Teknisk- naturvetenskaplig fakultet UTH-enheten Besöksadress: Ångströmlaboratoriet Lägerhyddsvägen 1 Hus 4, Plan 0 Postadress: Box 536 751 21 Uppsala Telefon: 018 – 471 30 03 Telefax: 018 – 471 30 00 Hemsida: http://www.teknat.uu.se/student Abstract Beläggning av små partiklar Coating fine particles Andrea Bergqvist
Controlled release of an active is used in many applications. An example is drug delivery were it is desirable to release the active substance close to the target. In paints can anti-mold substances be encapsulated and released slowly during a long time which can extend the lifetime of the paint. This work investigated a coating process of loaded particles with as low leakage of the active substance as possible. It was also studied if the coating process was scalable. The particles in use were porous silica that was coated with sodium dodecyl sulphate (SDS), polyethyleneimine (PEI) and tetraethyl orthosilicate (TEOS). To fill particles, the active was dissolved in a solution and the particles were added. The active adsorbed into the pores of the particle. The coating principle was about the same for all layers. The coating molecules were dissolved in a solvent and the particles were added during stirring. After centrifugation the coated particles were separated from the solvent and left to dry. The thermogravimetric analyzer (TGA) was used to calculate the amount of adsorbed polymers on the particle surface. UV/VIS spectrometer analyzed the release rate of the active.
As the recipe was optimized, SDS could be excluded from the process. An adsorption isotherm for PEI on the particle surface showed that 0.5 g PEI/ g particle the ratio required for covering the surface completely. It was proved that if the active was dissolved in all coating solutions during the coating, less leakage appear and makes the coating process more controlled. A higher amount of both PEI and TEOS improves the encapsulation of the active, which reduces the release rate. The coating process is proved to be scalable as the particle concentration is increased from 4.72 % to 16.5 % without too much agglomeration.
ISSN: 1650-8297, UPTEC K14009 Examinator: Mats Boman Ämnesgranskare: Karin Larsson Handledare: Anders Larsson
Svensk sammanfattning
Summary in Swedish
Kontrollerad frisättning av ett aktivt ämne är vanligt förkommande i många
applikationer. Några exempel är inkapsling av läkemedel för transport i kroppen där frisättningen ska ske så nära ”målet” som möjligt. I målarfärg kapslas anti-‐mögelmedel in för att läcka ut långsamt och motverka mögelväxt under en längre tid.
Detta examensarbete är en granskning av en beläggningsprocess av fyllda partiklar. Beläggningen ska göras med så lågt läckage av det aktiva ämnet som möjligt.
Beläggningsprocessen optimerades och slutligen undersöktes om den var skalbar. Porösa kiseloxidpartiklar användes som bärare av det aktiva ämnet vilket i detta fall var o-‐vanillin. För att fylla partiklarna löstes vanillinet i ett lösningsmedel och partiklarna tillsattes. Det aktiva ämnet adsorberas på porernas ytor inne i partikeln. Partiklarna separerades sedan från vätskan med vanillinet kvar i porerna. De fyllda partiklarna belades sedan med en tensid (natrium dodecyl sulfat, SDS), ett polymerlager
(polyethleneimin, PEI) och ett silikalager (tetraetyl ortosilikat, TEOS). Beläggningarna utfördes på ungefär samma sätt. Respektive beläggningsämne löstes upp i ett
lösningsmedel där partiklarna sedan tillsattes under omrörning. Efter centrifugering och tvätt separerades de belagda partiklarna för att torka. Termogravimetrisk analys (TGA) användes för att bestämma mängd adsorberad polymer på partikelytan. UV/VIS
spektrometer använder för analys av frisättningshastigheter.
Vid optimering av processen kunde SDS uteslutas. En adsorptionsisoterm för PEI på tomma partikelar visade att då partikelytan var mättad var ca 10 % av den totala vikten polymer. Med större mängd PEI och TEOS på partikeln blir inkapslingen av det aktiva ämnet bättre och frisättningshastigheten minskas. En betydligt mer kontrollerad beläggningsprocess erhölls då det aktiva ämnet löstes i alla omgivande
beläggningslösningar under processen då det bidrog till lägre läckage. Slutligen bevisades att processen är skalbar då partikelkoncentrationen ökades från 4.72 % till 16.5 %.
