Optimal Control of the Primary Drying Stage of Freeze Drying of Solutions in Vials Using Variational Calculus

The problem of operating freeze drying of pharmaceutical products in vials placed in trays of a freeze dryer to remove free water (in frozen state) at a minimum time was formulated as an optimal control problem. Two different types of freeze dryer designs were considered. In type I freeze dryer design, upper and lower plate temperatures were controlled together, while in type II freeze dryer design, upper and lower plate temperatures were controlled independently. The heat input to the material being dried and the drying chamber pressure were considered as control variables. Constraints were placed on the system state variables by the melting and scorch temperatures during primary drying stage. Necessary conditions of optimality for the primary drying stage of freeze drying process in vials are derived and presented. Furthermore, an approach for constructing the optimal control policies that would minimize the drying time for the primary drying stage was given. In order to analyze optimal control policy for the primary drying stage of the freeze-drying process in vials, a rigorous multi-dimensional unsteady state mathematical model was used. The theoretical approach presented in this work was applied in the freeze drying of skim milk. Significant reductions in the drying times of primary drying stage of freeze drying process in vials were obtained, as compared to the drying times obtained from conventional operational policies.     

β-环糊精-氧化石墨烯超分子杂化体的构筑及应用进展

β-环糊精是由7个D-吡喃葡萄糖单元通过α-1,4-糖苷键键连成环的超分子主体分子，“内疏水、外亲水”的独特结构赋予了其优异的分子识别能力；氧化石墨烯类材料凭借其优良特性成为近几年的研究热点。由β-环糊精和氧化石墨烯构筑的超分子杂化体在兼具二者特有性能的基础上又有新功能的引入。本文综述了β-环糊精-氧化石墨烯超分子杂化体的构筑方式，按二者间的连接方式，分别为共价键和非共价键两种连接方式，其中通过共价键连接是目前最主要的构筑方式；此外对β-环糊精-氧化石墨烯超分子杂化体的特征和表征进行了简述。同时对β-环糊精-氧化石墨烯超分子杂化体在水污染处理、电化学检测、药物控释和催化等领域的应用进展进行了综述。最后对该超分子杂化体在构筑和应用上的发展趋势进行了展望。     

脉冲微分方程理论在药物动力学中的应用研究

为了揭示药物在机体内的ADME过程,将脉冲微分方程理论应用于研究药物动力学若干问题中,通过对系统动力学行为的研究进而设计最佳用药方案,丰富了脉冲微分方程理论并对指导临床实践具有积极意义.     

口服制剂掩味方法的研究进展

综述了药物掩味方法的研究进展,对不同的技术进行了总结.开发药物制剂时,正确运用这些方法与技术,不影响药物的物理、化学稳定性和生物利用度.     

蛋白质药品冷冻干燥技术研究进展

冷冻干燥技术是制备固体蛋白质药品的常用方法。本文综述了蛋白质药品冻干保护机理、冻干工艺、冻干机的研究进展，并提出了优化药品冷冻干燥过程，提高药品的稳定性和经济性的研究思路。     

分子蒸馏技术的应用现状

介绍了分子蒸馏技术在热敏性有机化合物的提纯，食品和药物的浓缩，资源回收，产品的后处理等方面的应用现状和在我国的发展情况。     

Excipients in parenteral formulations: selection considerations and effective utilization with small molecules and biologics

Excipients form a major component of pharmaceutical formulations and are classified as any ingredient other than the active ingredient which is included within the product formulation to improve drug product performance. Functional uses of excipients include improving solubility and stability, safety and efficacy, as bulking agents in lyophilized formulations, tonicity agents, and aiding in controlled or prolonged drug delivery. Parenteral formulations are sterile, pyrogen-free; free of particulate matter and by-pass the body’s natural defense mechanisms. Excipients may demonstrate a synergistic effect when combined with an active ingredient but may also lead to unwanted reactions with the drugs and packaging components. Ideal excipients are required to be considered safe, inert and multifunctional. Contrary to the past, safety of excipients needs to be well established in order for their use in the pharmaceutical formulations. Therefore, careful consideration should be given while selecting an excipient. This review article provides an overview of the excipients used exclusively in small molecule and biological parenteral products including solutions, suspensions, and lyophilized formulations, information on the possible drug-excipient and drug-packaging interactions and the regulatory requirements for the use of pharmaceutical excipients. The readers will be able to have a comprehensive understanding of the excipients used in parenteral formulations.     

