5-fluorouracil; glycerol monostearate; stearic acid; compritol®; cholesterol.


Objective: The study's objective involved compatibility studies to investigate the possible interactions between 5-fluorouracil (5-FU) and four different lipids, and the most appropriate lipid was chosen. 

  Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier Transform Infrared spectroscopy (FT-IR) are used for the compatibility study between 5-FU and several excipients as cholesterol, compritol®, stearic acid, and glycerol monostearate (GMS).

Methods: The physical mixture between 5-FU and each lipid was made by mixing of a certain amount of drug with the same amount of lipid. Drug lipid blended mixtures were made by solvent evaporation casting method. 5-FU alone, physical mixture and blended mixture were measured using Differential scanning calorimetry (DSC) to investigate melting peak of drug and effect of each lipid on this melting point, X-ray diffraction (XRD) to observe the crystalline or amorphous state of drug and Fourier Transform Infrared (FT-IR) to determine any chemical interaction between drug and these lipids by observing any shift happened to characteristic peaks related to the drug.

Results: 5-FU Tm (280.04 °C) peak appeared in drug-lipid physical mixtures with minor changes in position while this peak disappeared in 5-FU-compritol® and 5-FU-cholesterol blended mixture indicating that the drug is molecular dispersed. XRD result showed that the crystalline structure of 5-FU was present in physical mixtures with four lipids while in the 5-FU-compritol® blended mixture, the crystalline state of the drug was disappeared confirming the DSC result.

    The FT-IR spectrum of the 5-FU-physical mixtures with four lipids showed that all characteristic peaks of the drug appeared with minor changes. In the case of 5-FU-blended mixtures with mentioned lipids, no chemical interaction occurred between the drug and mentioned lipids except in the drug-stearic acid blended mixture, the N-H peak at 3136.25cm-1 was disappeared due to amide ester formation.

Conclusion: The most appropriate lipids suitable for the preparation of 5-FU solid lipid nanoparticles were GMS and cholesterol.


Download data is not yet available.


Bakkialakshmi S, Chandrakala D. Thermodynamic studies on the interaction of 5-Fluorouracil with human serum albumin. Int J Pharm Pharm Sci. 2012;5:46-9.

Patel MN, Lakkadwala S, Majrad MS, Injeti ER, Gollmer SM, Shah ZA, et al. Characterization and evaluation of 5-fluorouracil-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification technique. Aaps Pharmscitech. 2014;15(6):1498-508.

Smith T, Affram K, Nottingham EL, Han B, Amissah F, Krishnan S, et al. Application of smart solid lipid nanoparticles to enhance the efficacy of 5-fluorouracil in the treatment of colorectal cancer. Scientific reports. 2020;10(1):1-14.

Wörmann B, Bokemeyer C, Burmeister T, Köhne C-H, Schwab M, Arnold D, et al. Dihydropyrimidine dehydrogenase testing prior to treatment with 5-fluorouracil, capecitabine, and Tegafur: A consensus paper. Oncology Research and Treatment. 2020;43(11):628-36.

Nasir B, Ranjha NM, Hanif M, Nasir S, Abbas G, Afzal S, et al. pharmacokinetic studies of 5-fluorouracil in rabbit plasma. Acta Poloniae Pharmaceutica. 2017;74(5):1573-8.

Entezar-Almahdi E, Mohammadi-Samani S, Tayebi L, Farjadian F. Recent advances in designing 5-fluorouracil delivery systems: a stepping stone in the safe treatment of colorectal cancer. International Journal of Nanomedicine. 2020;15:5445.

Shenoy VS, Gude RP, Murthy RSR. In vitro anticancer evaluation of 5-fluorouracil lipid nanoparticles using B16F10 melanoma cell lines. International Nano Letters. 2013;3(1):1-9.

Bayat P, Pakravan P, Salouti M, Dolatabadi JEN. Lysine Decorated Solid Lipid Nanoparticles of Epirubicin for Cancer Targeting and Therapy. Advanced Pharmaceutical Bulletin. 2021;11(1):96.

Yasmin B, Prathyusha R. Formulation and evaluation of dasatinib loaded solid lipid nanoparticles. Int J Pharm Pharm Sci. 2018;10:14-20.