Table of Contents
1. Aim of this work ... 5
2. Introduction ... 6
2.1 Colloidal stability, instability and agglomeration ... 6
2.1.1 Electric double layer ... 6
2.1.2 Electrostatic stabilization ... 7
2.1.3 Steric stabilization ... 7
2.1.4 Agglomeration ... 7
2.2. Loading and release of the active ... 8
2.2.1 Loading of an active ... 8
2.2.2 Release of an active ... 9
2.3 Applications ... 10
3. Materials and methods ... 11
3.1 Chemicals ... 11
3.2 Methods ... 11
3.2.1 Loading of particles ... 11
3.2.2 Coating the particles ... 11
3.2.3 Analysis ... 12
4. Experiments ... 14
4.1 SDS ... 14
4.2 Adsorption isotherm of PEI ... 14
4.3 Coating with TEOS ... 15
4.4 Increased particle concentration ... 16
5. Results ... 17
5.1 SDS ... 17
5.2 Adsorption isotherm – PEI ... 17
5.3 Release rate of o-‐vanillin from PEI coated composite particles ... 18
5.4 Encapsulation with TEOS ... 19
5.5 Increased particle concentration ... 21
6. Discussion ... 23
6.1 SDS ... 23
6.2 Adsorption isotherm PEI ... 23
6.3 Encapsulation with TEOS ... 25
6.4 Increased particle concentration ... 27
7. Conclusions ... 29
8. Suggestions for further work ... 31
9. Acknowledgements ... 32
9. References ... 33
1. Aim of this work
The aims of this diploma work are as follows:
• To study if this coating process is scalable by increasing the particle concentration from 5 % to over 10 %.
• To coat particles with as low leakage of the active as possible. • To optimize the coating parameters.
• To document the process.
2. Introduction
Controlled delivery and release of active compounds have become an area of huge interest both industrially and academically. For instance the taste of a chewing gum is lost within a few minutes. If you could control the release rate of the active providing taste say for one hour, a market opportunity will arise for producers of chewing gums. Microbial control on growth of mold on painted houses, barnacle growth in the sea and so on can be achieved for limited time periods today. One reason for loss of surface protection is that the biocides protecting the surface simply leach out of the coated surface too fast. A slower release of the biocide would prolong the protection of the surface.
If the process of loading and coating these particles could be done with increased concentration it would be scalable. In this work we will investigate whereas that is possible and also try to achieve as low leakage of the active compound as possible. Below, some theory is described about the parameters that need to be taken into account.
2.1 Colloidal stability, instability and agglomeration
A colloidal dispersion is a heterogeneous system where particles are dissolved in a solution and remains dispersed. An example of a colloidal dispersion is dust in air or as in this case, silica particles in water. A colloidal dispersion can be stable or unstable. A stable colloidal system is well dispersed without any agglomeration of the particles. An unstable dispersion tries to decrease the total energy of the system. One way is due to agglomeration of the particles. As agglomeration occur, the surface/bulk energy ratio decreases. Small particles that have a high energy ratio agglomerates to bigger clusters. The ratio is thereby reduced and the total energy of the system is decreased.
Aggregation may also occur due to attractive van der Waals forces. If polar particles are close enough they arrange themselves so that aggregation can occur as an attempt to decrease the energy of the system. To describe the mechanisms of stability and instability more in detail, the electric double layer of a charged particle will be described.
2.1.1 Electric double layer
When a charged particle is in a polar solution containing ions, the counter ions will be attracted to the particle and the co ions will be repelled. The counter ions are strongly attracted to the surface and form a rather hard, compact, immobile layer close to the surface. Further away, the ions are more mobile. The counter ions want to be close to the surface, but the maximization of entropy wants the ions to be distributed evenly in the solution. This competition occur in the diffuse layer where the counter ion
concentration drops from a high value close to the particle surface down to the equilibrium ion concentration in the solution further away from the surface, (1). We show In Figure 1 the charge distribution of ions around a negatively charged particle.
Figure 1 The electric double layer is schematically described for a negatively charged particle. 2.1.2 Electrostatic stabilization
Colloidal dispersions tend to aggregate due to attractive van der Waals forces. In a polar solvent where some molecules have permanent dipoles they structure themselves so that attraction occur. The dipoles induce dipoles in other molecules as well, which results in further attraction. However, it is possible to overcome agglomeration by long-‐ range repulsive forces like electrostatic repulsion. If the electric double layer of two particles starts to overlap and has the same charge, repulsion occurs. This is called electrostatic stabilization and occur only if the repelling force is stronger than the attractive van der Waals force. (2)
2.1.3 Steric stabilization
Steric stabilization requires adsorption of polymers on the particle surface. Adsorption is a spontaneous process, which means that Gibbs free energy is below zero, see Eqn (1). Even if the process is spontaneous, it is a risk that desorption of the adsorbent occur if the coated particles collide.
∆𝐺 = ∆𝐻 − 𝑇∆𝑆 (1)
Gibbs free energy can be divided into an enthalpy part and an entropy part. When particles collide, the attached polymer chains are compressed which reduces the
available configurations for the chains, leading to a decreased entropy. With decreasing entropy, ΔG increases, which indicates that it is not preferable for the polymers to be in touch with each other.
Water molecules that are adsorbed on the polymers are released in a collision. The release increases the entropy so that Gibbs free energy is decreased and agglomeration
is less favorable. (2)
2.1.4 Agglomeration
As it costs energy to have particles spread in a solution agglomeration occur to decrease the total energy in the system. Agglomeration can happen in many ways and below some of them are explained.
