The aim of this research were to prepare CI-921 mixed micelles(CI-Micelles), to establish a method for determining the entrapment efficiency of CI-Micelles, to optimize the formulation and to evaluate their in vitro properties. CI-Micelles were prepared by film dispersion. Dialysis and fitting were used to calculate true entrapment efficiency(EE)and drug loading(DL)of CI-Micelles. The influences of polymer concentration, polymer radio and hydrating media on the entrapment efficiency, drug loading and particle-size were investigated. The stability at 4 °C in 6 days was evaluated. The optimal formulation of CI-921-Micelles consisting of polymer concentration of 72 mg/mL, a mass radio of Pluronic F127/Solutol HS15 at mass ratio of 1 ∶2 and 5% glucose solution as hydrating medium, showed a EE of more than 90%, and mean particle-size of 17-25 nm and PDI< 0. 210. There were no significant changes to CI-Micelles in EE and particle-size after treatment at 4 °C for 6 days. The applied method of dialysis and fitting could be used to determine EE for micelles loaded with weakly basic drug which was difficult to meet sink conditions. Adjustment of the mass radio of Pluronic F127 to Solutol HS15 had resulted in uniform particle size distribution, high entrapment efficiency and drug loading capacity and better stability of CI-Micelles.

Background::The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori) infection status and CYP2C19 polymorphism on anaprazole. Methods::In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. Results::The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). Conclusions::The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.Registration::ClinicalTrials.gov, NCT04215653.