Valuation of a Cellulose Acetate (CA) latex as coating material for controlled release products

Cellulose acetate (CA) latex plasticized with 150% triacetin (TA) and 120% triethylcitrate (TEC), based on polymer weight, provided dense and homogeneous films when deposited onto propranolol HCl tablets using conventional fluid bed technology. Film permeability to the drug was low and flux/permeability enhancers were added to the CA structure during its manufacture. Films containing 40% surcrose and 10% PEG 8000 were found to provide the best release characteristics in terms of small lagtime (1 hour) and drug release profile (over 12 hours). When sucrose was added to TA or TEC plasticized fimls, a macroporous membrane was created during exposure to the dissolution fluid due to sucrose release from the film. These observations are consistent with the controlled porosity walls previously described for CA films deposited from organic solvents. It was postulated that drug mass transport occurs mainly within the porous CA structure and the mechanism responsible for its is a combination of molecular diffusion/osmotic pressure via water transport into the porous cellulose acetate membrane. Plasticizer loss during drying had also been demonstrated and related to the change in release profile seen with drying time.     

An Investigation Into the Formation of Plasticizer Channels in Plasticized Polymer Films

Abstract

The effects of plasticizer, polyethylene glycol (PEG-600), on the sucrose permeability, void volume and morphology of cellulose acetate free films were investigated. The sucrose permeability of cellulose acetate free films was found to decrease with increasing PEG-600 to a minimum and increase dramatically when they were plasticized by over 30% (w/w) PEG-600. The decrease in sucrose permeability of cellulose acetate free films with increasing plasticizer at low plasticizer concentrations could be interpreted by the antiplasticization effect, and the dramatic increase of sucrose permeability of cellulose acetate free films at high plasticizer level could be explained by the formation of plasticizer channels. The void volume of cellulose acetate free films were calculated by determining the water content in the films, and the effect of PEG-600 on the morphology of cellulose acetate free films was studied by using the scanning electron microscopy (SEM). Both the void volume and SEM studies supported the assumption that the plasticizer channels would be formed in the polymer films which contain high concentration of plasticizer.     

An Investigation Into the Formation of Plasticizer Channels in Plasticized Polymer Films

The effects of plasticizer, polyethylene glycol (PEG-600), on the sucrose permeability, void volume and morphology of cellulose acetate free films were investigated. The sucrose permeability of cellulose acetate free films was found to decrease with increasing PEG-600 to a minimum and increase dramatically when they were plasticized by over 30% (w/w) PEG-600. The decrease in sucrose permeability of cellulose acetate free films with increasing plasticizer at low plasticizer concentrations could be interpreted by the antiplasticization effect, and the dramatic increase of sucrose permeability of cellulose acetate free films at high plasticizer level could be explained by the formation of plasticizer channels. The void volume of cellulose acetate free films were calculated by determining the water content in the films, and the effect of PEG-600 on the morphology of cellulose acetate free films was studied by using the scanning electron microscopy (SEM). Both the void volume and SEM studies supported the assumption that the plasticizer channels would be formed in the polymer films which contain high concentration of plasticizer.     

In Vitro Characterization of Polymeric Membrane used for Controlled Release Application

