固体制剂干法包衣工艺的研究进展

固体制剂干法包衣工艺能够将我国的包衣工艺进行深化和提高,是非常重要的举措,因此固体制剂干法包衣工艺的发展空间非常广阔,本研究根据固体制剂干法包衣工艺研究的进展进行了分析,分析了几种较为常见的干法包衣技术,并分析了固体制剂干法包衣工艺的应用以及特点。     

口服缓控释制剂的研究与临床应用进展

大量阅读国内文献,对口服缓控释药物制剂进行研究分析。该制剂分为定速、定位和定时释放制剂,三类制剂各有特点并且互为补充。口服缓控释制剂在增加患者的顺应性、提高药物疗效、减少药物不良反应等方面发挥着重要作用,具有很强的临床实用性,但目前缓控释制剂的临床应用存在很多误区。     

长效干扰素研究进展

干扰素是一类多功能细胞因子,是由哺乳动物细胞受到适宜刺激产生的一种微量的、具高度生物学活性的蛋白质,具有抵抗病毒感染、抑制肿瘤生长和调节机体免疫功能的作用。干扰素α血浆半衰期短而丙型和乙型肝炎治疗周期长,影响了患者的依从性。目前延长蛋白药物半衰期的方法主要有化学修饰、蛋白融合、定点突变技术联合和改造药物制剂释放系统,随着又一新型长效干扰素ZALBIN即将上市,长效干扰素再次成为医药行业的聚焦点。现针对干扰素α长效制剂中的最新研究进展进行综述。     

PD-1/PD-L1免疫检查点抗体药物制剂稳定性开发

近年来抗体药物在生物医药领域发展迅速。随着抗体疗法种类的不断增加和PD-1/PD-L1靶点蛋白结构的确证,临床上,越来越多针对PD-1/PD-L1免疫检查点的单克隆抗体药物被不断开发并应用于治疗死亡率高、治愈率低的多种癌症中。但是抗体药物制剂开发水平还需进一步提高,一方面同一靶点的抗体产品同质化严重,另一方面抗体药物的理化性质比小分子药物复杂,因此需要针对不同单克隆抗体的药物特性,筛选出适应于临床应用的稳定蛋白制剂处方。概括了不同抗体药物制剂处方成分(缓冲液成分、药物辅料)的作用,结合PD-1/PD-L1靶点介绍了抗体药物制剂稳定性开发的一般策略以及CDE相关的审评要点。     

PD-1/PD-L1免疫检查点抗体药物制剂稳定性开发

近年来抗体药物在生物医药领域发展迅速。随着抗体疗法种类的不断增加和PD-1/PD-L1靶点蛋白结构的确证,临床上,越来越多针对PD-1/PD-L1免疫检查点的单克隆抗体药物被不断开发并应用于治疗死亡率高、治愈率低的多种癌症中。但是抗体药物制剂开发水平还需进一步提高,一方面同一靶点的抗体产品同质化严重,另一方面抗体药物的理化性质比小分子药物复杂,因此需要针对不同单克隆抗体的药物特性,筛选出适应于临床应用的稳定蛋白制剂处方。概括了不同抗体药物制剂处方成分(缓冲液成分、药物辅料)的作用,结合PD-1/PD-L1靶点介绍了抗体药物制剂稳定性开发的一般策略以及CDE相关的审评要点。     

甘草次酸结肠靶向微丸的研制

目的:确定甘草次酸结肠靶向微丸的制剂处方,评价其释药特性。方法:采用挤出-滚圆法制备甘草次酸素丸,利用流化床包衣技术对甘草次酸素丸进行包衣,用浆法评价微丸的体外释药性能。结果:采用微晶纤维素和甘草次酸,同时加入黏合剂羧甲基纤维素钠,经过充分搅拌混合,以30%的乙醇作为润湿剂,通过挤出-滚圆制得甘草次酸素丸。以尤特奇S100为膜控材料,加入适量柠檬酸三乙酯与滑石粉配制包衣液,对甘草次酸素丸进行包衣,制得甘草次酸包衣微丸。释放度实验表明甘草次酸素丸在其增重20%时,在0.1 mo L/L的盐酸溶液中不释放,在p H6.8的磷酸缓冲液条件下6 h内其释放率不到20%。而在p H7.4的磷酸缓冲液条件下2 h内释放率达到80%以上。结论:所制的甘草次酸素丸处方合理,制剂工艺简便,通过流化床包衣技术所制的甘草次酸包衣微丸在模拟的胃液中不释放,在小肠液中释放缓慢,在结肠液中释药良好,具有良好的结肠靶向作用。     

