Drug release from heat-treated polyvinyl alcohol films

Abstract

Polyvinyl alcohol (PVA) films containing 10% w/w of a model drug, sulphathiazole, were cast from aqueous solutions and subjected to heat treatment at specific temperatures for known periods of time. Heat treatment at temperatures above the T_g of the PVA films slowed down the rate of drug release from the films. Increasing the temperature of heat treatment from 120°C to 160°C further decreased the rate of drug release. On the other hand, if the heat treatment were conducted at a temperature below the T_g e.g. at 80°C, there were insignificant differences between the release profile of sulphathiazole from heat-treated films and that from untreated films. The duration of heat treatment affected the rate of drug release to a smaller extent compared to the temperature of heat treatment. These results correlated with the heat induced changes in the morphology of, and in the extent of water uptake by the PVA films.     

Electrical properties of evaporated polycrystalline Ge thin-films

Electrical properties of Ge thin films evaporated on Si₃N₄ CVD-coated Si substrate were improved by introducing a heat treatment after the deposition of Ge films. Evaporation conditions were optimized by changing the substrate temperature and deposition rate, and then, heat treatment was performed. At substrate temperatures during the evaporation lower than 300 °C and higher than 400 °C, deposited films were amorphous and polycrystalline, respectively. At substrate temperatures lower than 400 °C, Ge films were evaporated without degrading the surface roughness. The Hall mobility of films evaporated at room temperature increased with increasing the substrate and heating temperature and showed about 400 cm² V⁻¹ s⁻¹ for the hole concentration of 4 × 10¹⁷ cm⁻³ at the heating temperature of 900 °C. This value was almost comparable to that of p-type Ge single crystal.     

The influence of different plasticizers and polymers on the mechanical and thermal properties, porosity and drug permeability of free shellac films

The effect of triethyl citrate (TEC) and different molecular weights and concentrations of polyethylene glycol (PEG), in addition to the effect of different water-soluble polymers and dispersions at different levels, hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), carbomer 940, polyvinyl alcohol (PVA), ethyl cellulose (EC), on the mechanical and thermal properties, drug permeability, and porosity of free shellac films were investigated. Shellac films were cast from aqueous solutions, and their mechanical properties were studied by tensile test. Thermal analyses were performed using differential scanning calorimetry (DSC).

The results showed that the addition of plasticizer caused a decrease in both elastic modulus and glass transition temperature (T_g) and an increase in elongation at break of free shellac films. This effect was related to the concentrations of plasticizers. Different molecular weights of PEGs have different plasticization mechanisms.

Moreover, the incorporation of different amounts of HPMC, MC, or carbomer in free shellac films caused an increase in the flexibility, decrease in T_g, and a marked increase in drug permeability of free shellac films, whereas the addition of PVA caused a decrease in flexibility and drug permeability and an increase in T_g. Addition of EC resulted in a slight decrease of the elasticity and a small decrease in drug permeability. However it does not show a considerable effect on the T_g. In addition, it was found that the drug permeability is directly related to the mechanical properties and T_g of shellac films.     

Effects of substrate temperature on structural, electrical and optical properties of As-doped ZnO films

As-doped ZnO films were prepared by co-sputtering ZnO and Zn₃As₂ targets on glass substrates at various temperatures from 250 to 500 °C. The effects of substrate temperature on structural, electrical and optical properties of the films were investigated. The films grown at temperatures from 250 to 400 °C were c-axis oriented and those deposited above 400 °C exhibited poor crystallinity. Hall measurement showed that p-type ZnO:As films were prepared at different temperatures. With increasing the substrate temperature from 250 to 500 °C, the optical band gap (E_g) first decreased, and then increased. The E_g changes upon the substrate temperature were due to the effect of substrate temperature on the crystallinity of ZnO films.     