Homocoagulation is when particles of the same charge coagulate. This often occur if the electrostatic repulsion is weak and can be induced by changing pH or salt concentration. By changing pH, charges may change or become neutral, which may lead to less
repulsion. When salt concentration is increased, the screening effect increases which also favors aggregation (1,3).
When particles of opposite charge coagulate, it is called heterocoagulation. As small, strongly charged polymers adsorb on oppositely charged colloids, patches of opposite charge may form on the particle surface. Patches of oppositely charges on different particles can bind to each other and cause patch flocculation. When large polymers bind to more than one particle, the polymer bridge binds the particle together and
aggregation occurs. This mechanism is called bridging flocculation.
Another type of agglomeration is depletion flocculation. In a solution with free polymers and free uncoated particles the particles can come closer to each other than the
diameter of the polymer, and nothing but almost pure solvent is in the space between the particles. This very small volume of almost pure solvent has a higher potential than the solvent in the bulk, and therefore it will diffuse out to the surroundings and the particles are forced together.
The character of the solvent is another parameter to have in mind. If the solvent is bad, the solubility of the particles is low and it is therefore preferable for the particles to be with each other rather than with the solvent. For a good solvent, the particles are fine to have a lot of contact with the solvent and agglomeration is not favored. (4)
2.2. Loading and release of the active
An active is a compound that has a specific function. It can be a drug for pharmaceutical use, an anti-‐mold compound in paints etc. To optimize the performance the active should reach the target and be used at lowest possible effective concentration. It can be achieved by incorporation of the active into different types of carriers. Controlled release can be obtained by encapsulation of the active substance. There are different ways to achieve these encapsulation and some examples are described below. 2.2.1 Loading of an active
An active can be carried in different types of delivery vehicles. An example is
encapsulation by a microsphere. To achieve a filled microsphere, the active is dissolved in-‐situ in the process. Coacervation or phase separation of polymer and active occur as the active is dissolved in a solvent. Other methods are built on self assembly techniques, as for lipids or block polymers. For all these methods, the solvent is evaporated and the amphiphillic molecules close up around the active. As the solvent is totally evaporated, spheres, or other encapsulating shapes, are generated with the active inside. Capsules of surfactants often result in fast release whereas block polymers generate a more
sustained release.
property is to achieve a material with controlled pore size distribution. Two examples where the pore size is well controlled are ordered inorganic mesoporous materials and metal-‐organic framework. The most studied inorganic porous material is silica where common pore structures are hexagonal and bicontinous cubic. Mesoporous silica has preferable properties as an inert and non-‐toxic material and is used as a carrier in drug delivery.
Metal organic frameworks consist of a network of metal ions that are connected by a stiff organic molecule. The most common metal ions are Zn2+ and Cu2+ as di-‐ and three-‐
carboxylates are often used as organic molecules. These materials are crystalline and studied for storage of hydrogen and methane and are a recent research topic for drug delivery applications. (5)
A common way to load porous particles with an active is to dissolve the active in a solvent where it is completely dissolved. The particles are then added and the mixture is stirred for about 24 hours. The active is going into the pores by diffusion, and adsorbs on the internal and external surfaces until equilibrium is reached. Centrifugation separates the particles from the solvent and a washing step follows to remove all residues (6).
2.2.2 Release of an active
Many parameters affect the release rate of a polymeric encapsulated active. As the active diffuses out through voids in the shell, the morphology of the microcapsule is of big importance. The thicker the shell is, the longer will the diffusion length be for the active, which lowers the release rate. If the active has a low solubility in the coating the release rate will be lower than for good solubility. (7) If the shell is porous, the release is fast. To sustain the release of an active in a polymeric capsule, the diffusion coefficient can be minimized. Equation 2 describes the parameters that affect the diffusion coefficient; D. D0 is the free diffusion of the active. The porosity is described as ε and the tortuosity, τ,
describes the trajectory of the diffusion. The pore size is of big importance and is
included in KS where rp is the pore size and ri is the size of the active, eqn 2 and 3. As the
active can interact with the coating by coordinate interactions or hydrogen bonds and a small fraction stays in the shell, described by KBeq. There is a number of binding sites in
the shell and is described as the concentration cB. Combining KBeq and cB. gives us KB, eqn
4. 𝐷 = 𝐷!!!𝐾!𝐾! (2) 𝐾! = (1 − 𝜆)! = (1 −!! !!) ! (3) 𝐾! = (1 + 𝐾!!"𝑐!)!! (4)
Inorganic capsules are not permeable and the diffusion occurs through the pores. When the pore size is increased, the release rate increases. As the particles are small, the ratio of pore opening to particle volume is increased which favors release. Molecules can be
attached on the surface inside the pores and interact with the active to slow down the release. The release rate can be decreased by adding a polymer layer around the particle that acts as a lid on the pore openings. By that, the release rate is dependent on the properties of the inorganic particle as well as the properties of the polymer coating described earlier. (5)
As a particle is encapsulated with a polymer coating, the amount of adsorbed polymer is often presented with an adsorption isotherm in a graph. The adsorbed amount is plotted against pressure or concentration of the active in the solution. When the curve levels out, all available sites on the surface are taken and no more adsorption occurs. The isotherms can show different character, for example the formation of monolayer or multilayer and if the adsorption is strong or weak. An optimal isotherm for a formation of a monolayer is a steep slope in the beginning that flatten out as the surface is
saturated.
