热熔挤出技术制备吡罗昔康固体分散体

目的采用热熔挤出技术制备难溶性药物吡罗昔康固体分散体,来提高其溶出速率。方法以共聚维酮(PVP-VA64)为亲水性载体材料,聚乙二醇6000为增塑剂,采用热熔挤出技术制备吡罗昔康固体分散体。通过比较差示扫描量热图谱和累积溶出曲线,来表征和评价所制备的固体分散体。结果所制备的固体分散体溶出速率较物理混合物均显著提高。结论热熔挤出技术适用于制备吡罗昔康固体分散体,药物是以无定型分散在载体中,溶出度得到显著提高。     

热熔挤出法制备苯氧乙酸吡嗪酯类化合物FC固体分散体的研究

目的 利用热熔挤出法制备难溶性的药物苯氧乙酸吡嗪酯类化合物FC固体分散体,提高FC的溶出度.方法 选用亲水性的PVPK30、PEG6000、Poloxamer188作为载体辅料,采用热熔挤出技术制备FC固体分散体.通过比较药物FC在不同载体挤出物中的差示扫描量热图和累积溶出曲线图,来判断热熔挤出技术对提高难溶性药物FC溶出度方面的作用.结果 利用热熔挤出法制备的固体分散体能够显著的提高FC的溶出度.结论 用热熔挤出法制备的FC固体分散体,在提高难溶性药物的溶出度方面具有显著的作用.     

水飞蓟素胶囊溶出度一致性评价研究

考察试制品水飞蓟素胶囊在四种不同溶出介质中的溶出状况,对比参比药物作一致性评价研究,同时与原料药作比较,分别考察不同制剂在不同溶出介质中六种组份的溶出度改善与变化情况。结果显示,试制品与参比药物对比,各试验条件下,各组份f2因子均大于50,显示二者溶出度具有相似性。     

热熔挤出法制备联苯双酯固体分散体的工艺

目的应用热熔挤出技术制备难溶性药物联苯双酯(bifendate,DDB)的固体分散体,提高DDB的溶出度。方法以共聚维酮(S630)(PVP,N-乙烯基-2-吡咯烷酮和醋酸乙烯酯以质量比为60∶40的比例合成的水溶性共聚物)、PEG6000、丙烯酸树脂Ⅳ为亲水性载体辅料,采用同向双螺杆热熔挤出技术制备DDB固体分散体。比较不同载体挤出物的差示扫描量热图谱和累积溶出曲线,从而判断热熔挤出法对提高DDB溶出度方面的作用。结果采用热熔挤出技术制备的固体分散体可以显著的提高DDB的溶出度。结论采用HME方法制备DDB固体分散体可以显著提高药物的溶出度。     

国产与进口水飞蓟素片的溶出度研究

目的 :考察国产及进口水飞蓟素片的体外溶出条件。方法 :采用中国药典九五版规定的溶出度考察方法 ,以人工胃液、人工肠液为溶出介质进行溶出度研究。结果 :本文考察的几种水飞蓟素片的溶出度质量有较大差异 ,少数厂家的品种未能达到药典标准。结论 :有必要制定水飞蓟素的溶出度标准 ,提高国产水飞蓟素片的质量。     

水飞蓟素原料药及其制剂体外溶出的研究

目的考察水飞蓟素及其制剂(片剂和胶囊剂)的体外溶出度。方法参照美国药典桨法,以人工胃液(SGF)、模拟空腹状态下的肠流质(FaSSIF)、模拟进食状态下的肠流质(FeSSIF)为试验介质分别进行体外溶出实验,采用LC-ESI-MS技术测定水飞蓟素中3种主要成分(水飞蓟宁、水飞蓟宾A和水飞蓟宾B)的体外溶出度。结果水飞蓟素溶解度低,溶出慢,不同制剂在不同介质中的体外溶出速率存在差异,制剂的体外溶出与原料药物的溶出及溶解度有一定的相似性。结论制剂的溶出可以指导体内试验与临床用药,原料药物的溶出及溶解度测定可以指导制剂的溶出测定。     

共研磨法改善水飞蓟素固体分散体的溶出度

目的:通过共研磨技术改善水飞蓟素固体分散体的体外溶出度。方法:设计单因素试验考察溶出度的影响因素,如共研磨载体材料的种类及与共研磨药物的比例,研磨的时间等因素。结果:以甘露醇与PVP K30为混合亲水性载体材料,与药物的比例为1∶1∶1,研磨6 h,以pH7.4的磷酸盐缓冲溶液为溶出介质。结论:共研磨法制备水飞蓟素固体分散体能显著提高药物的体外溶出度,且制备工艺简单易行。     

依布硒固体分散体的制备及体外溶出度研究

目的提高依布硒的体外溶出速率。方法以固体分散技术制备依布硒固体分散体,并测定其体外溶出度,采用差示扫描量热法(DSC)进行物相分析。结果DSC分析表明,依布硒是以非晶体状态存在,用水溶性载体普朗尼克制备的分散体体外溶出60min大于60%。结论制备依布硒固体分散体可以提高其体外溶出度。     

