Development and design of double-layer co-injection moulded soy protein based drug delivery devices Cla ´udia M. Vaz a,1 , P.F.N.M. van Doeveren b , R.L. Reis a,c , A.M. Cunha a, * a Department of Polymer Engineering, University of Minho, Campus de Azure ´m, 4800-058 Guimara ˜es, Portugal b ATO B.V., Institute of Agrotechnological Research, P.O. Box 17, 6700 AA Wageningen, The Netherlands c 3B’s Research Group-Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Portugal, Campus de Gualtar, 4710-057 Braga, Portugal Received 13 February 2003; received in revised form 28 April 2003; accepted 28 April 2003 Dedicated to Prof. Ian M. Ward on the occasion of his 75th birthday Abstract Novel double-layer delivery devices based on soy protein derived materials were designed and produced using an innovative two material co-injection moulding technique. It was demonstrated that the viscosity ratio between core and skin layer materials played an important role in the formation of the interfacial shape, namely the skin thickness and uniformity of the bi-materials. The adequate selection of the materials used and the optimisation of the respective processing conditions enabled an accurate control of the relative thickness of the layers of the device. The preliminary results confirmed the potential of these systems to achieve a controlled drug delivery. q 2003 Elsevier Ltd. All rights reserved. Keywords: Soy protein derived material; Mono-sandwich injection molding; Double-layer delivery device 1. Introduction In the past decades, numerous methodologies have been investigated in order to produce controlled-release devices presenting zero-order release kinetics over a prolonged period of time [1–4]. These systems can maintain the drug in the desired therapeutic range with just a single dose, offering a number of advantages comparatively to the conventional-release systems [5]. In terms of formulation, monolithic matrix devices (e.g. tablets, particles, etc.) are widely used due to their easy administration and low cost of manufacturing [6]. However, these systems are incapable of attaining zero-order release, exhibiting continuously diminishing delivery rates [7, 8]. The most common approach to overcome this problem and to modify such type of release profiles is the restriction of the exposed surface. This reduces the contact with the fluids and is normally achieved by the addition of barrier layers. The production of either multi-layer tablets (by partial coating or compression coating) or core-shell particles (by complex coacervation, freeze-drying, etc.) were attempted by several research groups and have been extensively investigated [9–16]. More recently, methods involving melt-based processing techniques have also been described for the preparation of this type of devices. The co-extrusion technology is a known example [17]. A less conventional approach is based on a two-material co-injection moulding technology. This tech- nique allows the simultaneous moulding of two polymers into the desired shape, without requiring further finishing operations. The immediate result is a part with high dimensional accuracy and adjustable skin-core morphology [18]. Besides the economical advantages, the process offers: (i) suitability for a large variety of polymeric matrices; (ii) opportunity for simultaneous use of polymers of different nature; (iii) precise control of the skin-core layers’ thickness by adjustment of the processing parameters; and (iv) a good interface between the two materials (if compatible matrices are used) [19–21]. Therefore, co-injection moulding may allow for the combination of a functional core material (with an encapsulated bioactive agent) with a skin layer, which will act as an effective barrier for the early drug diffusion. Since it has been shown that it is possible to produce protein 0032-3861/03/$ - see front matter q 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0032-3861(03)00549-4 Polymer 44 (2003) 5983–5992 www.elsevier.com/locate/polymer 1 Tel.: þ31-40-247-4839; fax: þ 31-40-244-7355. * Corresponding author. Tel.: þ351-253-510-399; fax: þ 351-253-510- 322. E-mail address: amcunha@dep.uminho.pt (A.M. Cunha).