2.3 Applications
In many applications, controlled release of an active compound is an important factor. One example is drug delivery, where it is preferable if the active substance is released close to the target. Another example is chewing gum, where controlled release of the flavoring agent could extend the time that the chewing gum tastes. Also, paints can extend their lifetime if the release rate of mold controlling active is decreased.
In this project, silica particles are used. Commercial porous amorphous silica particles are preferable in many ways; they are safe for human health, exist in huge quantities and the pore size is possible to control. Silica as a porous material has low density, large pore volume and a high specific internal surface area. The inner surface area of the pores can be 100-‐1000 m2/g whereas the external surface area is about 1-‐2 m2/g. Depending on
the production process, the pore size and pore size distribution can be controlled. This makes it preferable for the role as a carrier of an active. (8)
3. Materials and methods
3.1 ChemicalsThe chemicals used in this project are shown in Table 1 were also the properties of interest are mentioned. The used recipe and ingredients are from a recipe that SP used in another project and needs to be optimized.
Chemical and supplier Molecular structure Properties of interest
Porous silica SD 4859, PQ Corporation
Particle size 3 μm, pore
volume 2 mL/g Sodium dodecyl sulphate
(SDS), Sigma Aldrich
288.372 g/mole
Polyethyleneimine 1800 (PEI), Aldrich chemistry
1800 g/mole
Tetraethyl orthosilicate (TEOS), Aldrich chemistry
Negatively charged above pH 2-‐3.
Ortho vanillin, Aldrich chemistry 152.15 g/mole Solubility 4.5645 g/L water
Hydrochloric acid, Analar
Normapur 37 %
Ethanol, Solveco 95 %
Table 1. The chemicals used in this project are listed and some properties of interest are mentioned. 3.2 Methods
An original recipe is used for loading silica particles with an active and coating them with three different layers. The processes of loading and coating are described below. 3.2.1 Loading of particles
When loading particles, the active is dissolved in acetone and silica particles are added to the solution. The active absorbs into the pores of the particles. The solution is stirred for 10 minutes and placed in an ultrasonic bath for 30 minutes. The particles are
filtrated from the solution and left to dry in air. Filled particles are further called composite samples.
3.2.2 Coating the particles
The first layer consists of SDS. The surfactant is dissolved in NaCl solution (0.1 M). Particles are added to the solution and put in to an ultrasonic bath to improve
The second layer is cationic PEI. The polymer is first dissolved in NaCl solution and the particles are added. The mixture is stirred for 30 minutes followed by centrifugation. For the silica encapsulation, TEOS is added to a solution of ethanol and hydrochloric acid and left to stir for 1 hour. The PEI coated particles are added to the negatively charged TEOS solution and pH is changed to pH 4 with NH4OH.The mixture is stirred on a “shake
table” for 3 days to cover the particles with silica. After three days the solution is
centrifuged, washed three times with a 1:1 ethanol/water solution and then left to dry at room temperature.
3.2.3 Analysis
The Thermogravimetric analyzer, Pyris 1 TGA, is used to analyze the adsorbed amount on the particles. The TGA calculate the weight loss in percent of the composite particles that are heated to a certain temperature with a controlled rate of heating.
The UV/VIS spectrometer, Lambda 650, analyze the release rate of the active from the loaded particles. Deareated Milli-‐Q water is pumped through the spectrometer with a flow rate of 6.09 ml/min and back to the bottle. The composites are added to the water and the active starts to diffuse out from the pores into the solution. A filter with pores of 0.45 μm is placed at the inlet to prevent particles to go through the spectrophotometer. As the solution pumps through the spectrometer, absorption is measured at 262 nm, which is the specific wavelength for o-‐vanillin. The experimental setup is schematically described in Figure 2. This setup was used for the PEI coated samples. As a TEOS layer was added, no pump was used. Instead 1 ml sample was taken out every hour with a syringe through a filter.
Figure 2. Experimental setup for analysis of the release rate on filled particles.
Table 2. The original recipe for loading and coating of the particles is described shortly.
Loading of particles
Dissolve o-‐vanillin in acetone, 10 wt % Add 1 g particles
Stir for 10 min, ultrasonic bath for 30 minutes Filtration with Büchner funnel
Coating particles -‐ PEI
Dissolve 20 mg SDS in 20 ml water (0.1 M NaCl) Add 1 g particles
Ultrasonic bath for 1 min, washing with water (0.1 M NaCl) PEI dispersion: add 1 mg PEI to1 ml water (0.1 M NaCl) 1 g particles for 20 ml PEI dispersion
Stir for 30 minutes
Centrifuge 3500 rpm in 5 minutes
Wash with water (0.1 M NaCl), 20 ml per g particles
Silica encapsulation
Mix 72 ml HCl with 8 ml ethanol, stir for 10 minutes Add 4 ml TEOS during vigorous stirring, stir for 1 h Add the PEI coated particles
With NH4OH, adjust to pH 4 Stir for three days
Centrifuge, 3500 rpm for 5 minutes Wash three times with 1:1 ethanol:water Leave to dry in room temperature
4. Experiments
In order to optimize the original recipe for loading and coating the particles, some of the process steps were investigated. Furthermore, the particle concentration was increased to check if the recipe is scalable.
