadomy, A.; Karwasz, G.P.; Gagoś, M. Effect of solvent polarizability on the keto/enol equilibrium of selected bioactive molecules from the 1, 3, 4-thiadiazole group with a 2, 4-hydroxyphenyl function. J. Phys. Chem. A, 2017, 121(7), 1402-1411.
[http://dx.doi.org/10.1021/acs.jpca.6b08707] [PMID: 28132511]
[55]
Yanagisawa, D.; Shirai, N.; Amatsubo, T.; Taguchi, H.; Hirao, K.; Urushitani, M.; Morikawa, S.; Inubushi, T.; Kato, M.; Kato, F.; Morino, K.; Kimura, H.; Nakano, I.; Yoshida, C.; Okada, T.; Sano, M.; Wada, Y.; Wada, K.; Yamamoto, A.; Tooyama, I. Relationship between the tautomeric structures of curcumin derivatives and their Aβ-binding activities in the context of therapies for Alzheimer’s disease. Biomaterials, 2010, 31(14), 4179-4185.
[http://dx.doi.org/10.1016/j.biomaterials.2010.01.142] [PMID: 20181392]
[56]
Sathishbabu, P.; Hani, U.; Shakeela, C.; Hemanth Vikram, P.R.; Ghazwani, M.; Osmani, R.A.M.; Gurupadayya, B.M.; Gowda, D.V. A novel RP-HPLC method development and validation for simultaneous quantification of gefitinib and resveratrol in polymeric hybrid lipid nanoparticles and glioma cells. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2022, 1212, 123483.
[http://dx.doi.org/10.1016/j.jchromb.2022.123483] [PMID: 36279777]
[57]
Kumar, M.; Sharma, G.; Singla, D.; Singh, S.; Sahwney, S.; Chauhan, A.S.; Singh, G.; Kaur, I.P. Development of a validated UPLC method for simultaneous estimation of both free and entrapped (in solid lipid nanoparticles) all-trans retinoic acid and cholecalciferol (vitamin D3) and its pharmacokinetic applicability in rats. J. Pharm. Biomed. Anal., 2014, 91, 73-80.
[http://dx.doi.org/10.1016/j.jpba.2013.12.011] [PMID: 24440824]
[58]
Kaur, R.; Saini, S.; Patel, A.; Sharma, T.; Kaur, R.; Katare, O.P.; Singh, B. Developing a validated HPLC method for quantification of ceftazidime employing analytical quality by design and Monte Carlo simulations. J. AOAC Int., 2021, 104(3), 620-632.
[http://dx.doi.org/10.1093/jaoacint/qsab014] [PMID: 33528003]