Actually, many strategies are studied to propose dosage forms adapted to the hydrophobicity of various Active Pharmaceutical Ingredients (API). An alternative solution to synthetic coating is the use of biopolymers as potential matrices for controlled and sustained delivery. In this way, vegetable proteins offer interesting functional properties as encapsulating materials of hydrophobic API, mainly due to their amphiphilic characteristic. Moreover, their properties could be improved thanks to suitable chemical modification of proteic chains. The objective of this work was to modulate the pH sensitivity of soy protein isolate (SPI) via two chemical modifications: acylation and succinylation, in order to increase protein hydrophobicity and formulate enteric microparticulate forms for oral controlled delivery. In this study, ibuprofen (IBU) was chosen as a model hydrophobic drug. Acylation was performed according to the Schotten-Baumann reaction with dodecanoyl chloride at the molar ratio (C12)/NH2 (2/1). An acylation rate of 37.3% was obtained. Succinylation was carried out using a succinic anhydride/soy protein molar ratio of 1.5, to obtain a 94% of succinylation rate. Proteins solubility profiles at different pH range showed that both modifications reduced protein solubility in acid medium. Microparticles were prepared at different ratios (%) of SPI or modified soy protein isolate / IBU: 90/10, 80/20 and 60/40, using spray-drying process. IBU concentration was measured by HPLC and microparticles characterization included particle size distribution, SEM and TGA analysis. Spray-drying yields higher than 70% and high microencapsulation (ME) efficiencies (all higher than 80%) were obtained for the different proteins. Drug release experiments were performed under conditions recommended by the European Pharmacopoeia. For simulated gastric fluid (pH 1.2 with pepsin), a low release was observed, especially with modified proteins microparticles. Kinetics at simulated intestinal fluid (pH 6.8) presented a quick release (100% in 90 min). In conclusion, both modifications improved interactions between IBU/protein, increasing the affinity for hydrophobic API and higher ME efficiency were obtained, confirming taht vegetable proteins can be valorized as encapsulate excipient for hydrophobic API and enteric formulations.

Modified soy protein as encapsulate excipient in pharmaceutical applications

253rd National Meeting (2017)

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