微生物学在制药专业中的重要性

制药专业的主要目标就是培养拥有基本制药知识,在生产生物药品、药物制剂、分析检验药品等方面都具备一定技术能力的高级药物应用人才。经过大量研究表明在制药专业中微生物学已经发挥了举足轻重的作用,因此只有积极穿插微生物学知识,才会将所学的制药专业知识融会贯通,获得满意的效果。本文主要分析了药理学中微生物学的重要性,药物制剂中微生物学的重要性,管理药品生产质量中微生物学的重要性,生物制药发酵技术中微生物学的重要性,分析检验药物技术中微生物学的重要性。     

拉曼技术在药物逆向工程中的应用

逆向工程以目标产品进行逆向分析及研究,是仿制药开发过程中的一个重要环节,在目前的仿制药一致性评价中发挥显著功效。 尽管物理、化学方法众多,但原研制剂的逆向工程分析仍然极具挑战、极其耗时。逆向工程的最终目的不仅是确定原研制剂中所有可能 的化学成分,还要深入揭示其制剂原则和药物释放机制。而如何高效合理地应用各种分析技术,是深入了解原研药的第一步。文章概述 了一种光谱技术——拉曼光谱在药物逆向分析工程中的实用性,特别介绍在某些情况下,当其他常用固态分析技术如 X 射线粉末衍射、 差示扫描量热法等不适用时,拉曼光谱对原研制剂中药物活性成分(API)晶型的鉴定。文章通过对拉曼光谱在某些特定条件下应用的具 体案例的演示,展示了分子振动相关光谱分析手段在药物逆向分析工程中的应用前景。     

药物制剂创新与发展趋势

随着生命科学．材料科学及信息科学的迅猛发展．各学科之问互相渗透,互相促进．大大推动了现代药剂学的发展与进步．使药剂学从经验探索阶段步入了科学研究阶段。药物制剂的新技术、新工艺、新辅料、新材料．新设备不断涌现,制剂基础研究不断深入．剂型与制剂设计理论不断完善,生产工艺技术不断发展与进步．今天的药物制剂已形成了4大类释药系统同时蓬勃发展的新局面．这些释药系统是：①普通释药系统．如片剂．胶囊剂、注射剂等;     

药物磷脂复合物工艺评价标准及应用研究进展

作为一种新型药物制剂技术,药物磷脂复合技术在天然药物、化妆品市场具有广泛的应用前景。本文概述了药物磷脂复合物的制备工艺,并根据药物溶解性综述了制备工艺的评价标准,以及磷脂复合物的应用前景。     

Evaluation of microencapsulation of a Bifidobacterium strain with starch as an approach to prolonging viability during storage

AIMS: To optimize a spray coating process for the production of encapsulated microspheres containing viable Bifidobacterium cells and to determine whether the readily gelatinized modified starch coating used in this study improved bacterial survival in foods or under acid conditions. METHODS AND RESULTS: An air inlet temperature of 100 degrees C was demonstrated to be optimal for the spray drying process, as it afforded good drying, low outlet temperatures (45 degrees C) and resulted in less than 1 log reduction in bifidobacteria numbers during drying. Maximum recovery yields of 30% were obtained after optimizing the air aspiration conditions. The average size of the Bifidobacterium PL1-containing starch microparticles was determined by scanning electron microscopy to be of the order of 5 microm. The starch-coated cells did not display any enhanced viability compared with free PL1 cells when exposed to acid conditions for 6 h or in two dry food preparations over 20 d storage at ambient temperature (19-24 degrees C). Determination of 1491 nucleotides of the 16S rRNA gene from PL1 indicated that it shared 97% homology with a previously sequenced Bifidobacterium ruminantium strain. CONCLUSIONS: Our data demonstrated that, although spray drying is a valuable process for encapsulating bifidobacteria, further work is required to ascertain a more appropriate coating material that will protect this strain against adverse environmental conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: The production of small, uniformly coated microspheres containing viable bifidobacteria using an affordable and industrially convenient process, such as spray drying, has commercial implications for the production of probiotic products. Although popular for use as a coating polymer by the food industry, this study indicated that modified starches might not be suitable for use as an encapsulating material for probiotic strains.     

