薄膜包衣过程中容易出现的问题及解决方法

薄膜包衣是采用符合包衣要求的高分子聚合物做衣料,以有机溶媒溶解喷在片剂表面,蒸发后片剂表面形成一层膜为薄膜衣。薄膜包衣主要与以下三个因素有关:1 片芯问题     

氨氯地平混悬液包衣替米沙坦片芯的制备

目的 采用氨氯地平混悬液包衣替米沙坦片芯制备替米沙坦氨氯地平片,并对其溶出行为和稳定性进行评价。方法 采用流化床一步造粒工艺制备替米沙坦颗粒,用普通旋转压片机制备替米沙坦片芯,然后用氨氯地平混悬液对替米沙坦片芯进行包衣,并以溶出曲线相似性f₂值作为评价指标,通过正交设计进行处方优化,用HPLC进行含量和杂质检测,通过加速和长期试验考察片剂稳定性和溶出度。结果 制备的替米沙坦氨氯地平片质量稳定,具有与原研制剂一致的溶出特征。结论 以氨氯地平包衣替米沙坦片芯制备替米沙坦氨氯地平片具有一定的可行性。     

亲水凝胶骨架材料制备盐酸帕罗西汀缓释片的可行性研究

目的 采用亲水凝胶骨架材料制备盐酸帕罗西汀缓释片,并对其质量进行评价。方法 采用亲水凝胶骨架材料HPMC K100LV和K4M联用,通过干法制粒工艺制备盐酸帕罗西汀骨架片芯,然后通过肠溶薄膜包衣液对盐酸帕罗西汀骨架片芯进行包衣,获得盐酸帕罗西汀缓释片;以溶出曲线相似性f₂值作为评价指标,通过正交设计进行处方优化,用高效液相色谱法进行含量和杂质检测,通过加速和长期试验考察片剂稳定性。结果 以该方法制备的盐酸帕罗西汀缓释片质量稳定,具有与原研制剂一致的溶出特征。结论 该方法制备盐酸帕罗西汀缓释片具有可行性。     

近红外光谱技术测定复方丹参脉冲片衣膜厚度及其与体外释药时滞相关性的研究

摘要：目的：采用近红外漫反射光谱分析技术,建立快速、无损测定复方丹参脉冲片包衣膜厚度的方法,并进一步对衣膜厚度与体外释药时滞的相关性进行研究。方法：采集不同厚度脉冲片样品的近红外光谱,对光谱的预处理方法、建模波段、主因子数进行优选,采用偏最小二乘回归方法（PLSR）建立包衣膜厚度的近红外光谱定量校正模型,并对所建模型进行方法学考察。采用不同的方程拟合释药时滞及衣膜破裂时间与衣膜厚度的相关关系。结果：所建包衣膜厚度的近红外光谱定量校正模型相关系数r为0.992 7,内部交叉验证均方根误差（RMSECV）为3.35μm,预测均方根误差（RMSEP）为4.15μm。释药时滞及衣膜破裂时间与衣膜厚度的相关性以二项式拟合效果最优。结论：本试验所建中药脉冲片包衣膜厚度测定方法快速、无损、可靠,可进一步应用于评价及指导脉冲制剂的体内外释药行为研究和中药生产包衣过程的在线检测。     

近红外光谱法鉴别普伐他汀钠片及其原料药晶型的一致性研究

目的 建立全覆盖抽样的普伐他汀钠片的近红外光谱法一致性检验模型,考察制剂工艺的差别和原料药晶型的差异,通过稳健、准确、代表性强的近红外光谱一致性模型实现普伐他汀钠片的快速检验和筛查。方法 对评价性抽验抽取的5个企业中的4个共65批样品建立普伐他汀钠片近红外一致性检验模型,并对4个厂家的原料药的近红外光谱图进行比较。结果 建立了4个厂家普伐他汀钠片剂的近红外一致性模型,预测成功率均为100%;4种原料药和1种无定型粉末的近红外光谱图显示不同晶型光谱图具有差异。结论 近红外光谱法能够用于快速鉴别质量工艺稳定的普伐他汀钠片产品,对制剂工艺进行考察,并能够区分不同晶型的原料药。     