Wu D, Huang C, Chang S, Chen T, Lee H. Bcl-2 stabilization by paxillin confers 5-fluorouracil resistance in colorectal cancer. Cell Death & Differentiation. 2015;22(5):779-89.

Moura EA, Correia LP, Pinto MF, Procópio JVV, de Souza FS, Macedo RO. Thermal characterization of the solid state and raw material fluconazole by thermal analysis and pyrolysis coupled to GC/MS. Journal of thermal analysis and calorimetry. 2010;100(1):289-93.

BH JG, Shankar S, Munisamy M, RS A, Sagar V. Development of ph-dependent chronomodulated delivery systems of 5-fluorouracil and oxaliplatin to treat colon cancer. Int J App Pharm. 2020;12(5):118-30.

Bannach G, Cervini P, Cavalheiro ÉTG, Ionashiro M. Using thermal and spectroscopic data to investigate the thermal behavior of epinephrine. Thermochimica acta. 2010;499(1-2):123-7.

Kalepu S, Manthina M, Padavala V. Oral lipid-based drug delivery systems–an overview. Acta Pharmaceutica Sinica B. 2013;3(6):361-72.

Avery MA, Jennings-White C, Chong WK. Simplified analogs of the antimalarial artemisinin: synthesis of 6, 9-desmethylartemisinin. The Journal of Organic Chemistry. 1989;54(8):1792-5.

Sonntag NO. Glycerolysis of Fats and methyl esters—status, review and critique. Journal of the American Oil Chemists Society. 1982;59(10):795A-802A.

Mohamed AI, Samir N, El-Seidi EA, Hathout RMH, Abdel G, Awad S. Effect of Certain Pharmaceutical Polymers on Lomefloxacin Activity against Helicobacter pylori.

Rojas-Oviedo I, Retchkiman-Corona B, Quirino-Barreda C, Cárdenas J, Schabes-Retchkiman P. Solubility enhancement of a poorly water soluble drug by forming solid dispersions using mechanochemical activation. Indian journal of pharmaceutical sciences. 2012;74(6):505.

Tiţa B, Fuliaş A, Bandur G, Marian E, Tiţa D. Compatibility study between ketoprofen and pharmaceutical excipients used in solid dosage forms. Journal of Pharmaceutical and Biomedical Analysis. 2011;56(2):221-7.

Slobozeanu AE, Bejan SE, Tudor IA, Mocioiu A-M, Motoc AM, Romero-Sanchez MD, et al. A review on differential scanning calorimetry as a tool for thermal assessment of nanostructured coatings. Manufacturing Review. 2021;8:1.

Aburahma MH, Badr-Eldin SM. Compritol 888 ATO: a multifunctional lipid excipient in drug delivery systems and nanopharmaceuticals. Expert opinion on drug delivery. 2014;11(12):1865-83.

Pignatello R, Ferro M, Puglisi G. Preparation of solid dispersions of nonsteroidal anti-inflammatory drugs with acrylic polymers and studies on mechanisms of drug-polymer interactions. AAPS PharmSciTech. 2002;3(2):35-45.

Olukman M, Şanlı O, Solak EK. Release of anticancer drug 5-Fluorouracil from different ionically crosslinked alginate beads. Journal of Biomaterials and Nanobiotechnology. 2012;3(04):469.

Mohammed AM, Osman SK, Saleh KI, Samy AM. In Vitro Release of 5-Fluorouracil and Methotrexate from Different Thermosensitive Chitosan Hydrogel Systems. AAPS PharmSciTech. 2020;21:1-11.

Moghimipour E, Handali S. Utilization of thin film method for preparation of celecoxib loaded liposomes. Advanced pharmaceutical bulletin. 2012;2(1):93.

Vyas PM, Vasant SR, Hajiyani RR, Joshi MJ, editors. Synthesis and Characterization of cholesterol nano particles by Using w/o Microemulsion Technique. AIP Conference Proceedings; 2010: American Institute of Physics.

Rostamkalaei SS, Akbari J, Saeedi M, Morteza-Semnani K, Nokhodchi A. Topical gel of Metformin solid lipid nanoparticles: A hopeful promise as a dermal delivery system. Colloids and Surfaces B: Biointerfaces. 2019;175:150-7.

