氯高铁血红素胶囊溶出度测定方法的研究

目的研究氯高铁血红素溶出度测定方法。方法考察不同pH缓冲液和十二烷基硫酸钠对氯高铁血红素溶解速度的影响;建立了UV法测定氯高铁血红素的方法。结果通过实验,确定选用pH7.8缓冲液,并在其中加入5g·L-1的十二烷基硫酸钠作为溶出介质;建立了紫外法测定氯高铁血红素胶囊溶出度的方法,通过方法学考察,氯高铁血红素浓度在2~24mg·L-1范围内呈良好线性关系r=0.9999;辅料对吸收度无干扰,平均回收率为100.2%,RSD为0.61%;精密度、重现性均符合要求。结论说明所建立的方法简单可行,可以满足溶出度测定的需要。     

微粉化原料药的比卡鲁胺片的溶出度研究

目的：建立比卡鲁胺片溶出度试验的方法，并考察微粉化比卡鲁胺片溶出度的改善情况。方法：使用溶出度试验法Ⅱ法，采用紫外分光光度法测定溶出度。分别以pH6．8磷酸盐缓冲溶液和不同浓度的十二烷基硫酸钠溶液（0．1％，0．25％，0．5％，1％）为溶出介质，体积为1000mL，桨法，转速50r·min^-1，比较比卡鲁胺片的溶出行为。结果：经过气流微粉化加工成平均粒径为3．6μm的比卡鲁胺原料药压制成薄膜衣片自制片和进口片在上述溶剂中的溶出行为相似，而未经微粉化的自制片的溶出极差。结论：通过微粉化技术能够提高难溶性药物的溶出度，达到进口产品一样的效果。     

格列喹酮片的处方考查及溶出度测定

目的:研究难溶性药物格列喹酮的片剂工艺制备及提高溶出度测定结果的方法。方法:通过球磨机对原料进行不同程度的微粉化,通过三因素三水平正交设计法优化处方,并进行溶出度试验。结果:格列喹酮原料经过2、4和6h不同时间微粉化处理后进行观察,发现经4和6 h微粉化后其粒径能被控制在50μm以下,其中以4 h微粉化结果较好,不产生强吸附,易于进行制剂操作,且所制片剂较未微粉化原料所制片剂的溶出度有明显提高。结论:经4h微粉化处理格列喹酮后,粒径较小且可操作性强,明显提高了片剂的溶出度,工艺比较简单,适用于大生产。     

非诺贝特体外溶出度考察及其微粉化制剂的研究

目的考察不同厂家非诺贝特固体制剂体外溶出度以及微粉化对非诺贝特溶出度的影响。方法分别以 40 % (φ)乙醇溶液、5 0 % (φ)乙醇溶液、5g/L十二烷基硫酸钠溶液、1 0g/L十二烷基硫酸钠溶液为溶出介质 ,对 4种市售非诺贝特固体制剂的体外溶出度进行考察。采用球磨机制备微粉化非诺贝特 ,对其溶出度进行测定。结果 1 0 g/L十二烷基硫酸钠溶液中微粉化制剂的溶出速率明显快于其余 3种非微粉化制剂 ,初步探讨了非诺贝特固体制剂体外溶出度标准。用相似因子法对自制微粉化胶囊和法国生产的微粉化胶囊的溶出实验数据进行统计分析 ,结果表明两者溶出行为相似 ,相似因子f2 =72 4(5 0≤f2 ≤ 1 0 0 )。结论不同厂家非诺贝特固体制剂的溶出度差异较大 ,微粉化工艺能显著提高非诺贝特的溶出度     

