The applicability of pharmaceutical polymeric blends for the fused deposition modelling (FDM) 3D technique: Material considerations-printability-process modulation, with consecutive effects on in vitro release, stability and degradation
The applicability of pharmaceutical polymeric blends for the fused deposition modelling (FDM) 3D technique: Material considerations-printability-process modulation, with consecutive effects on in vitro release, stability and degradation
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DOI：
10.1016/j.ejps.2018.12.019
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发表时间：
2019-03-01
影响因子：
4.6
通讯作者：
Nagy, Zsombor Kristof
中科院分区：
文献类型：
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作者：
Ilyes, Kinga;Kovacs, Norbert Krisztian;Nagy, Zsombor Kristof
与传统的生产方法相比，制药领域的三维打印(3DP)构成了一种替代的、创新的方法。熔融沉积建模是一种简单、经济的3DP技术，但可应用于该方法的药物辅料的范围受到限制。这项研究旨在使用定制的药用聚合物长丝作为技术支持，确定FDM印刷适性的要求，并评估这些新剂型是否符合当前的GMP/GCP质量标准。根据仪器的功能对配方原理进行了评估。根据API(卡维地洛)热重分析确定的临界限值对共混物的加工性进行了预筛选。该工艺过程意味着使用FDM和热熔融挤压(HME)，而印刷适宜性是通过热、流变和机械测量来确定的。从制药的角度来看，体外溶出动力学的一致性是在释放时和稳定时进行监测的，而印刷工艺的影响则是基于先前确定的加工潜力进行评估的。结果表明，熔体的印刷适性是多因素的，脆性和熔体粘度是主要的限制因素。剪切变稀和弯曲模数的增加可以使可加工性区间更宽，这反过来被证明是限制降解产物形成的关键。3DP片剂对原料药的释放率较高，但生产和储存过程中的温湿度可能会影响最终产品的质量，应慎重考虑。总之，HME+FDM可以被认为是一种替代的生产方法，在临床部门具有应用前景，但对于某些制剂，在确认其适用性之前，需要进行广泛的包装开发。
The three dimensional printing (3DP) in the pharmaceutical domain constitutes an alternative, innovative approach compared to the conventional production methods. Fused deposition modelling (FDM), is a simple, cost-effective 3DP technique, however the range of pharmaceutical excipients that can be applied for this methodology is restricted. The study set to define the requirements of the FDM printability, using as technical support custom made, pharmaceutical polymer based filaments and to evaluate if these new dosage forms can live up to the current GMP/GCP quality standards. Formulation rationale was assessed in accordance to the apparatus functionality. Blends were pre-screened based on the processability under the API (carvedilol) thermogravimetric analysis determined critical limit. The technological process implied the use of FDM coupled with hot melt extrusion (HME), while printability was defined by means of thermal, rheological and mechanical measurements. From the pharmaceutical standpoint, the consistency of the in vitro dissolution kinetics was monitored 'at release' and 'in stability', while the print process impact was evaluated based on the previously determined processability potential. Results showed that FDM printability is multifactorial, with brittleness and melt viscosity as primary limitation factors. The increase in shear-thinning and flexural modulus can enable broader processability intervals, which in turn proved to be essential in limiting degradation product formation. The 3DP tablets released the API in an extended rate, however the temperature and humidity along production and storage should be carefully considered as it may affect the final product quality in time. In conclusion, HME + FDM can be considered as an alternative production methodology, with prospects of applicability in the clinical sector, however for some formulations extensive packaging development will be necessary before confirming their suitability.