Chiang TC, Hamdan S, Osman MS. Urea formaldehyde composites reinforced with Sago fibres analysis by FTIR, TGA, and DSC. Advances in Materials Science and Engineering. 2016;2016.

Hussain T, Saeed T, Mumtaz AM, Javaid Z, Abbas K, Awais A, et al. Effect of two hydrophobic polymers on the release of gliclazide from their matrix tablets. Acta poloniae pharmaceutica. 2013;70(4):749-57.

Fang G, Li H, Chen Z, Liu X. Preparation and characterization of stearic acid/expanded graphite composites as thermal energy storage materials. Energy. 2010;35(12):4622-6.

Kang J-H, Yoo K-H, Park H-Y, Hyun S-M, Han S-D, Kim D-W, et al. Preparation and In Vivo Evaluation of a Lidocaine Self-Nanoemulsifying Ointment with Glycerol Monostearate for Local Delivery. Pharmaceutics. 2021;13(9):1468.

Reddy YD, Dhachinamoorthi D. Formulation and in vitro evaluation of antineoplastic drug loaded nanoparticles as drug delivery system. African Journal of Pharmacy and Pharmacology. 2013;7(23):1592-604.

Fouladian P, Kohlhagen J, Arafat M, Afinjuomo F, Workman N, Abuhelwa AY, et al. Three-dimensional printed 5-fluorouracil eluting polyurethane stents for the treatment of oesophageal cancers. Biomaterials Science. 2020;8(23):6625-36.

Veerabrahma K. Development of olmesartan medoxomil lipid-based nanoparticles and nanosuspension: preparation, characterization and comparative pharmacokinetic evaluation. Artificial cells, nanomedicine, and biotechnology. 2017;46(1):126-37.

Jia L-J, Zhang D-R, Li Z-Y, Feng F-F, Wang Y-C, Dai W-T, et al. Preparation and characterization of silybin-loaded nanostructured lipid carriers. Drug delivery. 2010;17(1):11-8.

Yusefi M, Shameli K, Jahangirian H, Teow S-Y, Umakoshi H, Saleh B, et al. The Potential Anticancer Activity of 5-Fluorouracil Loaded in Cellulose Fibers Isolated from Rice Straw. International journal of nanomedicine. 2020;15:5417.

Vasuki G, Selvaraju R. Growth and thermal charachterization of choleaterol crystals. Int J Modn Res Revs. 2014;2(9):287-9.

Gupta U, Singh VK, Kumar V, Khajuria Y. Spectroscopic studies of cholesterol: fourier transform infra-red and vibrational frequency analysis. Materials Focus. 2014;3(3):211-7.

Cisse A, Peters J, Lazzara G, Chiappisi L. PyDSC: a simple tool to treat differential scanning calorimetry data. Journal of Thermal Analysis and Calorimetry. 2020:1-7.

Gardouh AR, Gad S, Ghonaim HM, Ghorab MM. Design and characterization of glyceryl monostearate solid lipid nanoparticles prepared by high shear homogenization. Journal of Pharmaceutical Research International. 2013:326-46.

Wang M, Yuan Y, Gao Y, Ma H-M, Xu H-T, Zhang X-N, et al. Preparation and characterization of 5-fluorouracil pH-sensitive niosome and its tumor-targeted evaluation: in vitro and in vivo. Drug development and industrial pharmacy. 2012;38(9):1134-41.

Jenning V, Thünemann AF, Gohla SH. Characterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids. International journal of pharmaceutics. 2000;199(2):167-77.

Souto E, Mehnert W, Müller R. Polymorphic behaviour of Compritol® 888 ATO as bulk lipid and as SLN and NLC. Journal of microencapsulation. 2006;23(4):417-33.

Nasr M, Ghorab MK, Abdelazem A. In vitro and in vivo evaluation of cubosomes containing 5-fluorouracil for liver targeting. Acta pharmaceutica sinica B. 2015;5(1):79-88.

Fouad EA, Yassin AEB, Alajami HN. Characterization of celecoxib-loaded solid lipid nanoparticles formulated with tristearin and softisan 100. Tropical Journal of Pharmaceutical Research. 2015;14(2):205-10.

Maher S, Santos A, Kumeria T, Kaur G, Lambert M, Forward P, et al. Multifunctional microspherical magnetic and pH responsive carriers for combination anticancer therapy engineered by droplet-based microfluidics. Journal of Materials Chemistry B. 2017;5(22):4097-109.