Box-Behnken效应面法优化塞来昔布微粉化工艺

目的 采用气流粉碎技术进行塞来昔布微粉化试验研究,并对其体外溶出度进行考察。方法 通过对微粉化工艺参数优化,以粉碎压力(X₁,psi)、进料压力(X₂,psi)为考察对象,以D50(Y₁,μm)、D90(Y₂,μm)为评价指标,利用Box-Behnken效应面法优化微粉化工艺参数,采用Malvern粒度仪测定微粉化塞来昔布的粒径分布,扫描电镜考察其形态;并比较微粉化塞来昔布、参比制剂(西乐葆)和原料药的溶出速率和溶出量。结果 微粉化塞来昔布粒径D₅₀为1.07 μm,D90为3.71 μm,扫描电镜显示微乳粒径均一,制备的微粉化塞来昔布的体外累积溶出度明显高于原料药。结论 塞来昔布微粉化工艺采用Box-Behnken实验设计法优化简单、可行。     

不同固体制剂中白杨素的溶出度评价

目的考察白杨素不同固体制剂的体外溶出度,并建立白杨素制剂的溶出度HPLC测定方法。方法分别以体积分数40%和50%乙醇溶液,5和10g·L~(-1)十二烷基硫酸钠(SLS)溶液为溶出介质,对制备的3种白杨素固体制剂进行体外溶出度考察,并建立白杨素溶出度HPLC测定方法。结果 10g·L~(-1)十二烷基硫酸钠溶液更适合作为本研究中制备的3种白杨素固体制剂的溶出介质,白杨素微粉化胶囊剂的溶出度最高。此外,初步探讨了白杨素固体制剂体外溶出标准。结论不同制剂的白杨素溶出度差异较大,微粉化工艺能显著提高白杨素的溶出度。     

改善口服固体制剂溶出度的方法

溶出度是口服固体制剂的质量指标之一,用以保证药物吸收及生物利用度。改善溶出度主要依靠提高崩解度或释放度,药物微粉化或分布于载体以增加表面积及采用其它增溶措施。可选择适当的崩解剂、助溶或增溶性添加剂,改进混合、制粒等工艺和采用载体分散体系,通过器械粉碎或微粉化、微晶化处理以及采用喷雾干燥、冷冻干燥等。     

罗红霉素微粉化分散片的制备与溶出度测定

目的对罗红霉素微粉化分散片的制剂工艺和质量进行研究。方法使用球磨机制备罗红霉素-乳糖微粉化混合物,并添加适合的辅料制备分散片。结果所制样品质量稳定,分散均匀性及溶出度合格。结论本制剂设计合理,质量稳定。     

微粉化技术提高格列美脲片溶出度

目的:提高格列美脲片的体外溶出度。方法:用气流粉碎机制备微粉化物,HPLC法测定体外溶出曲线,与亚莫利片进行相似性比较。结果:微粉化物的D50粒径为1.026μm,3批片剂溶出度曲线相似因子为80。结论:微粉化可提高格列美脲片的体外溶出度,其溶出行为与参比制剂非常相似。     

非诺贝特微粉化片剂的研制

以乳糖和微晶纤维素作为主要辅料制备非诺贝特的微粉化物。并以此制备片剂。辅以预胶化淀粉调节片剂的溶出度。溶出度试验结果表明微粉化片溶出度达到中国药典普通片质量要求。比进口胶囊剂溶出速度快。初步稳定性试验结果表明分别在光照。75%相对湿度或40℃，10d下稳定。     

Increased Dissolution Rate and Bioavailability Through Comicronization with Microcrystalline Cellulose

Micronization is a commonly used enabling technology to improve the bioavailability of compounds where absorption is dissolution rate limited. However, decreasing particle size often results in increased Van der Waals' interactions and electrostatic attraction between particles. This causes agglomeration of particles, thereby compromising the increase in surface area gained by micronization. Comicronization with excipients has been reported to offer significant advantages over neat micronization. The present work describes the comicronization of a model compound CI-1040 at a high drug load that shows an increase in the dissolution rate and bioavailability in male Wistar rats. Physicochemical characterization of the comicronized and neat micronized material is presented to help explain the in-vitro and in-vivo data.     

