3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics
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- 作者：Alvaro Goyanes ; Jie Wang ; Asma Buanz ; Ram贸n Mart铆nez-Pacheco ; Richard Telford ; Simon Gaisford ; Abdul W. Basit
- 刊名：Molecular Pharmaceutics
- 出版年：2015
- 出版时间：November 2, 2015
- 年：2015
- 卷：12
- 期：11
- 页码：4077-4084
- 全文大小：447K
- ISSN：1543-8392
文摘
Three dimensional printing (3D printing) was used to fabricate novel oral drug delivery devices with specialized design configurations. Each device was loaded with multiple actives, with the intent of applying this process to the production of personalized medicines tailored at the point of dispensing or use. A filament extruder was used to obtain drug-loaded鈥攑aracetamol (acetaminophen) or caffeine鈥攆ilaments of poly(vinyl alcohol) with characteristics suitable for use in fused-deposition modeling 3D printing. A multinozzle 3D printer enabled fabrication of capsule-shaped solid devices containing the drug with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different to the drug in the adjacent layers, and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least-squares component matching to produce false color representations of distribution of the drugs was used. This clearly showed a definitive separation between the drug layers of paracetamol and caffeine. Drug release tests in biorelevant bicarbonate media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both paracetamol and caffeine was simultaneous and independent of drug solubility. With the DuoCaplet design, it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device; the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design configurations and unique drug release characteristics, which would not otherwise be possible using conventional manufacturing methods.