Hot melt extrusion: An application for enhancing drug solubility

Low aqueous solubility of API is a problem of drug product development.There are several methods to enhance drug solubility.Although drugs can increase solubility using many chemical and physical modifications,the few methods are able to enhance drug solubility for industrial scale[1].Hot-melt extrusion is one reliable process for enhancing drug solubility in a large scale production.It has been recognized as a one step process with several advantages.It can not only increase solubility of drug,but can also be used as a process to prepare controlled release dosage forms.Using a biodegradable polymer with hot-melt extrusion,the drug release of up to 1–6 months can be achieved[2].

Use of polymer combinations in the preparation of solid dispersions of a thermally unstable drug by hot-melt extrusion

The objective of the study was to prepare solid dispersions containing a thermally unstable drug by hot-melt extrusion(HME).Carbamazepine(CBZ)was selected as model drug and combinations of Kollidon VA64(VA64),Soluplus(SOL)and Eudragit EPO(EPO)were utilized as carriers.Preformulation was conducted to identify the suitability of polymer combinations based on solubility parameters,differential scanning calorimetry(DSC),hot stage microscopy and thermogravimetric analysis.Physicochemical properties of solid dispersions were determined by DSC,X-ray diffraction,fourier transform infrared spectroscopy,dissolution and accelerated stability testing.The results show that drug-polymer miscibility at temperatures below the melting point(Tm)of CBZ was improved by combining EPO with VA64 or SOL.With 30%drug loading in a solid dispersion in SOL:EPO(1:1,w/w),CBZ was mainly present in an amorphous form accompanied by a small amount of a microcrystalline form.The dissolution rate of the solid dispersion was significantly increased(approximately 90%within 5 min)compared to either the pure drug(approximately 85%within 60 min)or the corresponding physical mixture(approximately 80%within 60 min)before and after storage.The solid dispersion in SOL:EPO(1:1,w/w)was relatively stable at 401C/75%RH under CBZ tablet packaging conditions for at least 3 months.In conclusion,polymer combinations that improve drug-polymer miscibility at an HME processing temperature below the Tm of a drug appear to be beneficial in the preparation of solid dispersions containing thermally unstable drugs.

Compatibility and stability studies involving polymers used in fused deposition modeling 3D printing of medicines

One of the challenges in developing three-dimensional printed medicines is related to their stability due to the manufacturing conditions involving high temperatures.This work proposed a new protocol for preformulation studies simulating thermal processing and aging of the printed medicines,tested regarding their morphology and thermal,crystallographic,and spectroscopic profiles.Generally,despite the strong drug-polymer interactions observed,the chemical stability of the model drugs was preserved under such conditions.In fact,in the metoprolol and Soluplus®composition,the drug's solubilization in the polymer produced a delay in the drug decomposition,suggesting a protective effect of the matrix.Paracetamol and polyvinyl alcohol mixture,in turn,showed unmistakable signs of thermal instability and chemical decomposition,in addition to physical changes.In the presented context,establishing protocols that simulate processing and storage conditions may be decisive for obtaining stable pharmaceutical dosage forms using three-dimensional printing technology.

熔融沉积成型技术在药物制剂中的应用

FDA批准首个3D打印药物（左乙拉西坦速溶片,Spritam ）上市,开辟了3D打印技术在药物制剂应用中的新篇章。3D打印是一种以数字模型文件为基础,将可塑性的熔融材料逐层打印、叠加成型的方法,根据原材料及黏合原理的差异具有10余种不同的分类。本文选择目前应用最广泛的熔融沉积成型（FDM）技术,对其技术原理、载药方法及研究实例进行了总结,讨论了该技术在药物制剂应用中的优劣势。最后对FDM技术的未来发展进行了展望。

热熔挤出技术在缓控释给药系统中的应用进展

热熔挤出技术(HME)作为药物制剂技术领域的研究热点,具有药物分散效果好,无需使用有机试剂,可连续加工,自动化控制及工艺重现性高等优点。该技术在提高难溶性药物溶出度,掩味以及制备缓控释制剂方面具有突出优势。本文通过系统的文献调研,对HME在缓控释给药系统中的应用进展作一综述,为其在制药领域的应用发展提供参考。

不同药物及添加剂对Soluplus和Kollidon VA64玻璃化转变温度的影响

在热熔挤出过程中,载体材料的玻璃化转变温度是一个非常重要的工艺参数。本试验制备了不同比例药物或添加剂与Soluplus或Kollidon VA64的固态溶液,并进行差示扫描量热分析,从而考察不同物质(水分、灰黄霉素、利托那韦、胆固醇、改性大豆磷脂)对Soluplus及Kollidon VA64玻璃化转变温度的影响。结果表明,上述5种物质均能降低Soluplus及Kollidon VA64的玻璃化转变温度。其中,水分的存在能明显降低Soluplus及Kollidon VA64的玻璃化转变温度,且利托那韦、胆固醇的降低作用强于灰黄霉素及改性大豆磷脂。本研究为利用热熔挤出法制备辅料为Soluplus及Kollidon VA64的固体分散体提供了帮助。