International Perspectives on Substantiating the Efficacy of Herbal Dietary Supplements and Herbal Medicines Through Evidence on Traditional Use

The efficacy of botanicals in medicines can be substantiated with evidence on traditional use, whereas in foodstuffs, this is often not possible. In Europe, for example, the evaluation and subsequent authorization of health claims on herbal dietary supplements (HDS) have been put on hold by the European Commission. This study aims to analyze the role of evidence on traditional use in international legal frameworks of foods and pharmaceuticals. Both legal sources as well as scientific studies offering insights into these regulatory frameworks were included into the analysis. The international approach toward evidence on traditional use for substantiating efficacy of botanicals varies highly. For herbal medicines, substantiating efficacy with evidence on traditional use is possible in all studied jurisdictions, except for Japan and the United States. HDS efficacy can only be substantiated with evidence on traditional use in India and New Zealand, although the enforcing authorities do not describe which data are required. Australia and Canada regulate botanicals in a separate “borderline” category from foods and pharmaceuticals. Both jurisdictions allow for substantiating efficacy with evidence on traditional use. This study's second objective was to assess the applicability of the international approaches in the European legal framework, in light of the ongoing political debate regarding the use of traditional evidence. Implementation of the analyzed international approaches would require major revisions of the current European legal framework. This review of international approaches might, however, aid in deciding upon future approaches for substantiating health claims with evidence on traditional use.     

Research progress on preparation of biomass-derived porous carbon and its adsorption of pharmaceuticals in wastewater

The rapid development of urban modernization and industrialization has caused increasingly serious pollution to the environment, especially water contamination. In recent years, the content of pharmaceuticals in industrial wastewater has increased year by year, and the pollution should not be ignored any more. Therefore, the development of new porous materials for the adsorption and separation of pharmaceutical molecules in wastewater has become a current research hotspot. This article summarizes the recent research on the adsorption and separation of pollutants in wastewater by biomass-derived porous carbons (biochars). First, it briefly introduces the treatment methods of pollutants in wastewater, and mainly focuses on the preparation and modification of biochars. Combined with the surface chemical properties and pore structure of the carbon materials, this paper summarizes and prospects the adsorption properties of biochar to pharmaceuticals.     

肠靶向海藻酸钙基微胶囊的制备及控释性能研究

利用毛细管共挤出技术结合静电吸附和仿生硅化的方法,制备了海藻酸钙-壳聚糖/精蛋白/二氧化硅(ACPSi)复合微胶囊。ACPSi复合微胶囊的平均粒径约3.18 mm,单分散性好,囊壁最外层的二氧化硅层可抑制其在肠液pH环境中的溶胀,增强囊的机械稳定性。将羟丙甲基纤维素邻苯二甲酸酯(HPMCP)肠溶微球作为释药“微阀门”,嵌入囊壁可以更好地控制微胶囊的释药行为。以吲哚美辛为模型药物,当药物浓度为22.5 mg/ml时,ACPSi载药微胶囊在pH 2.5模拟胃液中3 h时累计释药率仅为0.33%,而转移至pH 6.8模拟肠液中19 h时累计释药率为77.78%;囊壁嵌入HPMCP微球后,22 h时累计释药率可提高约4%。因此,该复合微胶囊具有良好的肠靶向作用和控释特性,作为口服肠靶向缓控释制剂具有良好的应用前景。