4.1 SDS
We checked the impact of the surfactant SDS on agglomeration, particles where coated either with SDS or PEI or a mixture of SDS and PEI. The samples were analyzed with TGA and the turbidity was measured with a spectrophotometer to see if agglomeration
occurs in the absence of SDS.
In order to measure the turbidity, a NaCl-‐solution (0.1 M) with SDS (1 g/L NaCl solution) was put into a spectrophotometer and a wavelength scan were conducted in
transmittance mode. The wavelength chosen for turbidity measurement was one where no absorption occurred.
4.2 Adsorption isotherm of PEI
We checked when the particle surface is saturated with PEI, a number of solutions containing different ratios PEI/particles were prepared, all without SDS addition. The amount of particles was held constant but the amount of PEI was varied. This was done for both empty and loaded particles. For loaded particles, samples were done with the active dissolved in solutions in the coating process (to avoid leakage of active during the process). The active was dissolved in the NaCl solution, 1.52 g/L water and it had to be heated to 70 ͦC to be completely dissolved. We used this solution as washing solution and as solvent for PEI.
PEI/particle ratios for each batch are shown in Table 3, Table 4 and Table 5. Apart from the batch containing dissolved active in the surrounding solutions, the coating process was performed as described in section 5.2.2.
Concentration
PEI (g/L) Empty particles (g) PEI/particles (g/g)
0.20 0.250 0.01 0.80 0.250 0.03 2.05 0.251 0.08 4.00 0.250 0.32 8.03 0.250 0.40 10.00 0.250 0.56 14.00 0.251 0.81 20.17 0.250 1.08 27.05 0.250 1.08
Table 3. Concentrations and ratio PEI (g)/particles (g) for adsorption isotherm of empty particles
Concentration PEI (g/L) Loaded particles (g) PEI/composite (g/g) 0.21 0.249 0.01 0.49 0.505 0.02 0.81 0.254 0.03 1.54 0.251 0.06 3.98 0.251 0.16 8.07 0.253 0.32 10.02 0.250 0.40 14.13 0.253 0.56 26.57 0.253 1.05 27.03 0.250 1.08 50.47 0.507 0.10 83.50 0.500 3.34
Table 4. Concentrations and ratio PEI (g)/sample (g) for adsorption isotherm of loaded particles. Concentration PEI (g/L) Loaded particles (g) PEI/composite (g/g) 0.21 0.250 0.01 0.81 0.251 0.02 2.03 0.254 0.03 3.98 0.251 0.06 7.99 0.250 0.16 10.02 0.251 0.32 14.13 0.250 0.40 27.03 0.252 0.56 26.57 0.252 1.05 50.47 0.249 1.08
Table 5. Concentrations and ratio PEI (g)/composite (g) for adsorption isotherm of loaded particles were the active is dissolved in all solutions.
TGA was used to analyze the amount of PEI that adsorbs on the particle surface. About 2-‐5 mg sample was used per analysis and the temperature interval was from 20-‐900 ͦC and then held constant until the curve became constant. The release rate of the active was analyzed with a spectrophotometer; see the experimental setup in Figure 2. A bottle containing 200 ml deaerated Milli-‐Q water was used for these composite samples.
4.3 Coating with TEOS
TEOS was coated on the PEI layer on loaded particles. To investigate the effect of the TEOS layer on the particles, three different TEOS/composite ratios were prepared, see
Table 6. For every TEOS/composite ratio, two different PEI/composite ratios were used. The coating was executed following original recipe, described in Table 2, where no active was dissolved in the coating solutions. However, for two samples, the active was
dissolved in both TEOS and PEI solutions and for two others; none of the surrounding solutions contained the active. The release rate was analyzed to see the impact of these different parameters.
Vanillin was dissolved in the washing and PEI solution as described in section 4.2. When TEOS solutions were prepared with vanillin, 1.52 g/L was dissolved into the TEOS solution during heating. The mixture was cooled down by stirring for 2 hours before coating of the particles. For the release measurements, bottles with 100 ml Milli-‐Q water were used.
PEI/composite
(g/g) TEOS/composite (g/g) Active in PEI solutions Active in TEOS solution
0.03 1.90 Yes No 1.00 1.90 Yes No 0.03 3.74 Yes No 1.00 3.74 Yes No 0.03 5.5 Yes No 1.00 5.5 Yes No 1.00 3.74 Yes Yes 0.03 5.5 Yes Yes 0.03 5.5 No No 1.00 3.74 No No
Table 6. The samples containing loaded particles coated with different amounts of PEI and TEOS.