Increased dissolution rate and bioavailability through comicronization with microcrystalline cellulose

Micronization is a commonly used enabling technology to improve the bioavailability of compounds where absorption is dissolution rate limited. However, decreasing particle size often results in increased Van der Waals' interactions and electrostatic attraction between particles. This causes agglomeration of particles, thereby compromising the increase in surface area gained by micronization. Comicronization with excipients has been reported to offer significant advantages over neat micronization. The present work describes the comicronization of a model compound CI-1040 at a high drug load that shows an increase in the dissolution rate and bioavailability in male Wistar rats. Physicochemical characterization of the comicronized and neat micronized material is presented to help explain the in-vitro and in-vivo data.     

氯化血红素固体分散物的研制及其分散特征评价

目的:探讨氯化血红素固体分散物的制备及其分散特征的评价.方法:采用溶剂熔融法制备氯化血红素固体分散物,用差示热量扫描(DSC)图谱、红外光谱、X-射线衍射图谱的变化鉴定药物在载体中的分散特征;并对其溶解度和累积溶出速率进行考察.结果:结果显示,以氯化血红素为主药,聚乙二醇6000(PEG6000)为载体制成的固体分散物中,氯化血红素是以分子状态分散在载体中;经溶解度和累积溶出速率的测定,固体分散物溶解度为原药的49倍,固体分散物较原药在30 min时的累积溶出速率提高了22倍.结论:制成固体分散物后,形成填充型固体溶液,氯化血红素的溶解度和溶出速率均得到显著提高,提示本工艺可行,同时也为氯化血红素新制剂的研究提供科学依据.     

当归超微粉的药剂学研究

目的:比较当归超微粉和普通粉的粉体学特征及溶出特点,探索超微粉碎技术在中药当归中的应用。方法:通过重压式超微粉碎机制备当归超微粉末;通过扫描电子显微镜(SEM)观察超微粉和普通粉的形貌和细胞特征,用激光粒度分析仪对2种粉末进行粒径分布测定,并对粉体学参数休止角和堆密度进行测定;采用高效液相色谱法测定阿魏酸的含量;用恒温搅拌溶出法对2种粉末主要成分溶出特点的关系进行研究。结果:当归超微粉和普通粉的粉体学特征、表面形态、溶出成分含量差异显著;通常情况下当归超微粉相应成分溶出的速度与浓度要高于普通粉。结论:微粉化能促进当归有效成分的充分利用,超微粉碎技术应用于当归具有可行性和必要性。     

原料药粒径对头孢地尼颗粒体外溶出行为的影响

目的：考察原料药粒径对头孢地尼颗粒体外溶出度的影响。方法参照2010版中国药典第二法,以 pH ＝6．8磷酸盐缓冲液为溶出介质,转速为50 r·min －1,采用紫外分光光度法为分析方法,考察不同粒径的原料制备的头孢地尼颗粒与参比制剂溶出的一致性。结果粒径为 D90：142．90μm、D50：30．25μm、D10：3．47μm（100目筛）和 D90：51．21μm、D50：10．71μm、D10：2．25μm（200目筛）的头孢地尼原料制成的颗粒溶出行为与原研不相似;在不同溶出介质中,D90：35．62μm、D50：6．98μm、D10：1．66μm 的头孢地尼原料制成的颗粒,与参比制剂的溶出行为均相似。结论建立的分析方法简单可靠,原料微粉化能够有效提高难溶性药物的溶出度。     

氯化血红素在β—环糊精包合前后溶解度和溶出度的研究

探讨氯化血红素用β－环糊精包合后的溶解度和体外溶出度,溶解度采用离心法,将氯化血红素及包合物用水配成饱和溶液,取适量以４００ｒ．ｍｉｎ＾－１离心,然后按分光光度法测定含量,溶出度采用桨法（中国药典二部二法）,以人工肠液为溶出介质,用分光光度法测定氯化血红素的含量。结果显示氯化血红素用β－环糊精包合后,溶解度和体外溶出度均有显著提高,制得的包合物水溶性好,体外溶出快,制备工艺简单易行。进一步证实包合物制备方法的可行性,同时也为氯化血红素加工成各种剂型开辟良好的前景。     