Low-temperature growth and orientational control in RuO2 thin films by metal-organic chemical vapor deposition

For growth temperatures in the range of 275°C to 425°C, highly conductive RuO₂ thin films with either (110)- or (101)-textured orientations have been grown by metal-organic chemical vapor deposition (MOCVD) on both SiO₂/Si(001) and Pt/Ti/SiO₂/Si(001) substrates. Both the growth temperature and growth rate were used to control the type and degree of orientational texture of the RuO₂ films. In the upper part of this growth temperature range ( 350°C) and at a low growth rate (< 3.0 nm/min.), the RuO₂ films favored a (110)-textured orientation. In contrast, at the lower part of this growth temperature range ( 300°C) and at a high growth rate (> 3.0 nm/min.), the RuO₂ films favored a (101)-textured orientation. In contrast, higher growth temperatures (> 425°C) always produced randomly-oriented polycrystalline films. For either of these low-temperature growth processes, the films produced were crack-free, well-adhered to the substrates, and had smooth, specular surfaces. Atomic force microscopy showed that the films had a dense microstructure with an average grain size of 50–80 nm and a rms. surface roughness of 3–10 nm. Four-probe electrical transport measurements showed that the films were highly conductive with resistivities of 34–40 μΩ-cm (at 25°C).     

Properties of tantalum oxide thin films grown by atomic layer deposition

Thin tantalum oxide films were deposited using atomic layer deposition from TaCl₅ and H₂O at temperatures in the range 80–500 °C. The films deposited at temperatures below 300 °C were predominantly amorphous, whereas those grown at higher temperatures were polycrystalline containing the phases TaO₂ and Ta₂O₅. The oxygen to tantalum mass concentration ratio corresponded to that of TaO₂ at all growth temperatures. The optical band gap was close to 4.2 eV for amorphous films and ranged from 3.9 to 4.5 eV for polycrystalline films. The refractive index measured at λ = 550 nm increased from 1.97 to 2.20 with an increase in growth temperature from 80 to 300 °C. The films deposited at 80 °C showed low absorption with absorption coefficients of less than 100 cm⁻¹ in the visible region.     

Stresses in sputtered RUOx thin films

RuO_x thin films have been deposited by reactive sputtering in an O₂/Ar atmosphere. The films were characterized for their stress and resistivity as a function of deposition temperature (room temperature, 300°C) and the O₂ content (25–100%) in the sputtering gas. Additionally, the stresses in these films were determined as a function of annealing temperature (up to 600°C) using an in-situ curvature measurement technique. The as-deposited films were found to be under a state of compressive stress for all deposition conditions. The compressive stresses sharply increased with increasing deposition temperature from a value of around 200 MPa at 200°C to 1400 MPa at 300°C. This dramatic increase has been attributed to differences in microstructure at these deposition temperatures. The microstructural differences also led to the widely differing stress-temperature behavior during annealing of these films. For films deposited at temperatures lower than 200°C, the annealing process resulted in a decrease in the compressive stress and resistivity of the films. However, films deposited at a temperature of 300°C did not show any changes in the compressive stress or resistivity after annealing. The results of this study can be used to deposit RuO_x thin films with low resistivity and minimal stresses.     

Preparation and optical properties of sol–gel derived Er-doped Al2O3–Ta2O5 films

Thin films of the system xAl₂O₃–(100 − x)Ta₂O₅–1Er₂O₃ were prepared by a sol–gel method and a dip-coating technique. The influences of the composition and the crystallization of the films on Er³⁺ optical properties were investigated. Results of X-ray diffraction indicated that the crystallization temperature of Ta₂O₅ increased from 800 to 1000 °C with increased values of x. In crystallized films, the intensities of the visible fluorescence and upconversion fluorescence tend to decrease with an increase in x values, due to the high phonon energy of Al₂O₃; the strongest fluorescence is observed in a crystallized film for x = 4 heat treated at 1000 °C. In amorphous films obtained by heat treatment at relatively low temperatures the Er³⁺ fluorescence could not be observed because strong fluorescence from organic residues remaining in the films thoroughly covered the Er³⁺ fluorescence. On the other hand, the Er³⁺ upconversion fluorescence in the amorphous films was observed to be stronger than that in the crystallized films. The strongest upconversion fluorescence is observed in an amorphous film for x = 75 heat treated at 800 °C.     

