[Intranasal absorption of rivastigmine hydrogen tartrate and brain targeting evaluation].

To investigate factors influencing the intranasal absorption of rivastigmine hydrogen tartrate (RHT), we studied the pharmacokinetics of RHT after intranasal administration and evaluated its brain targeting behavior. In situ rat nasal perfusion model was used in the study and pH impact was examined on the intranasal absorption of RHT. High performance liquid chromatography (HPLC) method was established to measure RHT concentration in the plasma and brain tissue after intranasal and intravenous administration. The pharmacokinetic parameters, drug targeting index(DTI), and nose-to-brain direct transport percentage (DTP) were calculated. It was demonstrated that the intranasal absorption mechanism of RHT was passive diffusion. The absorption rate was highest at pH 6.0. The absolute bioavailability of intranasally administrated RHT was 73.58%. Compared with that of intravenous administration, RHT absorption into the brain was faster and more efficient after intranasal delivery, and the DTI value was 195.27% of intravenous injection. Moreover, 48.79% of the drug can be absorbed directly from the nose into the brain without systematic circulation. Meanwhile, drug elimination half-time in the brain was prolonged by 1.4 fold compared to that of intravenous injection. In conclusion, intranasal administration of RHT not only improves drug absorption into the system, but also enhances drug absorption rate and content in the brain remarkably, which is an advantage in the treatment of central nervous system-related diseases.

[Optimization and in vitro characterization of resveratrol-loaded poloxamer 403/407 mixed micelles].

The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.

[Recent progress of dry powder inhalation of proteins and peptides].

To provide theoretical and practical basis for the successful formulation design of physically-mixed inhalation dry powder of proteins and peptides, related references were collected, analyzed and summarized. In this review drug micronization technology and commonly used carriers for inhalation dry powder preparation were introduced. For proteins and peptides, supercritical fluid technology and spray-drying are more suitable because of their capabilities of keeping drug activity. Being approved by U. S. Food and Drug Administration, lactose has been extensively used as carriers in many inhalation products. Formulation and process factors influencing drug deposition in the lung, including carrier properties, drug-carrier ratio, blending order, mixing methods, mixing time and the interaction between drug and carrier, were elucidated. The size, shape and surface properties of carries all influence the interaction between drug and carrier. Besides, influence of micromeritic properties of the dry powder, such as particle size, shape, density, flowability, charge, dispersibility and hygroscopicity, on drug deposition in the lung was elaborated. Among these particle size plays the most crucial role in particle deposition in the lung. Moreover, based on the mechanisms of powder dispersity, some strategies to improve drug lung deposition were put forward, such as adding carrier fines, adding adhesive-controlling materials and reprocessing micronized drug. In order to design physically-mixed inhalation dry powder for proteins and peptides with high lung deposition, it is essential to study drug-carriers interactions systematically and illustrate the potential influence of formulation, process parameters and micromeritic properties of the powder.

[Preparation of budesonide sustained-release dry powder for inhalation and influence of lactose content].

Using high pressure homogenization method combined with spray-drying, budesonide-loaded chitosan microparticles were prepared and the in vitro release profile was investigated. The microparticles were then blended with lactose using a vortex mixer, influence of mixing speed, mixing time on drug recovery rate and content homogeneity were investigated. Meanwhile, influence of lactose content on drug recovery rate, content homogeneity, powder flowability and in vitro deposition were studied. It turned out that budesonide was released from the microparicles in a sustained manner, with fine particle fraction as high as 46.0%, but the powder flowability was poor. After blending with 10 times of lactose, the drug recovery rate was 96.5%, with relative standard deviation of drug content 2.5%, and fine particle fraction of the formulation increased to 59.6% with good flowability. It's demonstrated that using a vortex mixer, budesonide sustained-release dry powder for inhalation with good recovery and content homogeneity could be prepared, the formulation had good flowability and was suitable for pulmonary inhaling.

[Preparation of solid lipid nanoparticles by microemulsion technique].

AIM: To prepare solid lipid nanoparticles by microemulsion technique. METHODS: Stearic acid was used as the oil phase, lecithin as surfactant, alcohol as cosurfactant and distilled water as the aqueous phase. Microemulsion was prepared by mixing the above component in proper ratio. The corresponding pseudoternary phase diagram monitored Microemulsion formation field of different lecithin/alcohol. Solid lipid nanoparticles (SLN) were prepared by dispersing warm microemulsion in cold water under magnetic stirring. Then appropriate microemulsions that can contain more water phase and suitable oil phase were selected to prepare SLN. The influence of formulation, process variables on the preparation and quality of SLN were studied. Based on the investigation of single factors, orthogonal design was used to optimize SLN formulation and preparation process, and more, the reproducibility of the optimized results were studied. RESULTS: The results showed that the device temperature (Ti), water temperature (Tw), and delivery rate (Rd) were the key factors that influence the preparation process of SLN, and Tw was extremely important. The ratio of microemulsion formulation, the ratio of microemulsion and distilled water had also influence on its quality. CONCLUSION: Microemulsion technique can be used to prepare solid lipid nanoparticles.