Pharmacokinetics and Safety of Rifamycin SV after Single and Multiple Doses of MMX® Modified Release Tablets in Healthy Male and Female Volunteers.

The primary objective of this single- and multiple-dose pharmacokinetic study was the investigation of rifamycin SV's pharmacokinetic profile in plasma and urine. All the 18 enrolled healthy men and post-menopausal women received modified release tablets containing 600 mg of the oral non-absorbable antibiotic, rifamycin SV, according to a multiple dose regimen: one tablet three times a day (daily intake: 1800 mg) for 14 consecutive days. Blood sampling and urine collection were performed up to 24 h post-dose after the first dose on Days 1 and 7. On average, on Day 1, Cmax,0-24 was 5.79 ± 4.24 ng/mL and was attained in a median time of 9 h. On Day 7, all the subjects had quantifiable levels of rifamycin SV in plasma at each sampling time. After a peak concentration attained 2 h post-dose (mean ± SD concentration: 10.94 ± 16.41 ng/mL), rifamycin SV decreased in plasma to levels similar to those of Day 1. The amounts of rifamycin SV excreted in urine paralleled the plasma concentration at the corresponding times. On Day 1, the total amount excreted in urine was 0.0013%, and was 0.0029% on Day 7. The study results confirmed those of the previous Phase I study: the systemic absorption of rifamycin SV was also proved negligible after 7 days of the 600 mg t.i.d. dose regimen of the newly formulated tablets, currently under development for the treatment of several small and large intestinal pathologies, including diarrhea-predominant irritable bowel syndrome, hepatic encephalopathy, and others. Registered at ClinicalTrials.gov with the identifier NCT02969252, last updated on 26JAN18.

Evaluation of Eleview® Bioadhesive Properties and Cushion-Forming Ability.

Submucosal injection is generally required for both endoscopic-mucosal resection (EMR) and submucosal dissection (ESD). SIC-8000 (Eleview®) is a new liquid composition in the form of a microemulsion for submucosal injection, approved by the Food and Drug Administration (FDA) 510(k) and Conformité Européene (CE) marked, containing a biocompatible polymer as a cushioning agent. The aim of this study was to evaluate Eleview®'s performance in terms of bioadhesive properties and cushion-forming ability. The bioadhesion was evaluated by measuring the interaction between Eleview® and the extracellular matrix (the main component of the submucosal layer) using the texture analyzer. To better comprehend the mechanism of action of Eleview® after submucosal injection, force of detachment and adhesion work were measured for the following formulations: Eleview®, Eleview® without poloxamer (functional polymer), poloxamer solution alone, normal saline, and MucoUp® (competing product on the Japanese market). The results obtained show the interaction between Eleview® and the extracellular matrix, highlighting the stronger bioadhesive properties of Eleview® compared with Eleview® without poloxamer, poloxamer solution alone, as well as normal saline and MucoUp®. The ability of Eleview® to form a consistent and long-lasting cushion in situ, once injected into the submucosal layer, was tested ex vivo on a porcine stomach. The results obtained show a better permanence in situ for the product compared with normal saline injection and to MucoUp® (t-test, p < 0.05).

An In Situ Gelling System for the Local Treatment of Inflammatory Bowel Disease (IBD). The Loading of Maqui (Aristotelia Chilensis) Berry Extract as an Antioxidant and Anti-Inflammatory Agent.

The aim of the present work was the development of an innovative in situ gelling system, to be applied on the mucosa of the distal colon via rectal route. The system consisted of three polymers having different functions: gellan (GG), able to jellify in presence of ions; methylcellulose (MC), a thermosensitive polymer with a gelation temperature close to 50 °C; and hydroxypropylcellulose (HPC), a mucoadhesive polymer. The three polymers were able to act synergistically, increasing the permanence of the vehicle on the mucosa and forming a protective gel layer. A DoE approach, "simplex centroid mixture design," was used to identify the optimal quantitative composition of the vehicle. The response variables considered were: vehicle viscosity at room temperature; increase in vehicle viscosity on increasing temperature (from room to physiological value) and upon dilution with simulated colonic fluid (SCF); and viscoelastic behavior, thixotropic area, and mucoadhesion properties of the gel formed at 37 °C upon dilution in SCF. The optimized vehicle was loaded with maqui berry extract (MBE), known for its antioxidant and anti-inflammatory properties. MBE loading (0.5% w/w) into the vehicle improved rheological and mucoadhesive properties of the formulation. Both MBE and the optimized vehicle were not cytotoxic towards human fibroblasts and Caco-2 cells. Moreover, the optimized vehicle did not affect MBE antioxidant properties.