Preparation,Characterization, and Pharmaceutical Application of Linear Dextrins. I. Preparation and Characterization of Amylodextrin,Metastable Amylodextrins,and Metastable Amylose

The linear dextrin amylodextrin was prepared by enzymatic hydrolysis from waxy maize. Four metastable amylodextrins were prepared by complexation with different volatile organic compounds. All products showed partial dissolution into water at room temperature, because of dissolution of molecules with a lower DP. X-ray diffractometry revealed a helical conformation with six glucose units per turn for amylodextrin and metastable amylodextrins prepared with small molecules, and a helical conformation with seven glucose units per turn for metastable amylodextrins prepared with larger molecules. All metastable amylodextrins showed a helix with reduced distance between two turns as compared to amylodextrin. Metastable amylose, prepared from Amylose V, showed a helical conformation again with a reduced distance between two turns compared to Amylose V. FTIR analysis indicated a more flexible conformation for Amylose V and metastable amylose than for the amylodextrins.     

Preparation,Characterization, and Pharmaceutical Application of Linear Dextrins. III. Drug Release from Fatty Suppository Bases Containing Amylodextrin

Drug release from fatty suppository bases containing a solid dispersion of diazepam with amylodextrin or a complex of prednisolone with amylodextrin was analyzed in a flow-through model. Being present as a suspension in the fatty base, particles of complex or solid dispersion are transported to the lipid–water interface by sedimentation. After entering the aqueous phase they partially dissolve. The suppositories showed increased drug release compared with the corresponding suppositories containing drug only. Because of the partial solubility of amylodextrin, drug release was lower than the release from drug–cyclodextrin complexes. Use of the soluble fraction of amylodextrin for both the solid dispersion and the complex further enhanced drug release, but it was still below that of drug–cyclodextrin complexes.     

Increased Stabilizing Effects of Amphiphilic Excipients on Freeze-Drying of Lactate Dehydrogenase (LDH) by Dispersion into Sugar Matrices

Purpose. The stabilizing effect of amphiphilic excipients and sugars against protein inactivation during freeze-drying was studied in relation to their physical states in freeze-dried cakes. Methods. Physical states of amphiphilic excipients were studied by powder X-ray diffractometry and differential scanning calorimetry (DSC). Stabilizing effects of excipients were studied using lactate dehydrogenase (LDH) as a model protein. Results. Although poly(ethylene glycols) (PEGs) 1000 to 20000 crystallized when freeze-dried alone, the addition of sugars decreased their crystallinity by dispersing PEG into sugar-dominant matrices. Sugars species, molecular weight of PEGs, and buffer concentration also affected the crystallinity of PEGs. Sugars also dispersed some of other amphiphilic excipients, which tended to crystallize or become microscopically liquid when freeze-dried without sugar. Only the amphiphilic excipients that remained amorphous solid state protected the enzyme during freeze-drying in the absence of sugars. However, combinations of sucrose and all the amphiphilic excipients studied increased the stabilizing effects markedly. The remaining activities were greater than the sum of their individual ones. Conclusions. Various amphiphilic excipients are good stabilizers for freeze-drying of proteins when dispersed into sugar-dominant matrices.     

泮托拉唑钠肠溶固体分散体的制备及表征

采用溶剂冷冻干燥法制备泮托拉唑钠(1)肠溶固体分散体,并优化其处方工艺.运用鱼骨图分析法结合Plackett-Burman 设计(PBD),以在pH 6.8 介质中45 min 时的累积释放率为考察指标,从肠溶载体溶液pH 值、药物与肠溶载体的质量比、肠溶材料与冻干保护剂的质量比、搅拌速度、滤膜吸附作用、混合时间6 个...     

卡维地洛-PVPVA64固体分散体的制备与表征

目地：制备卡维地洛的固体分散体,提高其在水中的溶解度和溶出度。方法：以乙烯基吡咯烷酮／醋酸乙烯共聚物（PVPVA64）为载体,无水乙醇为溶剂,制备卡维地洛固体分散体,并通过差示扫描量热法、x-射线粉末衍射法、红外分光光度法、原子力显微镜扫描、溶解度测定、溶出度实验及稳定性试验对固体分散体进行表征。结果：差示扫描量热法、x-射线粉末衍射法以及原子力显微镜扫描的谱图和图像分析表明卡维地洛以无定形状态存在于制得的固体分散体中,而傅里叶变换红外光谱分析则表明在固体分散体中卡维地洛与PVPVA64间可能以氢键结合形式存在。与卡维地洛原料药相比,该固体分散体的溶解度提高了80倍,且1h溶出百分率也从10％以下提高到95．5％。经差示扫描量热法、x-射线粉末衍射法及溶出度实验考察发现,在温度为40℃、相对湿度为75％的环境条件下,于90d内,该固体分散体稳定性良好。结论：卡维地洛与PVPVA64形成固体分散体后可显著提高其溶解度和溶出度,且热力学稳定,可进一步用于制备生物利用度更高的口服固体剂型。     