薄膜包衣技术在制剂生产中的应用

包衣是指在粒芯的外表包裹一层物质，粒芯可以是粉末、颗粒、小丸或片子。包衣有多种目的，如可以防潮、防机械力、掩味、上色或改进药物活性成分的释放性能等。包衣工艺主要有糖衣包衣工艺和薄膜包衣工艺两种。糖衣包衣工艺主要是将糖浆、滑石粉、色素喷射到片芯表面形成衣层；薄膜包衣工艺则是喷射聚合物溶液或混悬液到片芯表面形成衣层。糖衣包衣工艺是较古老的制药工艺，薄膜包衣工艺属于后起之秀，现在已经得到了广泛的研究，不同的配方和潜在的用途正在得到人们充分的认识，已引起制药工业的重视并迅速推广。一、薄膜包衣工艺原理薄膜…     

盐酸小檗碱肠溶缓释片制剂工艺研究

目的 研究盐酸小檗碱肠溶缓释片的制剂工艺。方法 采用体外释放度评价的方法,以单因素设计及正交设计筛选片芯处方及工艺,并对片芯进行肠溶包衣,制备盐酸小檗碱肠溶缓释片。结果 体外释放度实验显示,片芯及肠溶片均符合Higuchi释药模型。结论 盐酸小檗碱肠溶缓释片工艺稳定,体外释放符合设计要求。     

兰索拉唑肠溶微丸型口崩片的制备研究

摘 要 目的：制备兰索拉唑肠溶微丸并压制成口崩片,评价耐酸性和释放度。方法: 采用流化床包衣法制备兰索拉唑肠溶微丸,考察了丙烯酸树脂L30D 55和丙烯酸树脂NE30D配比、增塑剂用量和压片主压力对兰索拉唑肠溶微丸型口崩片的耐酸性和释放度的影响,并采用f2相似因子法评价了自制兰索拉唑肠溶微丸型口崩片与市售制剂的体外释放相似性。结果:选用微晶纤维素丸芯平均粒径为150~180 μm载药,隔离层增重为10%,丙烯酸树脂L30D 55和丙烯酸树脂NE30D配比为8∶〖KG-*2〗2,肠溶衣包衣增重为30%,增塑剂用量为20%,压片主压力为10~16 kN,制备的兰索拉唑肠溶微丸在压片过程中肠溶衣膜未发生破裂,表现出良好的耐酸性,与市售制剂的体外释放度相比f2相似因子值大于50,说明两种制剂体外释放行为相似。结论:本研究制备的兰索拉唑肠溶微丸型口崩片的耐酸性较好,与市售制剂相比体外释放相似性较高,可进一步放大生产。     

中药制剂防潮技术研究进展

目的 综述近年来中药制剂防潮的策略,为质量控制提供依据。 方法 通过查阅近年来国内外相关文献,进行归纳、分析和总结。 结果 中药的提取技术、辅料的选用及薄膜包衣影响中药制剂的吸湿性。 结论 中药防潮技术的研究尚需进一步地深入。     

红花注射液表面增强拉曼光谱研究

摘 要 目的： 研究红花的表面增强拉曼光谱,利用表面增强拉曼光谱技术对红花注射液进行快速有效的鉴别。 方法: 通过对红花注射液图谱与相应对照药材标准图谱的比较分析,实现对红花注射液的快速鉴别。结果:研究表明,红花的几个特征峰在表面增强拉曼光谱中得到了很明显的增强,表面增强拉曼光谱可很好地识别红花注射液。结论: 该方法简单、快速、可靠、专属性强,可以作为鉴别红花及红花注射液的方法。     

