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Loading of 5-aminosalicylic in solid lipid microparticles (SLM)

Solubility screening of lipid excipients and physicochemical characterization

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Abstract

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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Acknowledgements

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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Authors and Affiliations

  1. Program in Industrial Biotechnology, Laboratory of Nanotechnology and Nanomedicine (LNMED), Institute of Technology and Research (ITP), Tiradentes University (UNIT) - Aracaju/SEA, Av. Murilo Dantas, 300, Farolândia, Aracaju, SE, CEP 49.032-490, Brazil

    Elisânia F. Silveira, Lucas Rannier, Luciana Nalone, Ricardo L. C. A. Junior, Luiz P. da Costa & Patrícia Severino

  2. Institute of Technology and Research, Av. Murilo Dantas, 300, Aracaju, SE, CEP 49.032-490, Brazil

    Elisânia F. Silveira, Lucas Rannier, Luciana Nalone, Ricardo L. C. A. Junior, Luiz P. da Costa & Patrícia Severino

  3. Department of Exact and Earth Sciences, Federal University of São Paulo, Rua Arthur Riedel, 275, Diadema, 09972-270, Brazil

    Classius F. da Silva

  4. Laboratory of Biomaterials and Nanotechnology, University of Sorocaba, Rodovia Raposo Tavares km 92.5, Sorocaba, São Paulo, 18023-000, Brazil

    Marco V. Chaud

  5. Biochemistry and Tissue Biology Department, Institute of Biology, University of Campinas, Campinas, SP, Brazil

    Raquel de M. Barbosa

  6. Department of Pharmacy, Centro Universitário Mauricio de Nassau (UNINASSAU), Natal, RN, Brazil

    Raquel de M. Barbosa

  7. Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra (FFUC), Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal

    Eliana B. Souto

  8. CEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal

    Eliana B. Souto

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  1. Elisânia F. Silveira
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  2. Lucas Rannier
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  3. Luciana Nalone
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  4. Classius F. da Silva
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  6. Raquel de M. Barbosa
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  7. Ricardo L. C. A. Junior
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  9. Eliana B. Souto
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Correspondence to Eliana B. Souto or Patrícia Severino.

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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). https://doi.org/10.1007/s10973-019-08544-7

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