Benchmarking pharmaceutical quality and manufacturing costs of 3D printing against conventional compounding methods for personalization of medicine

Abstract

Background: Modification of commercially available medicine, e.g. splitting or dissolving of tablets or pharmacy compounding, is current clinical practice when desired oral dosage forms are unavailable. These practices are defined as conventional pharmacy compounding techniques and are used to produce medicines that are not commercially available. 3D printing is an automated compounding technique that allows pharmacists to personalize oral dosage forms. This study aimed to compare the quality of 3D printing hydrocortisone tablets with conventional pharmacy compounded formulations. Secondary and tertiary aims were to assess manufacturing costs of 3D printed tablets and to explore whether modifying the hydrocortisone drug release profile is possible using 3D printing.

Methods: Semi-solid extrusion (SSE) 3D printing was used to produce immediate release and sustained release hydrocortisone tablets. Conventional compounded hydrocortisone formulations were used as comparators, including pharmacy compounded capsules, split tablets, and commercially available tablets dissolved in syringes.

Results: Immediate and sustained release hydrocortisone tablets were printed successfully. The acceptance values (AVs) of 3D printed tablets, tablet dissolved-in-syringe and one batch of pharmacy compounded capsules were ≤ 15. The AVs of the other 2 pharmacy compounded capsules and split tablets were > 15 and did not comply with content uniformity requirements. Personalization of 3D printed tablets was possible with a dose range of 0.5 - 10.0 mg. Costs of 3D printed tablets were <€ 3.00 per tablet for both release profiles.

Conclusion: SSE 3D printing leads to higher quality hydrocortisone tablets compared to conventional pharmacy compounding methods at acceptable manufacturing costs. 3D printing further allows for modification of hydrocortisone release profiles, which is not possible using conventional manufacturing methods. The low dose minitablets are especially suitable for pediatric indications requiring a personalized hydrocortisone dose.

Keywords: 3d printing; Cost of pharmaceutical 3d printing; Hydrocortisone; Personalized medicine; Pharmaceutical technology; Quality of pharmaceutical 3d printing; compounding.