Investigations Regarding the Determination of Glass Transition Temperatures from Moisture Sorption Isotherms

Moisture sorption isotherm and glass transition temperature (T_g data on polyvinylpyrrolidone (PVP) of molecular weights less than or equal to 40,000 as well as PVP containing added plasticizers were collected to examine the possibility of extracting T, values from moisture sorption data. Moisture sorption isotherms generated for PVP of various molecular weights were similar to those previously reported. The moisture sorption isotherm for PVP-K15 containing added vinylpyrrolidone (VP) and methylpyrrolidone (MP) were predicted reasonably well by simple addition of their respective isotherms with that of PVP-K15. The T_g values for PVP as a function of moisture was similar to that found previously. Decreasing polymer molecular weight or the addition of plasticizers (VP or MP) reduced the T_g of the polymer system, displacing the T_g to lower temperatures. When the moisture content to give a T_g of 25°C (W_g) was indicated on the isotherm, W_g shifted downward with decreasing molecular weight or increasing plasticization by VP or MP while the shape of the isotherm was not distinguishably altered. Consequently, W_g, and thus T_g, would be difficult to extract from the moisture sorption isotherm.     

Growth of SrTiO3 thin films on LaAlO3(001) substrates; the influence of growth temperature on composition, orientation, and surface morphology

SrTiO₃ films have been grown on LaAlO₃(001) single crystal substrates using rf-sputtering. The substrates were held at temperatures ranging from 100 to 850°C. For growth temperatures as low as 350°C epitaxial growth is observed. Below 350°C the films are polycrystalline and three different orientations (100), (110), and (111) can be observed using X-ray diffraction. Atomic force microscopy shows that films deposited at temperatures below 350°C and above 650°C are smooth while the surfaces of the films made at intermediate temperatures are rough and faceted. As growth temperatures decrease below 250°C, the films show decreasing amount of Sr.     

Epitaxial growth of strained Si1−yCy films by the hot-wire cell method and its application to metal oxide semiconductor devices

We succeeded in obtaining strained Si_1−yC_y films at a substrate temperature of 200 °C by the hot-wire cell method. The substitutional carbon concentration in films annealed at 700 °C was 0.9%, while it was limited to 0.13% for a sample grown by gas-source molecular beam epitaxy (MBE) at a substrate temperature of 700 °C. We investigated the thermal stability of strained Si_1−yC_y films for device application. Annealing at over 900 °C caused the formation of 3C-SiC and relaxation of the strain occurred. From this result, we found that the process temperature should be lower than 800 °C. A low-temperature MOSFET process, in which all process temperatures after deposition of Si_1−yC_y were lower than 800 °C, was developed and a strained Si_1−yC_y MOSFET was fabricated.     

Effects of p(O2) and p(CO2) on epitaxial growth of BaTiO3 thin films on MgO(100) substrates by using metal organic acid salts

BaTiO₃ thin films were prepared by using metal organic acid salts on MgO(100) substrates, which have large lattice-misfit with BaTiO₃. Amorphous films prefired at 470°C were crystallized to BaTiO₃ phase by heat treatment at higher temperature. Crystallinity and in-plane alignment of the prepared films were found to depend on the heat-treatment conditions. BaTiO₃ films with high crystallinity but poor (100)-orientation were obtained in air at higher than 1200°C. Whereas, (100)-oriented epitaxial BaTiO₃ film was fabricated by annealing at 900°C under low oxygen partial pressure (p(O₂)). Low carbon dioxide partial pressure (p(CO₂)) is also found to be essential for preparation of epitaxial BaTiO₃ films on MgO substrates by using metal organic acid salts.     

