Stability and Release Kinetics of an Advanced Gliclazide-Cholic Acid Formulation: The Use of Artificial-Cell Microencapsulation in Slow Release Targeted Oral Delivery of Antidiabetics

Introduction: In previous studies carried out in our laboratory, a bile acid (BA) formulation exerted a hypoglycaemic effect in a rat model of type-1 diabetes (T1D). When the antidiabetic drug gliclazide (G) was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-cholic acid (G-CA), with good structural properties, excipient compatibility and exhibits pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH-controlled properties of this new formulation. The aim is also to examine the effect of CA on G release kinetics at various pH values and different temperatures. Method: Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, pH 3, pH 7.4 and pH 7.8 and temperatures of 20 and 30 °C. Results: The new formulation is further optimised by the addition of CA. CA reduced microcapsule swelling of the microcapsules at pH 7.8 and pH 3 at 30 °C and pH 3 at 20 °C, and, even though microcapsule size remains similar after CA addition, percent G release was enhanced at high pH values (pH 7.4 and pH 7.8, p < 0.01). Conclusion: The new formulation exhibits colon-targeted delivery and the addition of CA prolonged G release suggesting its suitability for the sustained and targeted delivery of G and CA to the lower intestine

Quantifying crystal form content in physical mixtures of (±)-tartaric acid and (+)-tartaric acid using near infrared reflectance spectroscopy

The objective of this study was to use diffuse reflectance near infrared spectroscopy (NIRS) to determine racemic compound content in physical mixtures composed primarily of the enantiomorph and to assess the error, instrument reproducibility and limits of detection (LOD) and quantification (LOQ) of the method. Physical mixtures ranging from 0 to 25% (±)-tartaric acid in (+)-tartaric acid were prepared and spectra of the powder samples contained in glass vials were obtained using a Foss NIRSystems Model 5000 monochrometer equipped with a Rapid Content Analyzer scanning from 1100 to 2500 nm. A calibration curve was constructed by plotting (±)-tartaric acid weight percent against the 2nd derivative values of log (1/R) vs λ at a single wavelength, normalized with a denominator wavelength (1480 nm/1280 nm). Excellent linearity was observed (R2=0.9999). The standard error of calibration (SEC) was 0.07 and the standard error of prediction (SEP) for the validation set was 0.11. Instrument and method errors for samples in the 2% composition range ((±)-tartaric acid in (+)-tartaric acid) were less than 1% RSD and 3% RSD, respectively. The practical LOD and LOQ were 0.1% and 0.5%, respectively, and comparable to the calculated LOD and LOQ. These studies show that NIRS can be used as a rapid and sensitive quantitative method for determining racemate content in the presence of the enatiomerically pure crystal in the solid-state

One-step twin-screw extrusion process of cellulose fibers and hydroxyethyl cellulose to produce fibrillated cellulose biocomposite

Abstract In this work, the defibrillation of cellulose fibers (CF) in the presence of hydroxyethyl cellulose (HEC) within the one-step twin-screw extrusion (TSE) process was examined. The effect of the TSE on cellulose fiber size reduction as well as CF-HEC biocomposites properties were investigated. The results showed that the TSE of cellulose fiber-hydroxyethyl cellulose (CF-HEC) with different cellulose fiber contents (50, 65, and 80 wt%) resulted in partial defibrillation of the cellulose fibers. The fractionation test of the cellulose fibers confirmed that their size was reduced and some fibrillation was observed in microscopy studies. The maximum width reduction of 46% occurred with 80 wt% cellulose content. However, the partial width reduction was also observed with 50% and 65 wt% of cellulose contents. Based on rheological measurements, the shear-viscosity trend of CF-HEC dispersion abruptly dropped when higher fiber content (80 wt%) was extruded, which was related to the fibrillation of the cellulose fibers as well as the reduction of the length. The extruded CF-HEC materials (powder form) were compression molded to prepare the biocomposites with different cellulose fiber contents (50, 65, and 80 wt%). The extruded CF-HEC powders were diluted with addition extra HEC to make biocomposites with lower fiber content (20%, 30%, and 40 wt%) and compression molded to study how the size reduction of the cellulose fibers affected the mechanical properties of biocomposites. The results showed that the E-modulus improved from 0.4 GPa of the neat HEC to 1.6 GPa for the composite with 40 wt% CF. Interestingly, the tensile strength of CF-HEC biocomposite with 40 wt% confirmed a clear improvement from 9.8 to 26.6 MPa, confirming good interaction between HEC and CF