Arafat M, Fouladian P, Wignall A, Song Y, Parikh A, Albrecht H, et al. Development and In Vitro Evaluation of 5-Fluorouracil-Eluting Stents for the Treatment of Colorectal Cancer and Cancer-Related Obstruction. Pharmaceutics. 2021;13(1):17.

Andalib S, Varshosaz J, Hassanzadeh F, Sadeghi H. Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design. Advanced biomedical research. 2012;1.

Stulzer H, Rodrigues P, Cardoso T, Matos J, Silva M. Compatibility studies between captopril and pharmaceutical excipients used in tablets formulations. Journal of thermal analysis and calorimetry. 2008;91(1):323-8.

Rodríguez I, Gautam R, Tinoco AD. Using X-ray Diffraction Techniques for Biomimetic Drug Development, Formulation, and Polymorphic Characterization. Biomimetics. 2021;6(1):1.

Tummala S, Kumar MS, Prakash A. Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer. Saudi Pharmaceutical Journal. 2015;23(3):308-14.

Sekhar EC, Rao KK, Raju RR. Chitosan/guargum-g-acrylamide semi IPN microspheres for controlled release studies of 5-Fluorouracil. Journal of Applied Pharmaceutical Science. 2011;1(8):199.

E Eleraky N, M Omar M, A Mahmoud H, A Abou-Taleb H. Nanostructured lipid carriers to mediate brain delivery of temazepam: Design and in vivo study. Pharmaceutics. 2020;12(5):451.

Freire F, Aragão C, de Lima e Moura T, Raffin F. Compatibility study between chlorpropamide and excipients in their physical mixtures. Journal of thermal analysis and calorimetry. 2009;97(1):355-7.

Kelani KM, Rezk MR, Monir HH, ElSherbiny MS, Eid SM. FTIR combined with chemometric tools (fingerprinting spectroscopy) in comparison to HPLC: which strategy offers more opportunities as a green analytical chemistry technique for pharmaceutical analysis. Analytical Methods. 2020;12(48):5893-907.

Katharotiya K, Shinde G, Katharotiya D, Shelke S, Patel R, Kulkarni D, et al. Development, evaluation and biodistribution of stealth liposomes of 5-fluorouracil for effective treatment of breast cancer. Journal of Liposome Research. 2021:1-13.

Borderwala K, Rathod S, Yadav S, Vyas B, Shah P. Eudragit S-100 Surface Engineered Nanostructured Lipid Carriers for Colon Targeting of 5-Fluorouracil: Optimization and In Vitro and In Vivo Characterization. AAPS PharmSciTech. 2021;22(6):1-15.

Butler RN, O'Regan CB, Moynihan P. Reactions of fatty acids with amines. Part 2. Sequential thermal reactions of stearic (octadecanoic) acid with some 1, 2-and 1, 3-aminoalcohols and bis-amines. Journal of the Chemical Society, Perkin Transactions 1. 1978(4):373-7.

Raman S. Formulation and in-vitro charachterization of 5-fluorouracil and flavonoid dual lipid drug conjugates loaded self nanomulsifying drug delivery system for cancer targetting. IJPSR. 2019;10(7).

Miri B, Motakef-Kazemi N, Shojaosadati SA, Morsali A. Application of a nanoporous metal organic framework based on iron carboxylate as drug delivery system. Iranian journal of pharmaceutical research: IJPR. 2018;17(4):1164.

Kumar V, Kumar B, Deeba F, Bano S, Kulshreshtha A, Gopinath P, et al. Lipophilic 5-fluorouracil prodrug encapsulated xylan-stearic acid conjugates nanoparticles for colon cancer therapy. International journal of biological macromolecules. 2019;128:204-13.

Shenoya VS, Gude RP, RAMACHANDRA MRS. In vitro anticancer evaluation of 5-fluorouracil lipid nanoparticles using B16F10 melanoma cell Lines. 2012.

Nirbhavane P, Vemuri N, Kumar N, Khuller GK. Lipid nanocarrier-mediated drug delivery system to enhance the oral bioavailability of rifabutin. AAPS PharmSciTech. 2017;18(3):829-37.



How to Cite




Original Article(s)