4.4 Increased particle concentration
As the particle concentration was increased, two different PEI/composite ratios were used, see Table 7. Both the chosen ratios correspond to when the surface of the particles is completely covered with PEI. These ratios will show if it is a difference between just completely covered surfaces and completely covered.
No SDS was used in the coating process. Because of the viscous solutions at high particle concentration magnets were used for stirring instead of the shaking table. These
samples were prepared without SDS and with the active solved in all solutions. As the release rate was studied, the samples were dispersed in 100 ml Milli-‐Q water and samples were taken out once per hour.
PEI/composite (g/g) Particle concentration (%) 0.50 4.72 0.51 8.99 0.50 12.88 0.50 16.50 1.01 4.72 1.01 8.99 1.00 12.88 1.00 16.50
Table 7. Particle concentration in PEI solutions for two different PEI/sample ratios.
5. Results
5.1 SDS
We made turbidity measurements to check whether the surfactant SDS improve the dispersion of silica particles in solution or not. The chosen wavelength was 450 nm and we measured the transmittance. The transmittance did not change significantly over time and therefore we calculated the average values. Furthermore the non-‐filled composite particles containing silica, PEI and SDS were analyzed with TGA. But as SDS and PEI evaporate at about the same temperature, it was impossible to calculate the respective amount of each component. However, the total weight loss was calculated from the TGA data, see Table 8.
Sample % Transmittance Total weight loss during heating, 20-‐900 °C
Particle + SDS +
PEI 80.58
4.9 %
Particle + PEI 82.86 4.6 %
Table 8. The average of % transmittance for PEI coated particles with and without SDS. 5.2 Adsorption isotherm – PEI
We investigated the amount of PEI that adsorbs on the silica particles. In the coating process, empty particles were exposed to solutions containing different amounts of PEI. The adsorbed amount of PEI was calculated from TGA data where the total weight loss between 214-‐900 °C was measured. As the temperature reached 900 °C it was held there until the curve flattened out. The adsorption isotherm is constructed by plotting the total percentage of adsorbed PEI (on the particles) against the concentration of PEI in the coating solution in Figure 3.
Figure 3. The adsorption isotherm for PEI on empty particles plotted against the initial PEI concentration. We made an attempt to construct an adsorption isotherm for loaded particles in the same way as for empty particles. Unfortunately it was not possible to separate vanillin from PEI in the TGA graph and therefore, the respective adsorbed amount of PEI could
-‐2 0 2 4 6 8 10 12 0 10 20 30 40 50 60 70 80 90 % PE I a ds ob ed PEI concentra:on g/L
not be calculated. Even as we calculated the total amount of PEI + vanillin no significant trend was observed and no adsorption isotherm could be constructed.
5.3 Release rate of o-‐vanillin from PEI coated composite particles
The release rate of o-‐vanillin was analyzed for loaded particles coated with different amounts of PEI. The preparation of these samples were made both with and without o-‐ vanillin dissolved at the coating stage. In Figure 5, we plot the amount of released vanillin against time. The assumption made is that all vanillin is released when the absorbance become constant. In this case no vanillin was added to the PEI solution during the particle coating stage. In Figure 5 we plot the amount of released vanillin against time. In this case vanillin was added to the PEI solution during the particle coating stage.
Furthermore, the absorbance of the active at 100 % release is normalized against 1 gram composite particles and reported in Table 9. We vary the amount of PEI in these graphs and table.
Figure 4. The percentage released o-‐vanillin as a function of time. No vanillin added to the PEI particle coating solution.
Figure 5.The percentage released o-‐vanillin as a function of time. Vanillin was added to the PEI particle coating solution. 0 20 40 60 80 100 0 20 40 60 80 100 120 140 % Re le as e t (min)
Release -‐ no vanillin in coa:ng solu:ons
No PEI-‐coa`ng 0,159 g PEI/g composite 0,3196 g PEI/g composite 0,5653 g PEI/g composite 1,054 g PEI/g composite 0 20 40 60 80 100 0 20 40 60 80 100 120 140 % Re le as e t (min)Release -‐ vanillin in coa:ng solu:ons
No PEI-‐coa`ng 0,032 g PEI/g composite 0,321 g PEI/g composite 0,400 g PEI/g composite 0,558 g PEI/g composite 1,082 g PEI/g composite
PEI/composite (g/g) No active in solutions
Abs(100%)/g sample PEI/composite (g) The active in solutions
Abs (100%)/g composite 0.03 8.07 0.03 4.96 0.16 12.42 0.32 3.12 0.32 24.80 0.40 3.03 0.40 5.86 0.57 0.16 0.56 6.89 1.07 1.04 0.81 6.86 1.05 5.40 1.08 3.17
Table 9. Absorbance at 100 % release per gram composite particles are listed for PEI coated particles with and without the active dissolved in the PEI coating solutions.
