5-Aminosalicylic acid (5-ASA), the active moiety of sulphasalazine, is the most commonly used drug for treating patients with inflammatory bowel disease (IBD). Its bioavailability is low, i.e. 20–30% upon oral administration and 10–35% by rectal administration. As the extent of 5-ASA absorption is very much dependent on the time-length, the drug is retained in the colon, a way to increase drug retention is the use of orally administered sustained released formulations. Solid lipid microparticles (SLM) are a viable option for site-specific targeted delivery in compressed tablets produced by direct compaction. In this study, we describe the development and characterization of 5-ASA-loaded SLM for sustained release. The solubility of 5-ASA in different types of solid lipids (e.g. cetyl palmitate, cetyl alcohol, and cetearyl alcohol) was evaluated to select the best lipid as the inert matrix-forming agent to control the release of the drug. SLM dispersions were prepared using the hot emulsification method employing the selected solid lipid, lecithin (Lipoid®) as surfactant, dimethyl sulphoxide, and acetone stabilized with Arlacel®. The characterization was performed by differential scanning calorimetry, thermogravimetric analysis, wide-angle x-ray diffraction, Fourier transform infrared spectroscopy measurements, optical microscopy, and scanning electron microscopy. Results show that the best lipid for dissolving the 5-ASA was cetyl palmitate and that the melting process did not affect the chemical stability of the materials. The thermal analysis suggests that 5-ASA was successfully encapsulated with the microparticles, of spherical shape and uniform size distribution.
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Scalia S, Young PM, Traini D. Solid lipid microparticles as an approach to drug delivery. Expert Opin Drug Deliv. 2015;12(4):583–99.
Campos JR, Fernandes AR, Sousa R, Fangueiro JF, Boonme P, Garcia ML, et al. Optimization of nimesulide-loaded solid lipid nanoparticles (SLN) by factorial design, release profile and cytotoxicity in human Colon adenocarcinoma cell line. Pharm Dev Technol. 2019;24(5):616–22. https://doi.org/10.1080/10837450.2018.1549075.
Souto EB, Doktorovova S, Campos JR, Martins-Lopes P, Silva AM. Surface-tailored anti-HER2/neu-solid lipid nanoparticles for site-specific targeting MCF-7 and BT-474 breast cancer cells. Eur J Pharm Sci. 2019;128:27–35. https://doi.org/10.1016/j.ejps.2018.11.022.
Cho CH, Min JH, Hwang KM, Park ES. Development of sustained-release microparticles containing tamsulosin HCl for orally disintegrating tablet using melt-adsorption method. Drug Deliv Transl Res. 2018;8(3):552–64. https://doi.org/10.1007/s13346-018-0477-9.
Campos E, Branquinho J, Carreira AS, Carvalho A, Coimbra P, Ferreira P, et al. Designing polymeric microparticles for biomedical and industrial applications. Eur Polym J. 2013;49(8):2005–21.
Gomes GVL, Borrin TR, Cardoso LO, Souto E, Pinho SC. Characterization and shelf life of β-carotene loaded solid lipid microparticles produced with stearic acid and sunflower oil. Braz Arch Biol Technol. 2013;56(4):663–71. https://doi.org/10.1590/s1516-89132013000400017.
Doktorovova S, Kovacevic AB, Garcia ML, Souto EB. Preclinical safety of solid lipid nanoparticles and nanostructured lipid carriers: current evidence from in vitro and in vivo evaluation. Eur J Pharm Biopharm. 2016;108:235–52. https://doi.org/10.1016/j.ejpb.2016.08.001.
Doktorovova S, Souto EB, Silva AM. Nanotoxicology applied to solid lipid nanoparticles and nanostructured lipid carriers—a systematic review of in vitro data. Eur J Pharm Biopharm. 2014;87(1):1–18. https://doi.org/10.1016/j.ejpb.2014.02.005.
Mehnert W, Mäder K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2001;47(2):165–96.
Desreumaux P, Ghosh S. mode of action and delivery of 5-aminosalicylic acid—new evidence. Aliment Pharmacol Ther. 2006;24(s1):2–9.
Trendafilova I, Szegedi Á, Yoncheva K, Shestakova P, Mihály J, Ristić A, et al. A pH dependent delivery of mesalazine from polymer coated and drug-loaded SBA-16 systems. Eur J Pharm Sci. 2016;81:75–81.
Severino P, Pinho SC, Souto EB, Santana MH. Polymorphism, crystallinity and hydrophilic–lipophilic balance of stearic acid and stearic acid–capric/caprylic triglyceride matrices for production of stable nanoparticles. Colloids Surf B. 2011;86(1):125–30.