The application of a polymer film coat is a common practice in the preparation of controlled release dosage forms. In vitro characterization of the polymeric membrane is essential for optimization of the membrane formulation. Polymers selected in this study were cellulose acetate (CA), ethylcellulose (EC) and copolymers of acrylic and methacrylic esters (Eudragit RL100). Plasticizers used in this study were dibutyl sebacate (DBS), triethyl citrate (TEC) and triacetin. Polymer dispersions containing different plasticizers were cast into membranes on a tefloncoated plate. The resulting membranes were evaluated for permeability and mechanical properties. Membrane permeability was determined by quantifying the transport of a model drug, theophylline, across a circular polymeric membrane mounted in a thermostatted, twocompartment horizontal diffusion cell. Mechanical properties of the membranes, such as tensile strength, percent elongation and modulus of elasticity, were determined using an Instron 4301. The results of this study indicate that the CA and EC membranes were found to be effective in preventing the diffusion of theophylline. The addition of Eudragit RL100 to the CA or EC membranes increased the permeability but decreased the mechanical strength of the resulting membrane(s). A significant increase in permeability was observed at a CA:Eudragit RL100 ratio of 60:40. This could be explained by a change in the mechanism of drug transport, principally from partitioning into the membrane to diffusing through the liquidfilled pores of the resulting membrane(s). The results of the mechanical deformation studies indicate that triacetin has a greater potential for partitioning into the CA polymer than does TEC or DBS. DBS has a greater potential for partitioning into the EC polymer than does TEC or triacetin. The addition of Eudragit RL100 to the CA membrane(s) caused a significant decrease in the tensile strength, percent elongation and modulus of elasticity, thus resulting in weaker and softer membranes. The results indicate that the test methods employed were sufficiently sensitive to quantify the test parameters for the changes in membrane compositions which could provide valuable information for optimization of the membrane formulation.     

Studies of the drug permeability and mechanical properties of free films prepared by cellulose acetate pseudolatex coating system

Free films produced with cellulose acetate (CA) pseudolatex were prepared by the casting method. The effects of plasticizer concentration, drying temperature, and drying time on drug permeability and mechanical properties of free films were investigated by three-factor spherical second-order composite experimental design. The results were analyzed by the multivariable regression method. The experimental results indicated that plasticizer concentration, drying temperature, and drying time had complex effects on free film permeability and mechanical behavior. These results probably arise from the film-forming ability of CA pseudolatex particles at various conditions and the evaporation of plasticizer during the film-forming process     

The MiniWiD-Coater. III. Effect of Application Temperature on the Dissolution Profile of Sustained-Release Theophylline Pellets Coated with Eudragit Rs 30 D

Theophylline pellets were coated with Eudragit RS 30 D in a miniature fluid-bed pan coater called MiniWiD developed recently. The dispersions were plasticized with varying amounts of triethyl citrate (TEC), dibutyl phthalate (DBP), and polyethylene glycol 6000 (PEG) and applied at different temperatures ranging from 25 to 45 °C. Theophylline release was tested by dissolution using the USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours.

At a coating level of 4 % (0.7 mg/cm²) sustained-release profiles were obtained from dispersions plasticized with TEC or DBP. By reducing the amount of plasticizer from 20 to 10%, films with higher permeabilities were obtained. This effect was compensated by tempering the pellets at 50 deg;C for 24 hours. The coating temperature had little effect on the dissolution profiles of TEC-plasticized films and no effect on films with DBP.

Coatings plasticized with 20% PEG were applied at temperatures ranging from 25 to 45 °C. These films required a coating level of about 18 % (3.3 mg/cm²) to provide comparable sustained-release properties. In contrast to DBP and TEC, a strong influence of the coating temperature on the release rates was observed in which higher temperatures led to slower release rates. This behavior can be explained by the minimum film-forming temperature (MFT). Since PEG does not lower the MFT of Eudragit RS 30 D, the application of these films below the MFT of 45 °C is associated with a lower degree of film formation.     

The MiniWiD-Coater. III. Effect of Application Temperature on the Dissolution Profile of Sustained-Release Theophylline Pellets Coated with Eudragit Rs 30 D

Abstract

Theophylline pellets were coated with Eudragit RS 30 D in a miniature fluid-bed pan coater called MiniWiD developed recently. The dispersions were plasticized with varying amounts of triethyl citrate (TEC), dibutyl phthalate (DBP), and polyethylene glycol 6000 (PEG) and applied at different temperatures ranging from 25 to 45 °C. Theophylline release was tested by dissolution using the USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours.

At a coating level of 4 % (0.7 mg/cm²) sustained-release profiles were obtained from dispersions plasticized with TEC or DBP. By reducing the amount of plasticizer from 20 to 10%, films with higher permeabilities were obtained. This effect was compensated by tempering the pellets at 50 deg;C for 24 hours. The coating temperature had little effect on the dissolution profiles of TEC-plasticized films and no effect on films with DBP.

