| الوصف: |
Proteins are the building blocks of life and serve a wide range of essential functions in organisms. Many metabolic reactions in organisms are catalysed by enzymes, DNA is replicated by proteins and in cells proteins often facilitate active transport of e.g. glucose or ions. Proteins also serve an essential functionality in foods, pharmaceutics, bioplastics and even clothing. Recently, the use of proteins towards higher concentrations is of interest for food, pharmaceutical and medical applications. Nevertheless, the preparation of products with desired product properties can be challenging, when approaching higher protein concentrations. Therefore, in this thesis we investigate proteins at higher concentrations, especially focussing on their drying and hydration behaviour. In part one of the thesis, the focus is on the dynamics of drying of proteins towards higher concentrations. Dense proteins systems have been scarcely studied compared to proteins at lower concentrations. We address drying behaviour where we focus on the use of whey protein isolate as a model system. In part two of the thesis we focus on the hydration properties of the corn protein zein, where we apply it as a drug excipient. In this part we also investigate the influence of hydration on the release behaviour of drugs into the hydration media. The drying part (part one) contains two studies. The first study is more fundamental in nature, focussing on the drying of a protein coating. In previous studies mainly the macroscopic properties of protein coatings after drying are investigated, leaving the drying dynamics virtually unexplored. Here we investigate the drying behaviour of the model protein β-lactoglobulin on multiple length scales with an unique combination of in-line techniques. On the microscopic length scale we use dynamic vapour sorption and magnetic resonance imaging while on a smaller length scales, we apply diffusing wave spectroscopy and IR-spectroscopy to monitor the drying process. For all used techniques, the changes in the measured physical properties of the coating as a function of water weight fraction Xw from Xw = 0.8 down to Xw = 0.2 are gradual. However, using dynamic vapour sorption and IR-spectroscopy we measure a sharp change below water weight fractions of Xw = 0.2. We hypothesise that changes in the molecular interactions caused by dehydration of the protein results in a change in the drying kinetics of the film. In the second study of part one, protein drying is approached on a more applied level, where we study the drying of a spherical droplet. We use single droplet drying as a methods that can model the spray drying process in a simplified and well-controlled way. Sessile droplets are subjected to varying drying conditions such as temperature, initial protein concentration, presence of airflow and droplet rotation. During these experiments the morphological development is monitored by a camera. After drying, scanning electron microscopy and X-ray tomography are used to examine the particles that are formed after complete drying. Irrespective of the conditions used, we observe an initial droplet shrinkage, followed by the nucleation of a hole in the droplet skin, which is followed by the formation of a vacuole. The drying conditions used, strongly influenced the location of the hole and the locking point prior to hole formation. We hypothesise that the location of the hole is caused by local inhomogeneities in protein concentration causing a the nucleation of the hole where the local skin modulus is lowest. Also the locking point of the droplet is found to be due to a inhomogeneity over the whole droplet caused by rapid evaporation. These results can be of importance to understand powder structure and functionality as obtained in spray drying. In the hydration part (part 2), we investigate the potential of zein as a sole excipient in macroscale caplets obtained by hot melt extrusion (HME) and injection moulding (IM). Zein is good candidate as a sustained release agent, because it is insoluble in two studies. In the first study zein matrices were loaded with the drug paracetamol. Physical mixtures of zein, water and crystalline paracetamol are extruded and injection moulded into caplets. Characterisation of these caplets is performed using differential scanning calorimetry, IR- spectroscopy, scanning electron microscopy and powder X-ray diffraction. The hydration and drug release kinetics from the caplet slices is measured. We find that the drug release kinetics is broadly independent of the dissolution medium and drug loading. The release kinetics is diffusion limited and could be well described by a 2D diffusion model. The results demonstrate that the drug release rate from zein caplet slices can be tuned by its dimensions. In the second study, a wider range of drugs differing in hydrophobicity is studied. Next to paracetamol, we have used two other model drugs: the hydrophobic indomethacin and the more hydrophilic ranitidine. The zein matrix is capable to stabilize the different dugs in a non-crystalline state, which is promising especially for increasing the bioavailability of poorly water-soluble drugs. Overall crystallinity of the drugs in the caplets increases with its degree of hydrophobicity. For the poorly soluble indomethacin, dissolution rates at low pH were higher from caplet slices, compared to the dissolution rates of indomethacin crystals by themselves. In addition, we found that the electrostatic interactions between zein and drugs can also be used to influence the release kinetics. Various aspects were found to be of importance both for drying and hydration of concentrated protein systems. The homogeneity during both processes deserves attention as its manipulation can strongly influence final properties if the system. Also the plasticising effect of water on dense proteins is often found essential, when understanding the dynamics of both drying and hydration processes. Finally protein hydrophobicity and its manipulation can provide a window of opportunities in many applications which are involve by drying or hydration. |