Preparation of Pt-PtOx thin films as electrode for memory capacitors

Pt-PtO_x thin films were prepared on Si(100) substrates at temperatures from 30 to 700°C by reactive r.f. magnetron sputtering with platinum target. Deposition atmosphere was varied with O₂/Ar flow ratio. The deposited films were characterized by X-ray diffraction, X-ray photoelectron spectroscopy and scanning electron microscopy. Resistively of the deposited films was measured by d.c. four probe method. The films mainly consisted of amorphous PtO and Pt₃O₄ (or Pt₂O₃) below 400°C, and amorphous Pt was increased in the film as a deposition temperature increased to 600°C. When deposition temperature was thoroughly increased, (111) oriented pure Pt films were formed at 700°C. Compounds included in the films strongly depended on substrate temperature rather than O₂/Ar flow ratio. Electrical resistivity of Pt-PtO_x films was measured to be from the order of 10⁻¹ Ω cm to 10⁻⁵ Ω cm, which was related to the amount of Pt phase included in the deposited films.     

The effect of storage temperatures on the in vitro properties of a polyanhydride implant containing gentamicin

Septacin® is a biodegradable sustained-release implant containing 20% (w/w) gentamicin sulfate. The matrix of the implant is a polyanhydride copolymer composed of erucic acid dimer (EAD) and sebacic acid (SA) in a one-to-one weight ratio. The effect of storage temperatures (-15°C and 25°C) on the stability of Septacin® was evaluated with respect to gentamicin potency, copolymer molecular weight, and in vitro drug release. The drug in polymer matrix was stable for at least 12 months when stored at 25°C, but the molecular weight of the copolymer declined rapidly at this temperature. At -15°C, there was no change in the molecular weight of the copolymer. However, the placebo (copolymer without gentamicin) exhibited a significant drop in copolymer molecular weight at both temperatures. The drug release profiles showed no change for samples stored at -15°C for the duration of this study, while the release of drug slowed down significantly for samples stored at 25°C for longer than one month. A pronounced difference in the morphology of the -15°C samples and the 25°C samples was observed during the in vitro dissolution test; cracking of the -15°C samples was evident, but the 25°C samples remained intact.     

Influence of substrate temperature on atomic layer growth and properties of HfO2 thin films

Atomic layer growth of hafnium dioxide from HfCl₄ and H₂O has been studied at substrate temperatures ranging from 180–600°C. A quartz crystal microbalance was used for the real-time investigation of deposition kinetics and processes affecting the growth rate. It was shown that the layer-by-layer growth was self-limited at temperatures above 180°C. The data of ex situ measurements revealed that the structure, density and optical properties of the films depended on the growth temperature. The absorption coefficient of amorphous films grown at 225°C was below 40 mm⁻¹ in the spectral range of 260–850 nm. The refractive index of the films grown at 225°C was 2.2 and 2.0 at 260 and 580 nm, respectively. The polycrystalline films with monoclinic structure grown at 500°C had about 5% higher refractive index but more than an order of magnitude higher optical losses caused by light absorption and/or scattering.     

Epitaxial growth of AB type compounds under quasi-equilibrium conditions

Single-crystal films of CdS, CdSe and CdTe have been grown in vacuum on mica (fluophlogopite and muscovite) under isothermal conditions, i.e. with T_ev ≈ T_ep ≈ T_gr where T_ev and T_ep are the evaporation and epitaxial temperatures respectively and T_gr is the growth temperature. The synthesis was carried out in the temperature range 430°–800°C in the case of CdS, 300°–650°C for CdSe and 270°–550°C for CdTe. It is shown that the growth rate of single crystal layers (V_gr) depends exponentially on the growth temperature: V_gr (Å/sec) = D exp (−E/RT_gr) Perfect epitaxial CdS, CdSe and CdTe films have a wide range of electrophysical properties. Co-evaporation of CdS and sulphur and of CdSe and selenium allowed high-resistance films of cadmium sulphide and cadmium selenide of both n- and p-types to be obtained.     