Coatings plasticized with 20% PEG were applied at temperatures ranging from 25 to 45 °C. These films required a coating level of about 18 % (3.3 mg/cm²) to provide comparable sustained-release properties. In contrast to DBP and TEC, a strong influence of the coating temperature on the release rates was observed in which higher temperatures led to slower release rates. This behavior can be explained by the minimum film-forming temperature (MFT). Since PEG does not lower the MFT of Eudragit RS 30 D, the application of these films below the MFT of 45 °C is associated with a lower degree of film formation.     

Properties of Aqueous, Plastic Izer-Containing Ethyl Cellulose Dispersions and Prepared Films in Respect to the Production of oral Extended Release Formulations

Plasticized aqueous ethyl cellulose (EC) dispersions (Aquacoat^R ECD-30) are incompatible with concentrated electrolytes but stable with nonelectrolytes. The minimum film formation temperature (MFT) decreases with increasing plasticizer content, from 81°C to about 30°C with 20% dibutyl sebacate (DBS) in the resulting film. The plasticiser has to penetrate completely into the EC particles before film formation to obtain optimal plastification, the lowest film formation temperature and high permeability of the resulting film. This takes more than 5 hours with 20% DBS. Films prepared from plasticized dispersion with short standing times show craters of former plasticizer droplets. With increasing plasticizer content the sticking point of the films decreases. The plasticizer induce a high water absorption of the films: more than 30% with 23-26% DBS or diethyl phthalate (DEP). DBS is hardly released from the films within 5 hours, in contrast to DEP. Thus, the absorbed water is completely swelling water in case of DBS and partially also substitution water in case of DEP. The films squeeze out cetylalcohol (CA) and also sodium lauryl sulfate (NaLS) during storage, this may change the permeability of the films. EC contains a small amount of carboxylic groups which explains the pH dependent release of drugs from pellets coated with aqueous EC dispersions.     

Biocomposites based on cellulose acetate and short curauá fibers: Effect of plasticizers and chemical treatments of the fibers

Biocomposites based on cellulose acetate and short curauá fibers were prepared by extrusion on a laboratory scale. The influence on the mechanical and thermal properties of the biocomposites caused by three different plasticizers, dioctyl phthalate (DOP), triethyl acetate (TEC) and glycerol triacetate (GTA), and the chemical treatment of the fibers was evaluated. The fibers were mercerized or extracted with acetone. The efficiency of the plasticizers was determined by their molecular features, however, for some applications DOP can be replaced by less hazardous plasticizers, such as TEC and GTA. The biocomposites presented morphology of fibrils uniformly dispersed in the polymer matrices and higher Young’s modulus, higher thermal dimensional stability and lower thermal conductivity in comparison with the properties of the corresponding plasticized polymer matrices. Moreover, these biocomposites combine mechanical and dimensional properties of dense materials with thermal conductivities of porous and thermally insulating polymers.     

Porous photocatalytically active ZnO films obtained from ethylcellulose modified solutions by spray pyrolysis

Nanocrystalline porous ZnO films are deposited onto alumina foil substrates by polymer-modified spray pyrolysis of zinc nitrate and zinc acetate solutions. The dependence of the concentration of added ethylcellulose and the type of zinc precursor on both the photocatalytic properties and films morphologies is investigated. It is established that the addition of ethylcellulose as a modifier in the spray solution leads to the formation of a porous structure with crystallites sizes about 15 nm, when zinc acetate is used as precursor. These films show better photocatalytic activity for degradation of Malachite Green (MG) dye than the films obtained from zinc nitrate modified solution. The zinc nitrate films exhibit weaker activity for degradation of MG regardless of their smaller crystallite size (8–12 nm). This can be explained with their lower porosity than that of polymer-modified zinc acetate films. It is established that 450 °C is the limit temperature of treatment for the preparation of ZnO films with good photocatalytic activities. This photocatalytic activity in films shows a drop in the comparison to the films treated at lower temperature, due to decreasing of the pore number and deterioration of the surface morphology.     