5.4 Encapsulation with TEOS
The release rate of the active o-‐vanillin was analyzed for PEI and TEOS coated particles. Absorbance was measured as a function of time as the samples were exposed to water. In Figure 6, the percentage release of active as a function of time is shown. The
assumption is that all active is released when the absorbance become constant. Samples with 0.03 g PEI/composites (g/g) are plotted and only the two highest TEOS contents showed a curve of release. The sample with lowest amount of TEOS did not show any absorbance in the spectrophotometer and is therefore not showed in the plot. In the graph in Figure 7, the absorbance at 262 nm is plotted against time since the curves do not flatten out during the measuring time (up to 24 h). The graph shows PEI/composite particle ratio equal to 1. Only the sample with the lowest content of TEOS did flatten. The two samples with higher TEOS/sample ratio were still increasing in absorbance after 24 hours.
Particles coated with PEI and TEOS were also made with and without the active dissolved in solutions used in the coating processes. When no active was dissolved in solutions, the 0.03 PEI/composite with 3.74 TEOS/composite showed a release curve with a total release at 10-‐20 hours. The corresponding sample with the active solved in the solutions showed the same behavior. The results are schematically described in
Table 10.
Figure 6. The graph shows the release percentage of the active during time for samples containing 0.03 g PEI/g, coated with three different amounts of TEOS.
Figure 7. The graph shows absorbance during time for particles with 1.00 g PEI/g sample, encapsulated with three different amounts of TEOS. Absorbance was measured at 262 nm.
0 20 40 60 80 100 120 0 5 10 15 20 25 30 % Re le as e t (h)
0.03 g PEI/g sample,
Vanilin in PEI solu:ons
3.7 g TEOS/g sample 5.5 g TEOS/g sample 0 0,05 0,1 0,15 0,2 0,25 0,3 0 5 10 15 20 25 30 Ab s, 2 62 n m t (h)
1.00 g PEI/g sample,
Vanillin in PEI solu:ons
1.9 g TEOS/g sample 3.7 g TEOS/g sample 5.5 g TEOS/g sample
PEI(g)/g
sample TEOS (g)/g sample The active solved in coating solutions Abs(100 %)/g Time where the curve plateau (h) Notations 0.03 1.90 PEI Random data points, all with very low absorption, (Abs = 0.02 -‐ 0.05) Failed encapsulation of the active
3.74 PEI 0.07 10-‐20 h 5.50 PEI 0.92 10 h 1.00 1.90 PEI 3.05 10-‐20 h 3.74 PEI
0.87 (t=25h) Does not plateau
5.50 PEI
1.18 (t=25h) Does not plateau 0.03 3.74 No active solved in
any solution 0.11 10-‐20 h 1.00
5.50 TEOS PEI 3.69 About 10-‐20h
Table 10. Data from absorption measurements to analyze the release rate of the active for the different TEOS coated particles
5.5 Increased particle concentration
As the particle concentration was increased during the PEI coating process the samples with highest concentrations became very viscous. All the samples turned brown
overnight during stirring and no visible large aggregates were observed. The release is shown in Figure 9 for the ratios 0.5 and 1.0 PEI (g)/composite particles (g). The
absorbance at complete release per gram composite particles is listed in Table 11.
Figure 8. Graph over the release of the active from particles with increased particle concentration in the coating process , 0.6 g PEI/ g composite.
0 20 40 60 80 100 120 0 2 4 6 8 10 % Re le as e t (h)
0,6 PEI/composite (g/g)
4.72 wt % 8.99 wt % 12.88 wt % 16.50 wt %
Figure 9. Graph over the release of the active from particles with increased particle concentration in the coating process, 1.0 PEI (g)/sample (g).
PEI (g)/ sample (g) % composite in PEI solution Abs (100 %)/g composite (magnet stirrer) Abs (100%)/g composite (Shaking table) 0.6 4.72 24.24 13.79 8.99 8.32 12.88 17.82 16.50 13.69 1.1 4.74 4.06 6.41 8.99 7.30 12.88 8.87 16.50 10.04 Table 11. Absorbance per gram sample.
0 20 40 60 80 100 120 0 2 4 6 8 10 % Re le as e t (h)
1,1 PEI/composite (g/g)
4.74 wt % 8.99 wt % 12.88 wt % 16.50 wt %6. Discussion
6.1 SDS
Regarding the turbidity measurements, the sample with SDS showed a slightly lower transmittance than the sample without SDS. With increasing transmittance, turbidity decreases and the samples are more dispersed. This means that the solution without SDS is just a little more dispersed than the solution with SDS. When heated in the TGA, PEI and SDS seem to evaporate at about the same temperature, which makes it hard to calculate the amount of each substance. However, the total weight loss could be
calculated. The result showed, that the total weight loss excluding water was only slightly higher for the sample with SDS, see Table 8. These results indicate that no SDS, or only little, is adsorbed on the silica surface. The explanation is that SDS is anionic and as silica particles in water with pH above pH 2-‐3, are negatively charged, repulsion occurs. Therefore, the recipe contained no SDS. (2)
6.2 Adsorption isotherm PEI
In the graphs of the adsorption isotherm of PEI in Figure 3, a trend is noticed as the curve can be divided into three regions. First a very strong adsorption, a second where the adsorption is a little less strong, followed by a third region where the curve seems to level out and no more adsorption occurs on the particles as PEI concentration is increased.