Near-Infrared Spectroscopic Monitoring of the Film Coating Process

Purpose. The purpose of this study was to investigate the potential of near-infrared (near-IR) spectroscopy for non-destructive at-line determination of the amount of polymer coat applied to tablet cores in a Wurster column. Methods. The effects of coating composition on the near-IR spectroscopic determination of ethylcellulose (Aquacoat ECD-30) or hydroxypropylmethylcellulose (HPMC)-based (Spectrablend) coating were evaluated, as were the performance of several chemometric techniques. Results. Tablets were coated with up to 30% ethylcellulose or 22% HPMC, and samples were pulled at regular intervals during each coating run. Near-IR reflectance spectra of the intact tablets were then collected. The spectra were preprocessed by multiplicative scatter correction (MSC) or second derivative (D2) calculations, and calibrations developed using either principal components (PCs) or multiple spectral wavelengths. The near-IR method provided predictions of film applied with standard errors of 1.07% w/w or less. Conclusions. Near-IR spectroscopy can be profitably employed in a rapid and non-destructive determination of the amount of polymer film applied to tablets, and offers a simple means to monitor the film coating process.     

Evaluating the effect of coating equipment on tablet film quality using terahertz pulsed imaging

In this study, terahertz pulsed imaging (TPI) was employed to investigate the effect of the coating equipment (fluid bed and drum coater) on the structure of the applied film coating and subsequent dissolution behaviour. Six tablets from every batch coated with the same delayed release coating formulation under recommended process conditions (provided by the coating polymer supplier) were mapped individually to evaluate the effect of coating device on critical coating characteristics (coating thickness, surface morphology and density). Although the traditional coating quality parameter (weight gain) indicated no differences between both batches, TPI analysis revealed a lower mean coating thickness (CT) for tablets coated in the drum coater compared to fluid bed coated tablets (p < 0.05). Moreover, drum coated tablets showed a more pronounced CT variation between the two sides and the centre band of the biconvex tablets, with the CT around the centre band being 22.5% thinner than the top and bottom sides for the drum coated tablets and 12.5% thinner for fluid bed coated tablets. The TPI analysis suggested a denser coating for the drum coated tablets. Dissolution testing confirmed that the film coating density was the drug release governing factor, with faster drug release for tablets coated in the fluid bed coater (98 ± 4% after 6 h) compared to drum coated tablets (72 ± 6% after 6 h). Overall, TPI investigation revealed substantial differences in the applied film coating quality between tablets coated in the two coaters, which in turn correlated with the subsequent dissolution performance.     

全水型薄膜包衣预混剂在复方丹参片生产中的应用研究

目的研究全水型薄膜包衣技术在复方丹参片生产中的应用,提高复方丹参片的质量稳定性。方法进行加速试验,比较复方丹参片全水型薄膜衣片与醇溶性薄膜衣片的综合质量和稳定性。结果全水型薄膜包衣片外观明显优于醇溶性薄膜衣片,在稳定性考察过程中含量测定和崩解时限均无明显变化。结论全水型薄膜包衣预混剂可用于复方丹参片的包衣生产。     

Quality by design, part III: study of curing process of sustained release coated products using NIR spectroscopy

This study investigated the potential of near infrared spectroscopy (NIRS) to assess film coat curing for tablets coated with methacrylate copolymers. The ability of NIRS to monitor film coat curing was studied and compared to conventional methods like differential scanning calorimetry (DSC) and hot-stage microscopy (HSOM). This study showed that variation in the curing temperature and duration affected the NIR spectra for all formulations. These results and the DSC and HSOM results showed that the spectral changes are due to polymer curing. In addition, glass beads, theophylline and orbifloxacin tablets were coated using Eudragit RL, RS, and L 30-D with varying ratios. Principal component analysis (PCA) was performed on the NIR spectra to investigate the effect of curing time and temperature on cast films, uncoated tablets, coated tablets and coated glass beads. Score plots showed that curing duration and temperature affected coated glass beads, uncoated and coated tablets significantly. The amount of drug released at 250 min, and the NIR spectra of cured tablets were used to develop and validate a 7-factor partial least square (PLS) regression calibration for theophylline tablets coated with Eudragit RL:RS 30-D (1:4). This study demonstrated the potential of NIRS in film coat curing and release monitoring.     

