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  • Title: Chitosan oligosaccharide as prospective cross-linking agent for naproxen-loaded Ca-alginate microparticles with improved pH sensitivity.
    Author: Čalija B, Milić J, Cekić N, Krajišnik D, Daniels R, Savić S.
    Journal: Drug Dev Ind Pharm; 2013 Jan; 39(1):77-88. PubMed ID: 22339172.
    Abstract:
    OBJECTIVES: The aim of the presented work was to develop Ca-alginate microparticles for oral administration of naproxen reinforced with chitosan oligosaccharide (COS) with a special interest to examine the potential of COS for improvement of microparticles stability in simulated intestinal fluid (SIF). METHOD: Microparticles were prepared according to the two-step procedure using an air-jet device with varying calcium chloride and COS concentration in the gelling medium. All prepared microparticles were subjected to size determination, morphology, surface, and inner structure analysis by scanning electron microscopy (SEM), drug loading (DL) and encapsulation efficiency (EE), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, in vitro swelling, and drug release studies. RESULTS: In general, COS-treated microparticles were spherical in shape but somewhat deformed, exhibiting the surface roughness with the mean particle size less than 350 µm. FT-IR and DSC studies confirmed the formation of polyelectrolyte complex (PEC) between alginate and COS, whereas chemical properties and crystalline state of naproxen were unaffected by the encapsulation process. Low naproxen solubility in the gelling medium and rapid entrapment resulted in high encapsulation efficiency (>80.0%). The results of swelling studies demonstrated that COS-treated particles were less sensitive to swelling and erosion in SIF in comparison to the nontreated particles. This resulted in prolonged drug release in SIF, which was dependent on the COS/alginate ratio. CONCLUSION: The obtained findings proved that COS could be used as an effective cross-linking agent for improvement of Ca-alginate microparticles stability in SIF, allowing prolonged release of the encapsulated drug after oral administration.
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