The MiniWiD-COATER: II. Comparison of acid resistance of enteric-coated bisacodyl pellets coated with different polymers

Neutral pellets were loaded with bisacodyl and enteric-coated with hydroxypropyl methylcellulose acetate succinate (HPMCAS), carboxymethyl ethylcellulose (CMEC), cellulose acetate trimellitate (CAT), and poly(ethylacrylate, methacrylic acid) (Eudragit L 30 D) in a miniature fluid-bed pan coater called MiniWiD. Gastric juice resistance was tested by dissolution using USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours. As a measure of enteric coating quality the USP specifications were used meaning that no more than 10 % of the drug should be released within 2 hours.

Organic-solvent based films of HPMCAS, CMEC and CAT at a coating level of 18 to 25 % provided gastroresistance for more than 6 hours. Aqueous suspensions of HPMCAS and CMEC as well as the ammonium salt aqueous solutions of CAT produced films with a short gastroresistance of below 0.6 hours. By doubling the coating level of water-based HPMCSD films the protection was prolonged to 3.4 h.

Enteric coatings were obtained from all aqueous latex dispersions of Eudragit L 30 D at a coating level of 24 %. The alteration of coating temperature between 25 and 45 °C had no significant effect on the release rates, whereas the variation of type and amount of plasticizer led to a different release rate after 2 hours. Best protection was obtained using films plasticized with 20 % of dibutyl phthalate (DBP) allowing a release of only 4 % of the drug in 6 hours although the application temperature was 15 °C below the minimum film-forming temperature (MFT). All coatings dissolved in artificial intestinal fluid within 15 minutes.     

Effects of plasticizers on the properties of oat starch films

Oat starch films were prepared by casting using glycerol, sorbitol, glycerol–sorbitol mixture, urea and sucrose as plasticizers. The effects of these plasticizers on the microstructure, moisture sorption, water vapor permeability (WVP) and mechanical properties were investigated using films stored under a range of relative humidities. The plasticizer type did not affect significantly (p ≤ 0.05) the equilibrium moisture content of films, except at 90% relative humidity (RH). Films without plasticizer adsorbed less water and showed higher WVP than plasticized ones, indicating the antiplasticizing effect observed in this work. In general, a decrease in stress at break and Young's modulus and an increase in strain at break were observed when RH increased in all film formulations. Films without plasticizer showed higher stress at break values than the plasticized ones and presented stable strain at break under a range of RH. Sucrose films were the most fragile at low RH while glycerol films were the most hygroscopic.     

The MiniWiD-COATER: II. Comparison of acid resistance of enteric-coated bisacodyl pellets coated with different polymers

Abstract

Neutral pellets were loaded with bisacodyl and enteric-coated with hydroxypropyl methylcellulose acetate succinate (HPMCAS), carboxymethyl ethylcellulose (CMEC), cellulose acetate trimellitate (CAT), and poly(ethylacrylate, methacrylic acid) (Eudragit L 30 D) in a miniature fluid-bed pan coater called MiniWiD. Gastric juice resistance was tested by dissolution using USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours. As a measure of enteric coating quality the USP specifications were used meaning that no more than 10 % of the drug should be released within 2 hours.

Organic-solvent based films of HPMCAS, CMEC and CAT at a coating level of 18 to 25 % provided gastroresistance for more than 6 hours. Aqueous suspensions of HPMCAS and CMEC as well as the ammonium salt aqueous solutions of CAT produced films with a short gastroresistance of below 0.6 hours. By doubling the coating level of water-based HPMCSD films the protection was prolonged to 3.4 h.