Effect of Temperature of Dissolution on The Release Kinetics of Phenobarbitone from Poly (Dl-Lactic Acid) Microcapsules: Calculation of Activation Energy.

Poly (DL-lactic acid) [DL-PLA] microcapsules containing phenobarbitone (core:polymer, 1:2) were prepared using three different molecular weight polymers, 20,500, 13,300 and 5,200. Buffer pH 9 ware used to study dissolution rate at temperatures of 10°, 15°, 20°, 25°, 30° and 37°C. The release mechanism followed “Higuchi's” square root of time relationship at all these temperatures and allowed calculation of release rate from the straight line portion of release curve. These microcapsules showed an initial burst phase release followed by a lag phase; both of these phases are affected by the temperature of dissolution and polymer molecular weight. The normalized release rate [K_h2/SSA] was found to lower linearly with the lowering of temperature with all three polymers. Arrhenius plot of the normalized release rate allowed calculation of the activation energy (Ea) for the polymers. It was found to lower linearly with the increase in DL-PLA polymer molecular weight.     

Effect of heat on characteristics of chitosan film coated on theophylline tablets

The effect of heat on the characteristics of chitosan film coated on theophylline tablets was studied. Chitosan of high viscosity grade with molecular weight in the range of 800,000-1,000,000, 80-85% degree of deacetylation was used as a film former by dissolving in 1% v/v acetic acid solution. The coated tablets had been cured at 40, 60, and 100°C for 6, 12, and 24 hr. The morphology of the film at the edge and surface of coated tablets was investigated using scanning electron microscopy. Film cracking was increased and clearly observed in the coated tablets cured at 100°C for 24 hr. As a result, more water could be absorbed into the tablets, followed by faster disintegration and faster drug release. The evidence of partial conversion of chitosonium acetate to chitin in the ¹³C nuclear magnetic resonance (NMR) spectra of chitosan films cured at 40, 60, and 100°C was observed, but it had no effect on drug release behavior. Theophylline tablets coated with chitosan films gave sustained release behavior in various media, i.e., distilled water, 0.1 N hydrochloric acid, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer. In addition, the film coating temperature at 55-60°C and curing process at 40 and 60°C had no effect on the drug release from theophylline tablets coated with chitosan polymer. Finally, it might be concluded that both the physical and chemical properties of chitosan films were affected by heat.     

Chemical and electrical characteristics of low temperature plasma enhanced CVD silicon oxide films using Si2H6 and N2O

Silicon oxide films have been deposited at low temperatures in the range of 30–250 °C using Si₂H₆ and N₂O by conventional plasma enhanced chemical vapor deposition technique. The dependencies of deposition temperatures on the film properties are studied. The leakage current and the etch rate of these low temperature films compare favorably to films deposited by silane and TEOS at higher temperatures, respectively.     

Stress variation in epitaxial GaAs films on silicon under thermal treatment

High quality epitaxial GaAs films of 1.8 and 6.3 μm thickness on silicon substrates were examined for lattice distortion, misalignment and curvature by X-ray diffraction (Bond method) at 20–400 °C. These films were deposited by the metal-organic chemical vapour deposition method on the (001) plane of silicon using a buffer layer produced at T_b = 370 or 460 °C. A top layer was then grown at T_t = 560 or 650 °C. The GaAs films contract more strongly on cooling than the substrate, which causes a curvature and a tetragonal distortion below a critical temperature T_c. This temperature varies on thermal treatment at 200–400 °C and approaches T_b, the growth temperature of the buffer layer. The tetragonal distortion can be stabilized, so that T_c approximates T_b, if the GaAs films are annealed for several days at 400 °C.