The PEI molecules are positively charged and as the silica particles are negatively charged in water above pH 2-‐3, the polymer adsorbs on the particle by electrostatic attraction. (2) A theory behind this behavior is that molecules adsorbs flatly on the particle at low concentrations. When further adsorption occurs, newly arrived polymers pushes the adsorbed ones aside and force them to loosen their grip of the surface. At this stage, the polymers are partly flat against the surface and correspond to region two in the graph. As more polymers adsorb at the surface, they push the adsorbed polymers even more and force them to attach to the particle with just an “arm”, see a schematic scheme in Figure 10.
Figure 10. The adsorption isotherm with the three different regions marked and with describing pictures over how PEI adsorbs to the surface
A driving force for diffusion of active out of particles during the coating process exists. As the concentration of active is much higher inside the particles than in the solution, the driving force for diffusion is high. If the active is dissolved in all solutions, the difference in concentration will not be as big, which decreases the driving force for diffusion. The obtained result of release rate from filled particles is showed in Figure 5. When no active is dissolved in the solutions during the coating process, the release rate increases as the amount of PEI decreases. The opposite trend was seen for the samples were the active is dissolved in the coating solutions. An explanation to this behavior is that vanillin interacts with the PEI coating. As no active is dissolved in coating solutions, the coatings have many sites for adsorption of vanillin. When the amount of PEI
increases on the particle, more vanillin is trapped in the coating. This results in an
increase of trapped vanillin as the PEI amount increases. As a result, less vanillin are free to leak out and the release rate increases with increased amount of PEI.
This implies that the impact of the active in coating solutions is big. Vanillin seems to interact with the coating and prevent further adsorption of the active during the release as the coatings are already saturated with the active. The loading of particles is done with better control if the active is dissolved in all solutions that are in contact with the particles during the coating process.
The type of adsorption of PEI is correlated to the release rate for samples where the active is dissolved in all solutions. At low PEI/composite ratios, the release rate is high when the active is dissolved in coating solutions. As the PEI/composite ratio is
increased, the release rate is decreasing. This can be connected to the diffusion
coefficient. When the polymers are flatly adsorbed on the surface, the tortuosity is low which makes the diffusion coefficient high. As more polymers adsorbs, they are standing
up rather than laying down on the surface, making the tortuosity higher. As the coating gets thicker, the concentration of binding sites in the shell increases which also
decreases the diffusion coefficient. Less leakage occurs as the polymer coating gets thicker.
The absorbance at complete release per gram composite is compared between coated particles with and without the active solved in coating solutions. The samples containing active in coating solutions had narrower distribution of absorbance/g composite. This is a weak indication that a higher amount active can be filled into the particles when the active is dissolved in the process solutions.
6.3 Encapsulation with TEOS
0.03 g PEI/g sample
The samples with a PEI content of 0.03 PEI/composite (g/g), with different amounts of TEOS showed different release behavior. The composite with least amount of TEOS showed very low absorption in the spectrophotometer and the data points did not show any correlation. This indicates that there is, if any, a very small amount of the active in the particles. It is therefore assumed that the adsorbed layer is incomplete and that the active leaks out during the coating process.
However, when the amount of TEOS increases, curves of release rate were obtained, see Figure 7. The sample containing 5.5 TEOS/composite (g/g) shows a more uniform curve compared to the composite with 3.7 TEOS/composite that shows a wider distribution of the data points. That is an indication that the release is more controlled when the
surface is covered with higher amount of TEOS compared to if there are gaps in the TEOS and PEI layers where the active can leak out. Both samples level out at between 10-‐20 hours. As the samples release rates were analyzed for 24 hours and sampling was done hourly, no samples were taken during night. Therefore, it is hard to say exactly when the curve level out.
1.00 g PEI/g sample:
The graphs of release rate, Figure 7, shows that the sample with lowest amount of TEOS level out between 10-‐20 hours whereas the samples with higher TEOS content still showed a linear increase in absorbance at 24 hours. For these samples, the amount of PEI is higher which seems to improve the encapsulation of the active. It is seen that the sample with least amount of TEOS encapsulates the active and achieves a release curve as were for the sample with low PEI content and the lowest amount of TEOS did not show any encapsulation success. It can be assumed that the PEI layer is complete at the PEI/composite ratio of 1.00 and comes with low permeability compared to lower amount adsorbed PEI, as the schematic picture of region 3 shows in Figure 10. The absorption at 100 % release per gram composite is seen in Table 10. For the
PEI/composite ratio 1.00 with 1.90 TEOS/composite, the absorption/g was 3.0485. This value is higher than the values for all the 0.03 PEI/composites. It cannot be compared to the other 1.0 samples as they did not level out. If to take these two values into account, a
