UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Automated therapy preparation of isoleucine formulations using 3D printing for the treatment of MSUD: first single-centre, prospective, crossover study in patients

Goyanes, A; Madla, CM; Umerji, A; Piñeiro, GD; Montero, JMG; Diaz, MJL; Barcia, MG; ... Basit, AW; + view all (2019) Automated therapy preparation of isoleucine formulations using 3D printing for the treatment of MSUD: first single-centre, prospective, crossover study in patients. International Journal of Pharmaceutics , 567 , Article 118497. 10.1016/j.ijpharm.2019.118497. Green open access

[thumbnail of Gaisford_Automated therapy preparation of isoleucine formulations using 3D printing for the treatment of MSUD_AAM.pdf]
Preview
Text
Gaisford_Automated therapy preparation of isoleucine formulations using 3D printing for the treatment of MSUD_AAM.pdf - Accepted Version

Download (930kB) | Preview

Abstract

Maple syrup urine disease (MSUD) is a rare metabolic disorder with a worldwide prevalence of 1 in every 185,000 live births. However, certain populations display a significant overexpression of the disorder where incidence is reported to be 1 in every 52, 541 new-borns. The first-line therapy for MSUD involves a strict dietary leucine restriction and oral supplementation of isoleucine and valine. The dose administered to patients requires strict tailoring according to age, weight and blood levels. In current clinical practice, however, practitioners still have to prepare extemporaneous formulations due to the lack of suitable oral treatments for MSUD. Herein we evaluate for the first time the use of 3D printing in a hospital setting for the preparation of personalised therapies with the aim of improving safety and acceptability to isoleucine supplementation in paediatric patients suffering from MSUD. The study was a single-centre, prospective crossover experimental study. Four paediatric patients with MSUD (aged 3-16 years) were treated at the Clinic University Hospital in Santiago de Compostela, Spain which is a MSUD reference hospital in Europe. The primary investigation was to evaluate isoleucine blood levels after six months treatment with two types of formulations; conventional capsule prepared by manual compounding and personalised chewable formulations prepared by automated 3D printing. A secondary investigation was to evaluate patient acceptability of 3D printed formulations prepared with different flavours and colours. Isoleucine blood levels in the patients were well controlled using both types of formulations, however, the 3D printed therapy showed mean levels closer to the target value and with less variability (200 - 400µM). The 3D printed formulations were well accepted by the patients regarding flavour and colour. The study demonstrates for the first time that 3D printing offers a feasible, rapid and automated approach to prepare oral tailored-dose therapies in a hospital setting. 3D printing has shown to be an effective manufacturing technology in producing chewable isoleucine printlets as a treatment of MSUD with good acceptability.

Type: Article
Title: Automated therapy preparation of isoleucine formulations using 3D printing for the treatment of MSUD: first single-centre, prospective, crossover study in patients
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ijpharm.2019.118497
Publisher version: https://doi.org/10.1016/j.ijpharm.2019.118497
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: 3D printed drug products, Three dimensional printing, drug compounding, maple syrup urine disease, pediatric pharmacy, personalized medicine
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/10078165
Downloads since deposit
375Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item