Automated Extrusion-Based Dispensing: Personalized Dosing and Quality Control of Clopidogrel Tablets for Pediatric Care.

Abstract

The exploration of three-dimensional (3D) printing inspired technologies in pharmaceutical compounding reveals a promising frontier in personalized medicine manufacture. This study focuses on the development of clopidogrel bisulphate tablets, with doses ranging from 2 mg to 20 mg per tablet, suitable for pediatric use. The study explored a semi-solid extrusion-based deposition technology already being used in compounding pharmacies across several European locations. The investigation explored various properties of two formulations of 1% and 2% clopidogrel gel tablets, with a specific focus on mass variation, drug content uniformity, in vitro drug release profiles, disintegration time, and stability. The mean weights of the smallest printed 200 mg tablets with 1% and 2% clopidogrel concentrations were 199.1 ± 4.6 mg and 201.0 ± 3.2 mg, respectively. For the largest printed 500 mg tablets with 1% and 2% concentrations, the mean weights were 499.3 ± 7.7 mg and 501.7 ± 6.5 mg, respectively. The mean clopidogrel content uniformity for 1% clopidogrel 200 mg and 500 mg tablets were 102.0 ± 1.8%and 96.6 ± 2.6%, respectively, and for 2% clopidogrel 200 mg and 500 mg were 102.6 ± 3.9% and 101.2 ± 1.6%, respectively, well within the acceptable acceptance value (AV) range of 3 to 12. Both 1% and 2% formulations of clopidogrel tablets exhibited rapid drug release, meeting the USP pharmacopeial target of 85% release in 15 minutes. All tablet sizes formulated at 1% and 2% concentrations met specified disintegration specifications. The stability assessment over three months revealed consistent pH values and assay results within target specifications for both clopidogrel formulations (93.5% for 1% formulation and 93.6% for 2% formulation). At three months, X-ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) results demonstrated stability in clopidogrel tablets. In conclusion, a comprehensive evaluation of our developed clopidogrel tablets demonstrate their suitability for clinical use in an extemporaneous setting using the presented semi-solid extrusion-based automation technology.