An overview on in situ micronization technique – An emerging novel concept in advanced drug delivery

The use of drug powders containing micronized drug particles has been increasing in several pharmaceutical dosage forms to overcome the dissolution and bioavailability problems. Most of the newly developed drugs are poorly water soluble which limits dissolution rate and bioavailability. The dissolution rate can be enhanced by micronization of the drug particles. The properties of the micronized drug substance such as particle size, size distribution, shape, surface properties, and agglomeration behaviour and powder flow are affected by the type of micronization technique used. Mechanical communition, spray drying and supercritical fluid (SCF) technology are the most commonly employed techniques for production of micronized drug particles but the characteristics of the resulting drug product cannot be controlled using these techniques. Hence, a newer technique called in situ micronization is developed in order to overcome the limitations associated with the other techniques. This review summarizes the existing knowledge on in situ micronization techniques. The properties of the resulting drug substance obtained by in situ micronization were also compared.     

Comparative Physicochemical Characterization of Phospholipids Complex of Puerarin Formulated by Conventional and Supercritical Methods

Purpose The aim of this work was to compare the physicochemical characteristics of the phospholipids complex of puerarin (Pur) prepared by traditional methods (solvent evaporation, freeze-drying and micronization) and a supercritical fluid (SCF) technology. The physicochemical properties of the pure drug and the corresponding products prepared by two different SCF methods were also compared. Methods Solid-state characterization of particles included differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), solubility, dissolution rate and scanning electron microscopy (SEM) examinations. Besides puerarin phospholipids complex (PPC) by four different methods, the solid-state properties of unprocessed, gas antisolvent (GAS) crystallized and solution enhanced dispersion by supercritical fluid (SEDS) precipitated puerarin samples were also compared. Crystallinity was assessed using DSC and XRPD. Drug-phospholipids interactions were characterized using Fourier transform infrared spectroscopy (FTIR). SEM was used to determine any morphological changes. Pharmaceutical performance was assessed in dissolution rate and solubility tests. Result The results of the physical characterization attested a substantial correspondence of the solid state of the drug before and after treatment with GAS technique, whereas a pronounced change in size and morphology of the drug crystals was noticed. The GAS-processed puerarin exhibited a better crystal shape confirmed by DSC, XRPD and IR. Polymorphic change of puerarin during SEDS coupled with the dramatic reduction of the dimensions determined a remarkable enhancement of its solubility and in vitro dissolution rate. Phospholipids complex prepared using supercritical fluid technology showed similar properties of physical state, thermal stability and molecular interaction with phospholipids (PC) to those of corresponding systems prepared by other three conventional methods namely solvent evaporation, freeze-drying and micronization as proved by XRPD, DSC, and FTIR. The best dissolution rate was obtained by SEDS-prepared complex, while the highest solubility was obtained for solvent evaporation method. Conclusion Supercritical fluid technology for the preparation of puerarin and its phospholipids complex has been proven to have significant advantages over the solvent evaporation technique and other conventional methods.     

双黄连口腔崩解片的制备及质量检查

目的:探讨双黄连口崩片制备工艺,优化口崩片处方。方法:以黄芩、金银花、连翘提取物为主药制备口崩片,采用单因素试验,考察崩解剂、起泡剂和压力对制备工艺的影响,以外观、崩解时限和黄芩苷、绿原酸、连翘苷的溶出度为指标考察制剂质量。结果:处方中各成分的质量分数分别为黄芩提取物14.7%、金银花提取物15.7%、连翘提取物16.3%、微晶纤维素18.0%、交联聚维酮15.7%、微粉硅胶0.43%、硬脂酸镁0.43%、甘露醇14.6%、无水枸橼酸2.5%、薄荷脑0.29%、碳酸氢钠0.63%、阿斯帕坦0.57%;制备的口崩片为褐色圆形片,崩解时限和溶出度均符合要求。结论:该制备工艺简便、准确,缓释效果理想,可为该制剂进一步研究提供理论依据。