FORMULATION DEVELOPMENT OF FAMOTIDINE FLOATING TABLETS USING HOT-MELT EXTRUSION COUPLED WITH 3D PRINTING TECHNIQUE.

The main goal of this study is to develop a floating tablet of famotidine using hot melt extrusion coupled (HME) with Fused deposition modeling FDM 3D printing technology. Seventeen different formulations were prepared to obtain printable HME filaments. Hydroxypropyl cellulose (HPL-LF), hydroxypropyl cellulose (HPLC-EF), Hydroxypropyl Methylcellulose (HPMC-E5), and Ethyl Cellulose (EC) were used as polymeric carriers with 10% (w/w) famotidine. Polyethylene Glycol 1500 (PEG-1500) was used as a plasticizer. The resulting physical mixtures were then extruded using an 11 mm twin-screw co-rotating extruder (Thermo Fisher Scientific, Waltham, MA, USA). The HME filaments were then printed using an FDM-3D printer (Prusa i3 3D desktop printer, Prusa Research, Prague, Czech Republic) with a thickness of 0.4mm, line pattern, and 100% infill at 180 °C printing temperature. Famotidine, polymeric carriers, other excipient, filaments, and 3D printed tablets were analyzed to determine the physical state of famotidine by using a Differential Scanning Calorimetry (DSC). The in-vitro drug release profile of the printed tablets was evaluated. Five filaments (M10, M11, M15, M16, M17) out of seventeen were successfully printable. The tablets were printed in a line pattern and 100% infill with a hollow shape to have a low-density tablet that may reach the target of floating on the surface of the stomach for a more extended time. The famotidine DSC thermograms showed an endothermic melting peak at 163.5 °C. This endothermic peak disappeared in the extruded filament and the 3D-printed tablets. The disappeared peak indicates complete solubilization of famotidine in the polymeric carrier for all Five formulations. Drug content tests were performed from the best-printed tablets for M10, M11, and M17. The accepted formulations for further investigation were M10 and M17, respectively, which showed a release for 9 hours and 8 hours. The floating profile for M10, M11, and M17 was successful for around 8 hours. HME revealed the great potential to develop suitable filaments for FDM-3D printing. The formulation compositions and printing design and pattern are the keys to developing 3D printed floating tablets for famotidine

Cross-sectional correlates of increased IL-18 but reduced fetuin-A and oxytocin with adiposity and blood indices in metabolic syndrome patients with and without prediabetes

Background: Oxytocin (OXT), fetuin-A and interleukin-18 (IL-18) are involved in the development and progression of metabolic syndrome (MetS) and prediabetes (pre/T2DM). Aims, participants and methods: This study aimed to compare and correlate the plasma levels of OXT, fetuin-A and IL-18 with clinical parameters, haematological indices and adiposity indices in Jordanian MetS subjects. In a cross-sectional study, 30 normoglycaemic lean study participants (control), 30 MetS study participants, and 29 MetS pre/T2DM study participants were recruited. Results: Median circulating levels of both OXT and fetuin-A were lower in MetS and MetS pre/T2DM versus control group. OXT (pg/ml; median interquartile range): MetS 1975.4 and MetS pre/T2DM 1403 versus control 4176.6 ( p = 0.009 and p = 0.001, respectively). For fetuin-A (ng/ml), MetS (5784) and MetS pre/T2DM (2154) were lower versus control (6756.3) ( p = 0.040 and p = 0.007, respectively). Neither biomarker was described as substantially different in MetS versus MetS pre/T2DM ( p = 0.071 and p = 0.155, respectively). Conversely, a non-significant increase in IL-18 was observed in the MetS and MetS pre/T2DM groups compared to normoglycaemic lean controls (232 and 287.5, p > 0.05 versus 108 for both). In addition, conicity index (C-index), atherogenicity index (TG-HDL-C), waist to hip ratio, mean platelet volume (MPV; fl) and red cell distribution width (RDW-CV%) in both MetS and MetS pre/T2DM were significantly higher ( p < 0.001) versus controls. However all above MetS-related indices were not ascribed any statistically marked variation in the MetS group when compared to the MetS pre/T2DM group. Both total study pool of recruits’ fetuin-A (Spearman r = – 2.66, p = 0.049) as well as MetS pre/T2DM group IL-18 (Spearman r = 0.380, p = 0.046) were inversely correlated with RDW-CV%. OXT in MetS inversely correlated with waist circumference/hip circumference ratio (Spearman r = −0.387, p = 0.038). No other pronounced associations between biomarkers could be detected in any study arm. Conclusion: These findings substantiate the clinical relevance and significance of OXT, fetuin-A and IL-18 as surrogate screening/prognostic tools and therapeutic targets to predict/prevent metabolic dysregularities and anomalies