A Statistical Approach to Optimize the Spray Drying of Starch Particles: Application to Dry Powder Coating

This article describes the preparation of starch particles, by spray drying, for possible application to a dry powder coating process. Dry powder coating consists of spraying a fine powder and a plasticizer on particles. The efficiency of the coating is linked to the powder morphological and dimensional characteristics. Different experimental parameters of the spray-drying process were analyzed, including type of solvent, starch concentration, rate of polymer feeding, pressure of the atomizing air, drying air flow, and temperature of drying air. An optimization and screening of the experimental parameters by a design of the experiment (DOE) approach have been done. Finally, the produced spray-dried starch particles were conveniently tested in a dry coating process, in comparison to the commercial initial starch. The obtained results, in terms of coating efficiency, demonstrated that the spray-dried particles led to a sharp increase of coating efficiency value.     

Feasibility of protein spray coating using a fluid-bed Würster processor

This article documents a feasibility study on coating fine powders with protein solutions using a Würster spray coater (GPCG-1 from Glatt Air Techniques, Ramsey, NJ). Spray coating was based on a fluid-bed process where fluidized microcarriers were coated inside the Würster column and dried in the fluidization chamber. Recombinant human deoxyribonuclease (rhDNase) was used as the model protein. Lactose powders of two different size ranges, 53-125 and 125-250 mum, were used as the model microcarrier. The amount of protein applied was varied to obtain coatings of varying thickness. The extent of rhDNase loading determined experimentally was found to be consistent with the theoretical value and was also confirmed visually by scanning electron microscopy. The coating showed a strong integrity after being subjected to mechanical force. However, the protein suffered serious aggregation during coating, most likely due to the thermal stress of the process. Aggregation was significantly reduced when rhDNase was formulated with calcium ions, consistent with the observation that Ca(2+) thermally stabilized the protein (as determined by scanning microcalorimetry) in aqueous solution. Thus, our study demonstrates that spray coating, particularly when used in conjunction with rational stabilization strategies, is a feasible alternative to other methods of preparing dried pharmaceutical proteins. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 560-566, 1997.     

Miniaturization in Pharmaceutical Extrusion Technology: Feeding as a Challenge of Downscaling

In recent years, extrusion technology has shifted the focus of pharmaceutical research due to versatile applications like pelletization, bioavailability improvement or manipulation of solid-state properties of drugs, continuous granulation, and the development of novel solid dosage forms. Meanwhile, a major effort has been devoted to the miniaturization of equipment in pharmaceutical extrusion technology, particularly with regard to the requirements of the development of new chemical entities and formulations. In the present study, a lab-scale twin-screw extruder was investigated in order to determine the limitations imposed by the feeding systems. The wet extrusion process was considered as challenging because both a powder and a liquid feeder have to be considered. Initially, the accuracy and uniformity of the powder and liquid feeder were tested independently of the extrusion process. After modification of the powder feeder, both feeders were investigated in conjunction with extrusion. Based on this, an optimization of the liquid feeder was required and completed. Both feeder modifications reduced the variability of the moisture content in the extrudates 10-fold. This led to a reliable small-scale extrusion process.     

Process Optimization of a Novel Immediate Release Film Coating System using QbD Principles

This work describes a quality-by-design (QbD) approach to determine the optimal coating process conditions and robust process operating space for an immediate release aqueous film coating system (Opadry® 200). Critical quality attributes (CQAs) or associated performance indicators of the coated tablets were measured while coating process parameters such as percent solids of the coating dispersion, coating spray rate, inlet air temperature, airflow rate and pan speed were varied, using a design of experiment protocol. The optimized process parameters were then confirmed by independent coating trials. Disintegration time of coated tablets was not affected by the coating process conditions used in this study, while tablet appearance, as determined by measurement of tablet color, coating defects and gloss was determined to be a CQA. Tablet gloss increased when low spray rate and low percent solids were used, as well as with increased coating pan speed. The study used QbD principles and experimental design models to provide a basis to identify ranges of coating process conditions which afford acceptable product quality. High productivity, color uniformity, and very low defect levels were obtained with Opadry 200 even when using a broad range of coating process conditions.     

Application of Quality by Design (QbD) Approach to Ultrasonic Atomization Spray Coating of Drug-Eluting Stents

The drug coating process for coated drug-eluting stents (DES) has been identified as a key source of inter- and intra-batch variability in drug elution rates. Quality-by-design (QbD) principles were applied to gain an understanding of the ultrasonic spray coating process of DES. Statistically based design of experiments (DOE) were used to understand the relationship between ultrasonic atomization spray coating parameters and dependent variables such as coating mass ratio, roughness, drug solid state composite microstructure, and elution kinetics. Defect-free DES coatings composed of 70% 85:15 poly(dl-lactide-co-glycolide) and 30% everolimus were fabricated with a constant coating mass. The drug elution profile was characterized by a mathematical model describing biphasic release kinetics. Model coefficients were analyzed as a DOE response. Changes in ultrasonic coating processing conditions resulted in substantial changes in roughness and elution kinetics. Based on the outcome from the DOE study, a design space was defined in terms of the critical coating process parameters resulting in optimum coating roughness and drug elution. This QbD methodology can be useful to enhance the quality of coated DES.KEY WORDS: biodegradable polymers, coating, drug-eluting stents, processing, quality by design     

