The Development of Direct Extrusion-Injection Moulded Zein Matrices as Novel Oral Controlled Drug Delivery Systems

Abstract

Purpose To evaluate the potential of zein as a sole excipient for controlled release formulations prepared by hot melt extrusion.Methods Physical mixtures of zein, water and crystalline paracetamol were hot melt extruded (HME) at 80ºC 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. ResultsFor the formulations with lower drug loadings, the drug was found to be in the noncrystalline 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. ConclusionsIn 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.

Swelling of Zein Matrix Tablets Benchmarked against HPMC and Ethylcellulose: Challenging the Matrix Performance by the Addition of Co-Excipients

“…The burst release observed with zein here has been documented in other studies with tablets and capsules, where zein and drug were present as physical mixtures and pores were present in the matrix [7,10]. However, in the case of hot-melted extruded caplets, characterized by a continuous and less porous matrix and by a more intimate mixing between drug and polymer, the drug burst was not observed [11,12].…”

“…It should be noted that a single medium, i.e., phosphate buffer, was used in the swelling and release studies, in order to minimize the number of confounding factors in the discussion of the influence of excipients on zein. Nevertheless, the effect of medium pH and ionic strength on zein matrices has been previously well characterized [5,7,10,11,12,13].…”

“…Possible pharmaceutical and biomedical applications of zein include its use in tissue engineering [1,2] and in the formulation of microparticles, nanoparticles, and films [3,4]. Moreover, zein has also been utilized as a matrix-forming polymer for controlled drug release in macroscopic pharmaceutical dosage forms [5], including tablets [6,7,8,9], capsules [10], and hot-melt extruded caplets [11,12].…”

Application of nanoparticles and composite materials for energy generation and storage

“…The method of preparation of composite materials has a direct effect on the overall performance of the materials. Several methods have been explored to compound polymer matrix, which includes injection moulding [7, 8], compression moulding [2, 9], extrusion moulding [10], resin transfer moulding (RTM) [11], hand lay‐up [12]. A good understanding of the processing parameters (temperature, velocity/time and pressure) will contribute to the properties of the composites.…”

Plasticized protein for 3D printing by fused deposition modeling

“…For a content of 22% glycerol (w/w), it presents a glass transition temperature, Tg, at about 60°C, and a storage modulus, E', at about 1GPa, in ambient conditions [16]. Plasticized zein, added with paracetamol, has been recently considered as extruded-molded caplets for controlling drug release [17]. Thus, this protein is a promising compound for processing as a molten thermoplastic biopolymer, in the case of Fused Deposition Modeling, to obtain tridimensional structured parts presenting a defined porosity, which could be used for the controlled release of bioactive molecules.…”