Severino P, Pinho SC, Souto EB, Santana MH. Crystallinity of Dynasan® 114 and Dynasan® 118 matrices for the production of stable Miglyol®-loaded nanoparticles. J Therm Anal Calorim. 2011;108(1):101–8.
Souto EB, Severino P, Santana MHA, Pinho SC. Solid lipid nanoparticles: classical methods of lab production. Quim Nova. 2011;34(10):1762–9.
Severino P, de Oliveira GGG, Ferraz HG, Souto EB, Santana MHA. Preparation of gastro-resistant pellets containing chitosan microspheres for improvement of oral didanosine bioavailability. J Pharm Anal. 2012;2(3):188–92. https://doi.org/10.1016/j.jpha.2012.02.005.
Jenning V, Thünemann AF, Gohla SH. Characterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids. Int J Pharm. 2000;199(2):167–77.
Ali F, Nandi U, Trivedi M, Prakash A, Dahiya M, Sahu PL, et al. Quantitative characterization and pharmaceutical compatibility between teneligliptin and widely used excipients by using thermal and liquid chromatography tandem mass spectrometry techniques. J Therm Anal Calorim. 2018;132(1):385–96. https://doi.org/10.1007/s10973-018-6962-z.
Nassar MY, El-Shahat M, Khalile S, El-Desawy M, Mohamed EA. Structure investigation of mesalazine drug using thermal analyses, mass spectrometry, DFT calculations, and NBO analysis. J Therm Anal Calorim. 2014;117(1):463–71.
Dantas IL, Bastos KTS, Machado M, Galvão JG, Lima AD, Gonsalves JKMC, et al. Influence of stearic acid and beeswax as solid lipid matrix of lipid nanoparticles containing tacrolimus. J Therm Anal Calorim. 2018;132(3):1557–66. https://doi.org/10.1007/s10973-018-7072-7.
Mladenovska K, Cruaud O, Richomme P, Belamie E, Raicki R, Venier-Julienne M-C, et al. 5-ASA loaded chitosan–Ca–alginate microparticles: preparation and physicochemical characterization. Int J Pharm. 2007;345(1):59–69.
Bunjes H, Unruh T. Characterization of lipid nanoparticles by differential scanning calorimetry, X-ray and neutron scattering. Adv Drug Deliv Rev. 2007;59(6):379–402.
Mura C, Nácher A, Merino V, Merino-Sanjuan M, Manconi M, Loy G, et al. Design, characterization and in vitro evaluation of 5-aminosalicylic acid loaded N-succinyl-chitosan microparticles for colon specific delivery. Colloids Surf B. 2012;94:199–205.
Heurtault B, Saulnier P, Pech B, Proust J-E, Benoit J-P. Physico-chemical stability of colloidal lipid particles. Biomaterials. 2003;24(23):4283–300.
Chantaburanan T, Teeranachaideekul V, Chantasart D, Jintapattanakit A, Junyaprasert VB. Effect of binary solid lipid matrix of wax and triglyceride on lipid crystallinity, drug-lipid interaction and drug release of ibuprofen-loaded solid lipid nanoparticles (SLN) for dermal delivery. J Colloid Interface Sci. 2017;504:247–56.
Souto EB, Mehnert W, Muller RH. Polymorphic behaviour of Compritol888 ATO as bulk lipid and as SLN and NLC. J Microencapsul. 2006;23(4):417–33. https://doi.org/10.1080/02652040600612439.
Ruktanonchai U, Limpakdee S, Meejoo S, Sakulkhu U, Bunyapraphatsara N, Junyaprasert V, et al. The effect of cetyl palmitate crystallinity on physical properties of gamma-oryzanol encapsulated in solid lipid nanoparticles. Nanotechnology. 2008;19(9):095701.
The authors wish to thank Conselho Nacional de Desenvolvimento Científico e Tecnológico –CNPq (Processes #443238/2014-6 and #470388/2014-5) for their financial support. This work was also financed through the project M-ERA-NET/0004/2015 from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) from national funds, and co-financed by FEDER, under the Partnership Agreement PT2020.
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Silveira, E.F., Rannier, L., Nalone, L. et al. Loading of 5-aminosalicylic in solid lipid microparticles (SLM). J Therm Anal Calorim 139, 1151–1159 (2020) doi:10.1007/s10973-019-08544-7
- Solid lipid microparticles
- Cetyl palmitate
- 5-aminosalicylic acid