Modeling weight variability in a pan coating process using Monte Carlo simulations

The primary objective of the current study was to investigate process variables affecting weight gain mass coating variability (CV _m) in pan coating devices using novel video-imaging techniques and Monte Carlo simulations. Experimental information such as the tablet location, circulation time distribution, velocity distribution, projected surface area, and spray dynamics was the main input to the simulations. The data on the dynamics of tablet movement were obtained using novel video-imaging methods. The effects of pan speed, pan loading, tablet size, coating time, spray flux distribution, and spray area and shape were investigated. CV _m was found to be inversely proportional to the square root of coating time. The spray shape was not found to affect the CV _m of the process significantly, but an increase in the spray area led to lower CV _ms. Coating experiments were conducted to verify the predictions from the Monte Carlo simulations, and the trends predicted from the model were in good agreement. It was observed that the Monte Carlo simulations underpredicted CV _ms in comparison to the experiments. The model developed can provide a basis for adjustments in process parameters required during scale-up operations and can be useful in predicting the process changes that are needed to achieve the same CV _m when a variable is altered.     

Industrially feasible alternative approaches in the manufacture of solid dispersions: A technical report

The purpose of this report was to compile relevant technical information on various alternative strategies that can be used as feasible approaches in the development of solid dispersions. The technologies discussed in the report are spray coating on sugar beads with a fluidized bed coating system, hot melt extrusion, direct capsule filling, electrostatic spinning, surface active carriers, and supercritical fluid technology. The focus is on basic principles, the equipment involved, and the relevant scale-up work. These technologies have been found to eliminate several drawbacks posed by the conventional methods of manufacturing of solid dispersions such as laborious preparation methods, reproducibility, scaling up of manufacturing processes, stability of drug, and vehicle.     

Konjac glucomannan hydrolysate: A potential natural coating material for bioactive compounds in spray drying encapsulation

This research aimed to develop a suitable coating material for encapsulating a plant bioactive compound via spray drying. A suitable process for modifying the rheological property of konjac glucomannan (KGM) solution by enzymatic treatment was developed. A plant bioactive compound, andrographolide, was selected to use as core material. Mannanase (1500 units of enzyme) was used in the treatment of KGM solution. The concentration of KGM solution was varied from 9 to 18% (w/w). It was found that 12% (w/w) was the optimum KGM concentration that could be hydrolyzed to a viscosity of <100 mPa·s. HPLC analysis of hydrolyzed solution found a fair amount of DP4–DP7 oligosaccharides (where DP is degree of polymerization) were obtained. The solution was then used as coating material in spray drying with inlet air temperature of 170°C and outlet air temperature of 85°C. It was found that 12% (w/w) konjac glucomannan hydrolysate (KGMH) was suitable for coating 2% (w/w) andrographolide. Its efficiency of encapsulation was also higher than that of KGMH combined with gamma‐cyclodextrin or beta‐cyclodextrin. This study revealed a great potential of using KGMH solution for pharmaceutical and food industries in the spray drying encapsulation process.     

Optimization study of doxorubicin liposomal preparations coated with laminin fragments

Immunoliposomes, coated with two peptide sequences and loaded with doxorubicin, were prepared. The influence of different parameters in the sequential steps of liposomal preparations was studied as, for instance, lipid composition, size reduction methods, elimination of non-entrapped drug, and peptide coating sequence. Results were evaluated, such as entrapment efficiency, phospholipid/drug and phospholipid/peptide relationship, and size of final preparations. Effective size reduction was only achieved through probe sonication and the presence of peptides on the surface of liposomes, which does not modify, significantly, the final phospholipid/drug relationship, related to the initial values; however, they promoted a slight increase in the size of final preparations. Dialysis was the most suitable method to wash liposomes from reactants, drug and peptides, as well as being the cleanest process to avoid microbial contamination without significant dilution. Peptide coating yields were similar for liposomal compositions presenting free carboxyl groups on the surface. As determined by other authors, the presence of polyethylene glycol monomethoxy chains on the surface reduces the reactivity of NPGE carboxylic groups.