大黄素固体分散体制备、表征与释药机制研究

目的 制备大黄素固体分散体,提高其体外溶出度并探究其释药机制。方法 采用分子对接技术,辅助筛选聚合物载体。以大黄素为原料药,Kollidon^® VA64为聚合物载体,采用热熔挤出工艺制备大黄素固体分散体。通过溶出仪测定其体外溶出,利用SEM、DCS和PXRD对原料药和固体分散体的表面形态和晶型进行表征,最后采用FTIR、NMR和分子动力学模拟对固体分散体的释药机制进行探究。结果 相较于大黄素原料药,大黄素固体分散体在4种介质中的溶出被明显改善,大黄素由结晶态转化为无定形态,药物与聚合物载体间形成了氢键。结论 固体分散体中药物晶型的转变和氢键的产生是改善药物体外溶出的主要因素。     

尼莫地平固体分散体的制备及其理化性质表征

目的 考察不同载体材料经双螺杆热熔挤出技术制备尼莫地平固体分散体的工艺参数、理化性质、增溶效果以及物理稳定性。方法 以共聚维酮和3个规格（L、M和H）的醋酸羟丙甲纤维素琥珀酸酯作为载体材料,使用双螺杆热熔挤出机制备尼莫地平固体分散体。使用偏光显微镜、差示热扫描量热分析和粉末衍射考察制得固体分散体的理化性质,使用原位光纤技术测定固体分散体的动力溶解度,并考察固体分散体的物理稳定性。结果 以共聚维酮为载体材料更容易进行热熔挤出操作,挤出过程螺杆扭矩值<30%,口模内熔体压力<15 bar;制得的固体分散体易于粉碎;过饱和度达到6 000 μg·mL^-1,且溶解迅速;同时在2个月加速条件下保持稳定。结论 共聚维酮更适合用做热熔挤出制备尼莫地平固体分散体的载体材料。     

微管蛋白抑制剂SUD-35固体分散体的制备、鉴定及初步体外药效学研究

目的将难溶性微管蛋白抑制剂SUD-35制备成固体分散体,以增加其溶解度及溶出速率。方法以聚乙二醇6000为载体,溶剂-熔融法制备SUD-35固体分散体。采用差示扫描量热分析与X-射线衍射观察药物在载体中的存在状态,并进行溶解度和体外溶出度研究。采用MTT法对SUD-35固体分散体对小鼠白血病L1210细胞药效进行测定。结果 SUD-35固体分散体中SUD-35的溶解度和溶出速率相对原料药和物理混合物均有明显提高,差示扫描量热分析与X-射线衍射结果显示SUD-35以无定型状态存在于固体分散体中,细胞药效结果显示SUD-35固体分散体对小鼠白血病L1210细胞增殖抑制率强于SUD-35纯药。结论聚乙二醇6000为载体制备SUD-35固体分散体,可显著提高SUD-35的溶解度及溶出速率。     

热熔挤出技术制备伊曲康唑固体分散体及体外溶出考察

以羟丙甲纤维素(HPMC E5)为分散载体,利用热熔挤出技术制备难溶性药物伊曲康唑固体分散体,并探究不同挤出工艺参数和增塑剂1,2-丙二醇(PG)含量对固体分散体溶出度的影响。结果表明,二次挤出制得的固体分散体中药物的溶出率大于直接挤出的固体分散体,且二者均明显大于物理混合物。使用PG作增塑剂后伊曲康唑固体分散体的溶出率得到了显著提高,当PG用量较高(10%)时,固体分散体在0.1 mol/L盐酸介质中的溶出率可达到93%。本研究可以为热熔挤出的工艺开发提供更多的思路,同时为进一步制备高规格(200 mg)伊曲康唑片剂提供帮助。