热熔挤出法增加布洛芬的溶出度并掩盖其苦味

目的:制备布洛芬固体分散体,以增加布洛芬的溶出度并掩盖其苦味。方法:取布洛芬原料药与丙烯酸树脂Eudragit EPO,以1∶1.5(w/w)混合,采用热熔挤出法制备布洛芬固体分散体。用差示扫描量热法和粉末X射线衍射法分析布洛芬在Eudragit EPO中的分散状态。测定固体分散体、物理混合物和市售布洛芬片剂的溶出度,并评价布洛芬固体分散体的掩味效果。结果:布洛芬晶体结构的特征峰在差示扫描量热和粉末X射线衍射图中消失。在磷酸盐缓冲液中,固体分散体的溶出速度大于物理混合物和布洛芬片。志愿者对布洛芬固体分散体的味觉评价优于物理混合物和布洛芬原料。结论:热熔挤出法制备的Eudragit EPO固体分散体能增加布洛芬的溶出度,并有明显的掩味效果。     

水飞蓟素自乳化给药系统处方设计及溶出度评价

目的: 设计水飞蓟素自乳化系统处方并评价其溶出度.方法: 采用正交设计进行水飞蓟素自乳化系统处方设计,以溶解状况、乳化速度及透光率为指标进行综合评价,确定最佳处方.结果: 水飞蓟素自乳化系统除主药外,主要由吐温85、橄榄油、甘油组成.结论: 按最佳处方制备的水飞蓟素自乳化系统在人工胃液及人工肠液的溶出度均与德国的对照胶囊基本相同.     

热熔挤出技术在药物制剂中的应用进展

本文综述了作为一种新颖的药物制剂技术——热熔挤出技术的优势、工艺与设备,以及热熔挤出技术在药物制剂中的诸多应用,并对该技术的应用前景进行展望.     

流变学在热熔挤出制剂加工中的应用

热熔挤出作为一种新型的药物制备技术,在制药领域展现出诸多优势。本文就热熔挤出的技术原理、流变学基础、流变学在热熔挤出制剂加工中的应用以及挤出过程中常见问题进行综述。     

Residence time modeling of hot melt extrusion processes

The hot melt extrusion process is a widespread technique to mix viscous melts. The residence time of material in the process frequently determines the product properties. An experimental setup and a corresponding mathematical model were developed to evaluate residence time and residence time distribution in twin screw extrusion processes.The extrusion process was modeled as the convolution of a mass transport process described by a Gaussian probability function, and a mixing process represented by an exponential function. The residence time of the extrusion process was determined by introducing a tracer at the extruder inlet and measuring the tracer concentration at the die. These concentrations were fitted to the residence time model, and an adequate correlation was found. Different parameters were derived to characterize the extrusion process including the dead time, the apparent mixing volume, and a transport related axial mixing. A 2³ design of experiments was performed to evaluate the effect of powder feed rate, screw speed, and melt viscosity of the material on the residence time. All three parameters affect the residence time of material in the extruder.In conclusion, a residence time model was developed to interpret experimental data and to get insights into the hot melt extrusion process.     

Novel nicotinamide skin-adhesive hot melt extrudates for treatment of acne

ABSTRACT

Objectives: Hot melt extrusion is a continuous process with wide industrial applicability. Till current date, there have been no reports on the formulation of extrudates for topical treatment of dermatological diseases.

Methods: The aim of the present work was to prepare and characterize medicated hot melt extrudates based on Soluplus polymer and nicotinamide, and to explore their applicability in acne treatment. The extrudates were characterized using DSC, FTIR, XRD, and DVS. The extrudates were also tested for their skin adhesion potential, ability to deposit nicotinamide in different skin layers, and their clinical efficacy in acne patients.

Results: The 10% nicotinamide extrudates exhibited amorphous nature which was reserved during storage, with no chemical interaction between nicotinamide and Soluplus. Upon contrasting the skin adhesion and drug deposition of extrudates and nicotinamide gel, it was evident that the extrudates displayed significantly higher adhesion and drug deposition reaching 4.8 folds, 5.3 folds, and 4.3 folds more in the stratum corneum, epidermis and dermis, respectively. Furthermore, the extrudates significantly reduced the total number of acne lesions in patients by 61.3% compared to 42.14% with the nicotinamide gel.

Conclusion: Soluplus extrudates are promising topical drug delivery means for the treatment of dermatological diseases.     

Development and evaluation of lafutidine solid dispersion via hot melt extrusion: Investigating drug-polymer miscibility with advanced characterisation

In current study, immediate release solid dispersion (SD) formulation of antiulcer drug lafutidine (LAFT) was developed using hot melt extrusion (HME) technique. Amphiphilic Soluplus^® used as a primary solubilizing agent, with different concentrations of selected surfactants like PEG 400, Lutrol F127 (LF127), Lutrol F68 (LF68) were used to investigate their influence on formulations processing via HME. Prepared amorphous glassy solid dispersion was found to be thermodynamically and physicochemically stable. On the contrary, traces of crystalline LAFT not observed in the extrudates according to differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and Raman spectroscopy. Raman micro spectrometry had the lowest detection limit of LAFT crystals compared with XRD and DSC. Atomic Force microscopy (AFM) studies revealed drug- polymer molecular miscibility and surface interaction at micro level. 1H–COSY NMR spectroscopy confirmed miscibility and interaction between LAFT and Soluplus^®, with chemical shift drifting and line broadening. MD simulation studies using computational modelling showed intermolecular interaction between molecules. Dissolution rate and solubility of LAFT was enhanced remarkably in developed SD systems. Optimized ratio of polymer and surfactants played crucial role in dissolution rate enhancement of LAFT SD. The obtained results suggested that developed LAFT has promising potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of LAFT.