Enteric coatings were obtained from all aqueous latex dispersions of Eudragit L 30 D at a coating level of 24 %. The alteration of coating temperature between 25 and 45 °C had no significant effect on the release rates, whereas the variation of type and amount of plasticizer led to a different release rate after 2 hours. Best protection was obtained using films plasticized with 20 % of dibutyl phthalate (DBP) allowing a release of only 4 % of the drug in 6 hours although the application temperature was 15 °C below the minimum film-forming temperature (MFT). All coatings dissolved in artificial intestinal fluid within 15 minutes.     

The effect of argon pressure, residual oxygen and exposure to air on the electrical and microstructural properties of sputtered chromium thin films

Chromium thin films were deposited on SiO₂/Si wafers using two sputtering systems with different levels of cleanliness, and at argon sputtering pressures varying between 0.13 and 0.93 Pa. Films from the two systems grown under identical sputtering conditions had significantly different resistivity values that are shown to be due to differences in residual oxygen in the chambers. Electrical transport measurements were conducted on the series of grown films to investigate the influence of argon pressure on film electrical resistivity. The films morphology, microstructure and composition were characterized using scanning electron microscopy and X-ray photoelectron spectroscopy. Significant differences were found in Cr thin films sputtered at different sputtering pressures; differences in resistivity performance and microstructure were noted. This change was shown to be due to the transition from porous structure to a denser microstructure. The Cr films sputtered at high pressure contained large quantities of oxygen when exposed to air. Some of the oxygen is added to the film during the deposition depending on the deposition rate and the base pressure of the sputtering system. The rest is incorporated into the film once it is exposed to air. The amount of oxygen added at this stage depends on the structure of the film and would be minimal for the films deposited at low sputtering pressures.     

Effects of porosity on ferroelectric properties of Pb(Zr0.2Ti0.8)O3 films

The sol-gel deposition method has been successfully applied to obtain Pb(Zr_0.2Ti_0.8)O₃ thin films on platinized silicon wafers. Addition of different amounts (7-15 wt.%) of organic macromolecular polyvinylpyrrolidone in the precursor solution prior to spin coating proves to be an excellent method for obtaining porous films. The crystal structure of as deposited films was analyzed by X-ray diffraction. The porous films show perovskite phase after annealing at 650 °C. The surface morphology has been studied by Atomic Force Microscopy and Scanning Electron Microscopy. The surface profile indicates a roughness of the film of 5 nm and no microcracks on the surface. The ferroelectric behavior was proved for each film, by hysteresis loops and by the “butterfly” shape of the capacitance-voltage characteristics. The remnant polarization and the coercive field decrease while the amount of added PVP increases.     

Variation of composition of an enteric formulation based on Kollicoat MAE 30 D

Using a formulation described previously with Kollicoat MAE 30 D as the film-forming agent, the effect of variations in plasticizer type and quantity and talc concentration on the preparation and processing of spray-coating suspensions and the properties of isolated films and film-coated caffeine tablets prepared using them was investigated. In the preparation and processing of spray-coating suspensions, the plasticizers polyethylene glycol (PEG) 400, PEG1500, and TEC (triethyl citrate) tended to coagulate at all concentrations investigated, while Cremophor RH 40 coagulated above 10% (expressed as a percentage of the mass of the film-forming agent used). Analogous preparations using propylene glycol (PG), PEG6000, and Lutrol F 68, on the other hand, were found to be stable at all concentrations. The instability was not caused by the Kollicoat MAE 30 D polymer dispersion as such, but by interactions between the finely dispersed pigments and other formulation ingredients. Equivalent nonpigmented preparations are stable and do not coagulate. With all the plasticizers investigated, the minimum film-forming temperature (MFT) fell, albeit to differing degrees, as the amount of plasticizer increased. Similarly, the tensile strength of isolated films declined as plasticizer concentration increased, while the reverse was true as regards their elongation at break. Whereas neither the subsequent disintegration time nor the rate of release of active ingredient at pH 6.8 was significantly affected by the various plasticizer additives, the different film-coated tablet formulations with a core containing a powerful disintegrant exhibited varying degrees of permeability to simulated gastric fluid. With PEG6000, permeability increased as the plasticizer concentration increased, while Lutrol F 68 provided an optimum barrier at 20%, and PG provided a good barrier between 10% and 30%. No gastroresistance was obtained with TEC at 10%. Only the best plasticizer formulations were used in the trials with different talc concentrations, namely, those formulations with 20% PEG6000, 20% Lutrol F 68, 20% PG, and 10% PG. When talc was added, the MFT rose, reaching its maximum at 13% talc (as a proportion of the film-forming agent). In the test for gastroresistance, film-coated caffeine tablets without talc absorbed distinctly more acid than those containing talc. Above 27% talc, the acid resistance improved only insignificantly. On the other hand, during this test, only a maximum of 3% of the active ingredient was released into the gastric juice. Of the variants investigated, the formulation with 20% PG and 27% talc performed best.     

