Computer numerical control (CNC) carving as an on-demand point-of-care manufacturing of solid dosage form: A digital alternative method for 3D printing

Abstract

Computer numerical control (CNC) carving is a widely used method of industrial subtractive manufacturing of wood, plastics, and metal products. However, there have been no previous reports of applying this approach to manufacture medicines. In this work, the novel method of tablet production using CNC carving is introduced for the first time. This report provides a proof-of-concept for applying subtractive manufacturing as an alternative to formative (powder compression) and additive (3D printing) manufacturing for the on-demand production of solid dosage forms. This exemplar manufacturing approach was employed to produce patient-specific hydrocortisone (HC) tablets for the treatment of children with congenital adrenal hyperplasia. A specially made drug-polymer cast based on polyethene glycol (PEG 6,000) and hydroxypropyl cellulose was produced using thermal casting. The cast was used as a workpiece and digitally carved using a small-scale 3-dimensional (3D) CNC carving. To establish the ability of this new approach to provide an accurate dose of HC, four different sizes of CNC carved tablet were manufactured to achieve HC doses of 2.5, 5, 7.5 and 10 mg with a relative standard deviation of the tablet weight in the range of 3.69-4.79%. In addition, batches of 2.5 and 5 mg HC tablets met the British Pharmacopeia standards for weight uniformity. Thermal analysis and X-ray powder diffraction indicated that the model drug was in amorphous form. In addition, HPLC analysis indicated a level of purity of 96.5 ± 1.1% of HC. In addition, the process yielded mechanically strong cylindrical tablets with tensile strength ranging from 0.49 to 1.6 MPa and friability values of <1%, whilst maintaining an aesthetic look. In vitro, HC release from the CNC-carved tablets was slower with larger tablet sizes and higher binder contents. This is the first report on applying CNC carving in the pharmaceutical context of producing solid dosage forms. The work showed the potential of this technology as an alternative method for the on-demand manufacturing of patient-specific dosage forms.

Keywords: CNC milling; Patient-specific; Personalized dosage form; Subtracting manufacturing.