College of Pharmacy, Freie Universität Berlin, Berlin, Germany.
Eur J Pharm Biopharm. 2010 May;75(1):63-70. doi: 10.1016/j.ejpb.2010.01.006. Epub 2010 Jan 15.
The objective of this study was to improve the film formation and permeability characteristics of extended release ethylcellulose coatings prepared by dry polymer powder coating for the release of drugs of varying solubility. Ethylcellulose (7 and 10 cp viscosity grades) and Eudragit(R) RS were used for dry powder coating of pellets in a fluidised bed ball coater. Pre-plasticised ethylcellulose powder was prepared by spray-drying aqueous ethylcellulose dispersions (Surelease(R) and Aquacoat(R)) or by hot melt extrusion/cryogenic grinding of plasticised ethylcellulose. Chlorpheniramine maleate and theophylline were used as model drugs of different solubilities. The film formation process, polymeric films and coated pellets were characterised by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), scanning electron microscopy (SEM) and dissolution testing. Film formation and extended drug release was achieved with ethylcellulose, a polymer with a high glass transition temperature (T(g)) without the use of water, which is usually required in dry powder coating. DMA-measurements revealed that plasticised ethylcellulose had a modulus of elasticity (E') similar to the low T(g) Eudragit(R) RS. With increasing plasticiser concentration, the T(g) of ethylcellulose was reduced and the mechanical properties improved, thus facilitating coalescence of the polymer particles. SEM-pictures revealed the formation of a dense, homogeneous film. The lower viscosity grade ethylcellulose (7 cp) resulted in better film formation than the higher viscosity grade (10 cp) and required less stringent curing conditions. Successful extended release ethylcellulose coatings were also obtained by coating with pre-plasticised spray-dried ethylcellulose powders as an alternative to the separate application of pure ethylcellulose powder and plasticiser. The permeability of the extended release coating could be controlled by using powder blends of ethylcellulose with the hydrophilic polymer HPMC. In conclusion, dry polymer powder coating is an interesting technique to achieve extended release of drugs with varying solubility as an alternative to classical coatings obtained from organic polymer solution or aqueous polymer dispersions.
本研究旨在改善用于不同溶解度药物释放的缓释乙基纤维素包衣的成膜和渗透特性。乙基纤维素（7 和 10 cp 粘度等级）和 Eudragit（R）RS 用于在流化床球涂机中对丸剂进行干聚合物粉末包衣。通过喷雾干燥水性乙基纤维素分散体（Surelease（R）和 Aquacoat（R））或通过增塑乙基纤维素的热熔挤出/低温研磨制备预增塑乙基纤维素粉末。马来酸氯苯那敏和茶碱用作不同溶解度的模型药物。通过差示扫描量热法（DSC）、动态力学分析（DMA）、扫描电子显微镜（SEM）和溶解试验对成膜过程、聚合物膜和包衣丸进行了表征。使用具有高玻璃化转变温度（Tg）的乙基纤维素（一种通常在干粉包衣中需要使用水的聚合物）而无需使用水即可实现成膜和延长药物释放，这是一种聚合物。DMA 测量表明，增塑乙基纤维素的弹性模量（E'）与低 Tg 的 Eudragit（R）RS 相似。随着增塑剂浓度的增加，乙基纤维素的 Tg 降低，力学性能得到改善，从而促进了聚合物颗粒的聚结。SEM 图片显示形成了致密、均匀的膜。低粘度等级乙基纤维素（7 cp）比高粘度等级乙基纤维素（10 cp）更有利于成膜，并且需要不太严格的固化条件。通过使用预增塑喷雾干燥乙基纤维素粉末进行包衣，作为纯乙基纤维素粉末和增塑剂单独应用的替代方法，也获得了成功的缓释乙基纤维素包衣。通过使用乙基纤维素与亲水性聚合物 HPMC 的粉末混合物，可以控制缓释包衣的渗透性。总之，干聚合物粉末包衣是一种很有前途的技术，可以替代经典的从有机聚合物溶液或水性聚合物分散体获得的涂层，实现不同溶解度药物的延长释放。
