Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization and in vitro–in silico lung deposition results

Objective: The aim was to study the stability of dry powder inhaler (DPI) formulations containing antibiotic with different preparation ways – carrier-based, carrier-free, and novel combined formulation – and thereby to compare their physicochemical and in vitro–in silico aerodynamical properties before and after storage. Presenting a novel combined technology in the field of DPI formulation including the carrier-based and carrier-free methods, it is the most important reason to introduce this stable formulation for the further development of DPIs.

Methods: The structure, the residual solvent content, the interparticle interactions, the particle size distribution and the morphology of the samples were studied. The aerodynamic values were determined based on the cascade impactor in vitro lung model. We tested the in silico behavior of the novel combined formulated samples before and during storage.

Results: The physical measurements showed that the novel combined formulated sample was the most favorable. It was found that thanks to the formulation technique and the use of magnesium stearate (MgSt) has a beneficial effect on the stability compared with the carrier-based formulation without MgSt and carrier-free formulations. The results of in vitro and in silico lung models were consistent with the physical results, so the highest deposition was found for the novel combined formulated sample during the storage.

Conclusions: It can be established that after the storage a novel combined formulated DPI contained amorphous drug to have around 2.5?μm mass median aerodynamic diameter and nearly 50% fine particle fraction predicted high lung deposition in silico also.     

Controlled release antibiotics for dry powder lung delivery

Introduction: Two controlled release (CR) antibiotics intended for inhalation therapy were evaluated. Material and Methods: Ciprofloxacin and doxycycline (both hydrochlorides) were selected as model drugs. Microparticles containing 90:10 ratio of polyvinyl alcohol (PVA) and single antibiotics or combinations were obtained via spray drying. The microparticles were evaluated in terms of particle size, morphology, thermal properties, aerosol performance, and in vitro release. Results and Discussion: Analysis of the microparticle morphology indicated comparable size distributions (2.04 ± 0.06, 2.15 ± 0.01, and 2.21 ± 0.01 μm for ciprofloxacin, doxycycline, and co-spray-dried antibiotic formulations, respectively). Thermal analysis of the microparticles suggested similar responses, which were dominated by the endothermic peaks observed for PVA alone. Analysis of the aerosol performance suggested that the individual antibiotic formulations had different aerosol profiles that were dependent on the antibiotic used. In comparison, the combination CR antibiotics had identical aerosol profiles, suggesting that the microparticles were homogeneous. The release of antibiotics from the CR microparticles showed that ≤50% was released over a 6-hour period in comparison to ≥90% being released in the first hour for microparticles containing no PVA. Conclusions: The potential for antibiotic therapy, and specifically CR antibiotic therapy using dry powder inhalers, provides a promising route for the treatment of pulmonary infection.     

环丙沙星降解菌的筛选及其降解特性探究

为获取一株有效降解环丙沙星的菌株,并探究其在降解过程中的降解特性,利用高效液相色谱法筛选环丙沙星降解菌,根据菌落形态、生理生化特性以及16S rDNA基因序列分析,对降解菌进行鉴定;并研究菌株活性、胞内外物质以及细胞壁对质量浓度为4 μg/mL环丙沙星的降解作用。结果表明,罗伊氏乳杆菌WQ-Y1在物理吸附和生物降解的共同作用下,降解率最高可达70.2%,其胞内物质、胞外物质以及细胞壁对环丙沙星的降解率分别为17.7%、23.4%和37.0%,远低于活菌的降解率。可见罗伊氏乳杆菌WQ-Y1对环丙沙星的物理吸附作用和菌株体内的酶都并非是菌株降解环丙沙星的单一途径,而是依赖于完整的菌株活性。     

Removal of ciprofloxacin from aqueous solution using wheat bran as adsorbent

Current study describes sorption of antibiotic drug (ciprofloxacin) by using nontoxic and biocompatible carrier, i.e., wheat bran (WB). For sorption study, various parameters were optimized and Freundlich, Dubinin–Radushkevich, Langmuir, and Temkin isotherm models were applied to demonstrate the mechanism of sorption, while kinetics study for sorption was evaluated using diffusion models, pseudo-first-order kinetic (Langergren) and pseudo-second-order (Ho and McKay) kinetic models. In addition, thermodynamics study was also carried out. However, sorption of ciprofloxacin was pH depended and it showed 75% drug release in alkaline medium (at pH = 1.5) indicating the good release ability of WB for ciprofloxacin.     

Dual Escherichia coli DNA Gyrase A and B Inhibitors with Antibacterial Activity

The emergence of multidrug-resistant bacteria is a global health threat necessitating the discovery of new antibacterials and novel strategies for fighting bacterial infections. We report first-in-class DNA gyrase B (GyrB) inhibitor/ciprofloxacin hybrids that display antibacterial activity against Escherichia coli. Whereas DNA gyrase ATPase inhibition experiments, DNA gyrase supercoiling assays, and in vitro antibacterial assays suggest binding of the hybrids to the E. coli GyrA and GyrB subunits, an interaction with the GyrA fluoroquinolone-binding site seems to be solely responsible for their antibacterial activity. Our results provide a foundation for a new concept of facilitating entry of nonpermeating GyrB inhibitors into bacteria by conjugation with ciprofloxacin, a highly permeable GyrA inhibitor. A hybrid molecule containing GyrA and GyrB inhibitor parts entering the bacterial cell would then elicit a strong antibacterial effect by inhibition of both the GyrA and GyrB subunits of DNA gyrase and potentially slow bacterial resistance development.     

环丙沙星-铜配合物紫外分光光度法测金属硫蛋白

在pH=6的BR缓冲溶液中,环丙沙星-铜配合物与金属硫蛋白作用,导致体系吸光强度增强,在272 nm波长处,吸光强度与金属硫蛋白的浓度呈线性关系,据此建立了测定金属硫蛋白的新方法。方法的线性范围为0.259～1.54μmol/L,检出限7.76×10-8mol/L,样品平均加标回收率为91.8%。本方法操作简便、快速,灵敏,可用于实际样本测定,结果满意。     

荧光光度法测定鱼肉中的环丙沙星

采用荧光光度法测定了鲫鱼、鳗鱼、鲤鱼和罗非鱼肌肉组织中的环丙沙星药物残留量。样品用酸性乙腈提取,正己烷脱脂,水相在HAc-NaAc(pH4.5)缓冲溶液中,激发波长λex275nm,荧光测定波长λem450nm下用荧光光度法测定环丙沙星含量,环丙沙星的线性范围10￣150μg/L,相关系数r=0.9987,检出限为5μg/L。回收率为74.0%￣90.6%。变异系数为2.96%￣7.54%。