消旋山莨菪碱非铝塑包装片剂近红外鉴别模型的初探

目的采用近红外漫反射光谱分析技术和模式识别技术建立消旋山莨菪碱非铝塑包装片剂定性分析模型用于该品种的鉴别。方法以8个生产厂家的消旋山莨菪碱为分析对象,采集近红外漫反射光谱,通过导数化和矢量归一化进行预处理,应用欧氏距离方法建立消旋山莨菪碱近红外鉴别数学模型。结果消旋山莨菪碱的定性分析模型的条件参数为：谱段为5 400-7 000 cm-1,光谱预处理方法为＂一阶导数法＋归一化＂,模型的阈值为0.603。并对模型进行了验证,能满足应用的要求。结论试验结果表明应用近红外光谱技术建立消旋山莨菪碱的定性分析模型是可行的,同时为模型更新提供了一个参考的方法。     

基于近红外光谱的阿立哌唑片溶出行为研究

目的 建立阿立哌唑片剂溶出行为近红外定量模型,预测片剂的溶出行为。方法 采集阿立哌唑片剂近红外光谱,进行溶出度试验,分别于3、6、9、12、15、30 min时测定每片的溶出度,采取卷积平滑方法预处理波段4 000.00～4 396.90 cm^-1和5 326.43～12 000.00 cm^-1的近红外光谱,以偏最小二乘法建立溶出行为模型。结果 不同时间点的校正均方根误差(RMSEC)和预测均方根误差(RMSEP)均在8%以下,不同时间点校正相关系数(R_C)和预测相关系数(R_P)均在0.95以上(6 min的相关系数除外),近红外光谱和各时间点溶出度之间呈现出良好的相关性。结论 近红外光谱分析技术能够预测阿立哌唑片剂的溶出行为,为近红外光谱分析技术在线监测片剂质量奠定了理论基础。     

Determination of Tablet Coating Distribution by Deconvolution of Uncoated and Coated Tablet Weight Distributions

Purpose. The purpose of this research is to obtain the tablet coating distribution from weight distributions of uncoated and coated tablets. Methods. The method of deconvolution with digital smoothing was used to calculate the distribution of coating applied to a tablet population from separate random measurements of individual uncoated and coated tablets. Results. It was demonstrated that the calculated coating weight distribution agrees well with the measured distribution. The effect of the smoothing factor on the solution is illustrated. Conclusions. This method can be used during development to facilitate process scale-up/optimization. In routine production, the method can assess the reproducibility and consistency of a coating process.     

洛索洛芬钠片的质量分析

目的 对2017年浙江省药品生产及流通领域的41批次洛索洛芬钠片的质量进行考察分析,评价本品的质量现状并分析存在的问题。方法 将法定检验与探索性研究相结合,针对现行质量标准不完善等问题,采用X-射线衍射法考察晶型;采用HPLC进行手性分离,考察有关物质、溶出度及稳定性;采用电感耦合等离子体发射光谱仪考察溴残留;采用近红外光谱扫描法建立近红外光谱库。对法定检验及探索性研究的结果进行统计分析。结果 法定检验与探索性研究结果之间存在差异。结论 探索性研究结果表明部分法定质量标准不完善,且各厂家的产品质量有差异,应引导企业进行制剂工艺改进,提高质量,并采用更完善的方法全面控制产品质量。     

基于GA-BP人工神经网络的红霉素肠溶片效价预测研究

目的 建立一种基于GA-BP人工神经网络模型,根据组分含量数据对红霉素肠溶片效价进行预测。方法 测定552个批次红霉素肠溶片的红霉素组分A、红霉素组分B、红霉素组分C、杂质A-F和总杂质的百分含量及效价,构建GA-BP 人工神经网络模型,预测红霉素肠溶片的效价。结果 预测效价误差百分率最高值为-4.61%,均未超过5%,误差百分率平均值为2.22%,优于一般仪器分析相对标准偏差2.50%。结论 GA-BP人工神经网络对红霉素肠溶片效价预测具有较高的精度,稳定性也较好,可以用于红霉素的质量控制。