Drug release from MCC- and carrageenan-based pellets: Experiment and theory

Microcrystalline cellulose (MCC) is a well-established pelletisation aid. However, MCC pellets generally do not disintegrate, resulting in prolonged drug release, especially in the case of drugs with poor/low aqueous solubility. The major objectives of this study were (i) to modify the prolonged matrix-type drug release from MCC pellets by addition of a disintegrant (croscarmellose Na) or pore former (PEG 6000), (ii) to evaluate carrageenan as potential alternative pelletisation aid for manufacturing high-dose immediate release pellets, and (iii) to better understand the underlying drug release mechanisms. Pellets containing 77–90% drug with poor/low aqueous solubility (vatalanib succinate, SAG/ZK, or theophylline) were prepared by extrusion–spheronisation. All batches showed acceptable yields, aspect ratios, tensile strengths, and porosities. Drug release from MCC pellets was predominantly controlled by pure diffusion and limited drug solubility and could be quantitatively described using Fick’s law. Importantly, the apparent drug diffusivity could effectively be adjusted by adding small amounts of a disintegrant or pore former, allowing for release periods ranging from a few minutes to several hours. The drug diffusion coefficients varied between 0.36 and 29 × 10⁻⁶ cm²/s. In contrast, carrageenan-based pellets very rapidly disintegrated upon contact with aqueous media and released high doses of drugs with poor/low aqueous solubility within a few minutes.     

HPLC法测定羚黄宝儿丸中盐酸小檗碱含量

目的建立HPLC法测定羚黄宝儿丸中盐酸小檗碱的方法。方法采用高效液相色谱法,色谱柱为Diamond C18（250nm×4．6nm,5μm）,流动相为乙腈-0．03mol／L磷酸二氢钾溶液（35：65）,流速为1．0ml／min,检测波长为345nm,柱温为室温。结果盐酸小檗碱线性范围为32．896-164．480μg／ml,平均回收率为99．81％,RSD为0．95％。结论本方法定量准确,重复性好,可以作为羚黄宝儿丸的质量控制方法。     

氧化苦参碱微丸的制备及其性质考察

目的:制备氧化苦参碱微丸并考察其性质。方法:用实验型低温挤出滚圆制粒机制备氧化苦参碱微丸;采用L9(34)正交设计优化工艺条件;考察不同含药量的微丸的粉体学性质及体外溶出度。结果:用挤出滚圆法制备的氧化苦参碱微丸圆整度好,大小均匀;最佳工艺为水∶微晶纤维素=0.90∶1,滚圆速度为35Hz,滚圆时间为5min,挤出速度为40Hz;体外溶出度在30min内达到75%以上。结论:挤出滚圆法制备氧化苦参碱微丸的工艺简便易行,制得的微丸质量好。     

药物制剂中薄膜包衣微丸的研究与应用

综述近年来薄膜包衣微丸在药物制剂中的研究与应用。微丸属于多单元型药物传递系统，具有众多优点。而将微丸制备技术和薄膜包衣技术相结合制成的具有特殊释药性质的薄膜包衣微丸，已经成为缓、控释制剂研究领域的热点。     

UPLC-MS/MS法同时测定通塞脉微丸中10种有效成分

目的 建立同时测定通塞脉微丸中10种有效成分（绿原酸、芹糖甘草苷、毛蕊异黄酮苷、木犀草苷、甘草苷、阿魏酸、异甘草苷、哈巴俄苷、甘草素和肉桂酸）的超高效液相色谱-串联质谱（UPLC-MS/MS）分析方法。方法 采用BEHC₁₈（100 mm×2.1 mm,1.7 μm）色谱柱,流动相为乙腈-0.1%甲酸水溶液,梯度洗脱,体积流量为0.3 mL/min,采用电喷雾电离源（ESI）,多反应离子监测（MRM）扫描方式进行检测。结果 10种成分线性关系分别为绿原酸Y＝294.09 X＋17 624;芹糖甘草苷Y＝19.296 X＋748.42;毛蕊异黄酮苷Y＝670.8 X＋11 121;木犀草苷Y＝490.45 X＋2 938.3;甘草苷Y＝33.489 X＋555;阿魏酸Y＝127.76 X＋1 343.5;异甘草苷Y＝57.87 X＋804.81;哈巴俄苷Y＝13.125 X－20.365;甘草素Y＝29.057 X＋367.71;肉桂酸Y＝72.867 X＋1 301.5,且各相关系数（r）均大于0.999 0。精密度、重复性和稳定性良好;加样回收率在96.00%～104.67%,RSD值均小于3%。结论 所建立的方法准确、快捷,重复性好,可用于通塞脉微丸中绿原酸、芹糖甘草苷、毛蕊异黄酮苷、木犀草苷、甘草苷、阿魏酸、异甘草苷、哈巴俄苷、甘草素和肉桂酸10种有效成分的同时测定。     

New insights on how to adjust the release profile from coated pellets by varying the molecular weight of ethyl cellulose in the coating film

The major aims of this work were to study the effect of the molecular weight (Mw) of ethyl cellulose (EC) on the drug release profile from metoprolol succinate pellets coated with films comprising EC and hydroxypropyl cellulose (HPC) with a weight ratio of 70:30, and to understand the mechanisms behind the different release profiles. A broad range of Mws was used, and the kinetics of drug release and HPC leaching followed. The higher the Mw of EC, the slower the HPC leaching and the drug release processes. Drug release occurred by diffusion through the pores created in the coating by the HPC leaching. A novel method was used to explain the differences in the release profiles: the effective diffusion coefficient (D_e) of the drug in the coating film was determined using a mechanistic model and compared to the amount of HPC leached. A linear dependence was found between D_e and the amount of HPC leached and, importantly, the value of the proportionality constant decreased with increasing Mw of EC. This suggests that the Mw of EC affects the drug release profile by affecting the phase separated microstructure of the coating and the hindrance it imparts to drug diffusion.     

Waxy Corn Starch: A Potent Cofiller in Pellets Produced by Extrusion–Spheronization

The purpose of this study was to assess the usefulness of waxy corn (maize) starch as a cofiller and diluent in pellets produced by aqueous extrusion–spheronization. Waxy corn starch was combined with microcrystalline cellulose (MCC) in the range of 20–50% of the entire composition. Pellets containing ordinary corn starch or lactose with MCC were used as reference. The shape of pellets was characterized using an optical microscopic image analysis system. The surface and cross-sectional structure were investigated by means of scanning electron microscopy (SEM). The replacement of ordinary corn starch by waxy corn starch made it possible to increase the amount of starch from 20 to 40%. The pellets containing 50% waxy corn starch were of poorer quality but superior to those containing 30% corn starch. The surface structure became slightly more irregular with respect to the amount of either starch, and a cavity was formed inside the pellet during the spheronization. The origin of starch did not affect the surface structure of the pellets. Waxy corn starch is a potential cofiller: the amount of MCC can be reduced in pellets produced by extrusion–spheronization by using waxy corn starch as a cofiller. This enables the reduction of the manufacturing cost of pellets with low drug load.