The Development of Direct Extrusion-Injection Moulded Zein Matrices as Novel Oral Controlled Drug Delivery Systems
- 467 Downloads
To evaluate the potential of zein as a sole excipient for controlled release formulations prepared by hot melt extrusion.
Physical mixtures of zein, water and crystalline paracetamol were hot melt extruded (HME) at 80°C and injection moulded (IM) into caplet forms. HME-IM Caplets were characterised using differential scanning calorimetry, ATR-FTIR spectroscopy, scanning electron microscopy and powder X-ray diffraction. Hydration and drug release kinetics of the caplets were investigated and fitted to a diffusion model.
For the formulations with lower drug loadings, the drug was found to be in the non-crystalline state, while for the ones with higher drug loadings paracetamol is mostly crystalline. Release was found to be largely independent of drug loading but strongly dependent upon device dimensions, and predominately governed by a Fickian diffusion mechanism, while the hydration kinetics shows the features of Case II diffusion.
In this study a prototype controlled release caplet formulation using zein as the sole excipient was successfully prepared using direct HME-IM processing. The results demonstrated the unique advantage of the hot melt extruded zein formulations on the tuneability of drug release rate by alternating the device dimensions.
KEY WORDScontrolled release diffusion mechanism dissolution kinetics modelling hot melt extrusion-injection moulding Zein
Attenuated Total Reflection Fourier Transform Infrared Spectroscopy
Differential Scanning Calorimetry
Hot melt extrusion
Hot melt extrusion-injection moulding
Powder X-ray diffraction
Scanning electron microscopy
Glass transition temperature
ACKNOWLEDGMENTS AND DISCLOSURES
This work is part of the Industrial Partnership Programme (IPP) Bio(-Related)Materials of the Stichting voor Fundamenteel Onderzoek der Materie (FOM), which is financially supported by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO). The IPP BRM is co-financed by the Top Institute Food and Nutrition and the Dutch Polymer Institute.
- 23.Gopalakrishnan TR. Polymorphism of acetaminophen under nanoconfinement, Naturwissenschaftliche Fakultät II, Martin-Luther-Universität Halle-Wittenberg, Halle, 2010.Google Scholar