A new chapter in pharmaceutical manufacturing: 3D-printed drug products.

FDA recently approved a 3D-printed drug product in August 2015, which is indicative of a new chapter for pharmaceutical manufacturing. This review article summarizes progress with 3D printed drug products and discusses process development for solid oral dosage forms. 3D printing is a layer-by-layer process capable of producing 3D drug products from digital designs. Traditional pharmaceutical processes, such as tablet compression, have been used for decades with established regulatory pathways. These processes are well understood, but antiquated in terms of process capability and manufacturing flexibility. 3D printing, as a platform technology, has competitive advantages for complex products, personalized products, and products made on-demand. These advantages create opportunities for improving the safety, efficacy, and accessibility of medicines. Although 3D printing differs from traditional manufacturing processes for solid oral dosage forms, risk-based process development is feasible. This review highlights how product and process understanding can facilitate the development of a control strategy for different 3D printing methods. Overall, the authors believe that the recent approval of a 3D printed drug product will stimulate continual innovation in pharmaceutical manufacturing technology. FDA encourages the development of advanced manufacturing technologies, including 3D-printing, using science- and risk-based approaches.

Additively manufactured medical products - the FDA perspective.

Additive manufacturing/3D printing of medical devices is becoming more commonplace, a 3D printed drug is now commercially available, and bioprinting is poised to transition from laboratory to market. Despite the variety of technologies enabling these products, the US Food and Drug Administration (FDA) is charged with protecting and promoting the public health by ensuring these products are safe and effective. To that end, we are presenting the FDA's current perspective on additive manufacturing/3D printing of medical products ranging from those regulated by the Center for Devices and Radiological Health (CDRH), the Center for Drug Evaluation and Research (CDER), and the Center for Biologics Evaluation and Research (CBER). Each Center presents an overview of the additively manufactured products in their area and the specific concerns and thoughts on using this technology in those product spaces.

An improved method for the characterization of supersaturation and precipitation of poorly soluble drugs using pulsatile microdialysis (PMD).

In current pharmaceutical drug discovery, most candidates are poorly soluble in water, which can result in poor bioavailability. To overcome this problem, formulations that create supersaturation of the drug are a well-studied alternative. Characterizing the dissolution from these systems is challenging because conventional methods, such as sampling with a syringe then filtering with a 0.2-0.45 µm filter before an HPLC assay, can overestimate the concentration of dissolved drug by allowing nuclei or small precipitated particles to pass, which then dissolve in the HPLC mobile phase. Nuclei and small particles can also cause overestimation of the dissolved concentration when using optical methods. Such overestimations can lead to failure of in vivo prediction of drug bioavailability from supersaturated systems. This paper reports a novel method to determine the free dissolved drug concentration in a dissolution medium using pulsatile microdialysis (PMD). Ibuprofen was used as a model drug for determining precipitation and supersaturation. Supersaturation was induced chemically by changing pH, and also by dissolution/release from an in-house formulation. The adaptation of a previously developed PMD model is summarized, and experimental results comparing dissolved concentrations determined using PMD and direct sampling by syringe and filtering are presented.