Controlled release from zein matrices: Interplay of drug hydrophobicity and pH

Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods: Caplets were prepared by hot-melt extrusion (HME) and injection moulding (IM). Each of the three model drugs were tested on two drug loadings in various dissolution media. The physical state of the drug, microstructure and hydration behaviour were investigated to build up understanding for the release behaviour from zein based matrix for drug delivery. Results: Drug crystallinity of the caplets increases with drug hydrophobicity. For ranitidine and indomethacin, swelling rates, swelling capacity and release rates were pH dependent as a consequence of the presence of charged groups on the drug molecules. Both hydration rates and release rates could be approached by existing models. Conclusion: Both the drug state as pH dependant electrostatic interactions are hypothesised to influence release kinetics. Both factors can potentially be used factors influencing release kinetics release, thereby broadening the horizon for zein as a tuneable release agent

The development of direct extrusion-injection moulded zein matrices as novel oral controlled drug delivery systems

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 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. Results: 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. Conclusions: 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

A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

BACKGROUND: This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. DISCUSSION: The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. SUMMARY: Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine

Enhanced performance measurement using OR: a case study

The case study described in this paper aims to illustrate how qualitative and quantitative system dynamics modelling and multicriteria analysis can be used in an integrated way to enhance the process of performance measurement and management in the radiotherapy department of a major UK cancer treatment centre. The complexity of the radiotherapy process and its significance for patients present particular challenges for performance measurement and management. The paper discusses the benefits arising and the practical difficulties faced in the study