Spray-Dried Succinylated Soy Protein Microparticles for Oral Ibuprofen Delivery
- 82 Downloads
The potential value of succinylated soy protein (SPS) as a wall material for the encapsulation of ibuprofen (IBU), a model hydrophobic drug, by spray-drying was investigated. A succinylation rate of 93% was obtained for soy protein isolate, with a molar ratio of 1/1.5 (NH2/succinic anhydride). The solubility profile at 37°C showed that this chemical modification decreased the solubility of the protein below its isoelectric point, whereas solubility increased in alkaline conditions. Various SPS/IBU ratios (90/10, 80/20, and 60/40) were studied and compared with the same ratio of soy protein isolate (SPI/IBU). High encapsulation efficiency was achieved (91–95%). Microparticles were spherical and between 4 and 8 μm in diameter. The spray-drying of protein/IBU solutions appeared to be beneficial, as it resulted in an amorphous solid dispersion of IBU within the microparticles, coupled with an increase in the thermal stability of IBU. In vitro release was evaluated in acidic (pH 1.2 in the presence of pepsin) and neutral (pH 6.8) conditions similar to those in the gastrointestinal (GI) tract. IBU was released significantly more slowly at pH 1.2, for both proteins. However, this slowing was particularly marked for SPS, for which rapid (within 2 h) and complete release was observed at pH 6.8. These results validate the hypothesis that SPS is suitable for use as a coating material for hydrophobic active pharmaceutical ingredients (APIs) due to its pH sensitivity, which should delay IBU release in the gastrointestinal tract.
KEY WORDSplant protein succinylation green excipient microencapsulation oral route modified release pH sensitivity
The authors would like to thank the Mexican Council of Science CONACyT for providing financial support, Yannick Thébault and Cédric Charvillat from CIRIMAT for SEM and XRD analyses, and Christine Rey-Rouch from LGC for TGA analyses.
- 2.Boh B. Developements et applications industrielles des microcapsules. Microencapsulation: des sciences aux technologies. Paris: Lavoisier; 2007. p. 9–22.Google Scholar
- 4.O’Donnell KP, Williams RO III. Optimizing the formulation of poorly water-soluble drugs. Formulating poorly water soluble drugs: Springer; 2012. p. 27–93.Google Scholar
- 12.Mathiowitz E, Bernstein H, Morrel E, Schwaller K. Method for producing protein microspheres. Google Patents No. 5,271,961; 1993.Google Scholar
- 16.Anaya Castro MA, Alric I, Brouillet F, Peydecastaing J, Fullana SG, Durrieu V. Soy protein microparticles for enhanced oral ibuprofen delivery: preparation, characterization, and in vitro release evaluation. AAPS PharmSciTech. 2017:1–9.Google Scholar
- 19.Codex Alimentarius. Codex general standard for food additives. Codex STAN; 2008:192–1995.Google Scholar
- 26.International A. Official methods of analysis of AOAC International. Official methods of analysis of AOAC International. 1995;Volume II.Google Scholar
- 39.Liu Y, Wang X, Liu Y, Di X. Thermosensitive in situ gel based on solid dispersion for rectal delivery of ibuprofen. AAPS PharmSciTech. 2017:1–10.Google Scholar
- 43.Ogawa N, Hiramatsu T, Suzuki R, Okamoto R, Shibagaki K, Fujita K, et al. Improvement in the water solubility of drugs with a solid dispersion system by spray drying and hot-melt extrusion with using the amphiphilic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and d-mannitol. Eur J Pharm Sci. 2018;111:205–14.CrossRefGoogle Scholar