单糖对玉米淀粉基复合膜性能的影响

目的研究D-果糖和葡萄糖作为增塑剂对玉米淀粉-壳聚糖复合膜性能的影响。方法糊化后的玉米淀粉溶液与壳聚糖溶液混合,分别添加5%,20%,35%,50%,65%(质量分数)的D-果糖及葡萄糖,均质后流延成膜;测定膜的力学性能,并通过扫描电镜、接触角、傅里叶红外扫描和X-衍射对复合膜相关特性进行表征。结果成膜物质之间相容性好,增塑剂用量由5%增加至65%,膜的厚度增加,经D-果糖和葡萄糖增塑的复合膜抗拉强度分别由73.99,70.88 MPa减至18.08,40.53 MPa。经D-果糖增塑的复合膜断裂伸长率呈递增趋势,在添加量为65%时达到19.03%,经葡萄糖增塑的复合膜呈现递减趋势。结论同一含量下,2种复合膜的厚度相近,抗拉强度相差不大,但经D-果糖增塑的复合膜断裂伸长率高,亲水性较好,更适合作为增塑剂应用在复合膜的制备中。     

Efficacy of Novel Electroless Plating Process for Dense Pd/Cr2O3/PSS Membrane Fabrication

This work addresses the role of chromia diffusion barrier on the combinatorial plating characteristics of Pd plating baths during fabrication of dense Pd/Cr₂O₃/porous stainless steel (PSS) composite membranes and is compared with those obtained during fabrication of Pd/PSS membranes. Cr₂O₃ was deposited by electroplating technique followed with oxidation at 700°C and Pd films were deposited using a novel Pd electroless plating process that provides optimal performance. Apart from providing similar process characteristics, the Pd/Cr₂O₃/PSS membrane provided 15.2% lower Pd film thickness in comparison with Pd/PSS membrane for similar pore densification values.     

Study of mechanical properties,oxygen permeability and AFM topography of zein films plasticized by polyols

The use of plastic for packaging has grown extensively in recent years. In this context, biodegradable films can be a source of energy saving and an important issue for environmental protection. Zein protein (prolamin of corn) is one of the best biopolymers for edible film making and polyols are convenient plasticizers for biopolymers. Polyols (sorbitol, glycerol and mannitol) at three levels (0.5, 0.7 and 1g/g zein) were used as plasticizers and the tensile properties, oxygen permeability (OP) and AFM topography of zein films were studied. Films plasticized by sorbitol had a relatively higher ultimate tensile strength (UTS) than films containing glycerol and mannitol at low levels of plasticizers (0.25, 0.7g/g zein). There was no significant difference between the strain at break values (SB) of films plasticized by sorbitol and glycerol at low levels of plasticizers, while films plasticized by sorbitol had higher SB than the films containing glycerol and mannitol at a high level of plasticizer (1g/g zein). Pure zein films had low oxygen permeability (OP), and increasing the plasticizer level to 0.5g/g zein decreased OP values in films containing sorbitol and glycerol. Films containing sorbitol and mannitol had the lowest and highest OP values, respectively. AFM images were used to evaluate the surface morphology (qualitative parameter) and roughness (quantitative parameter) of zein films. Films plasticized by glycerol had smoother surfaces and a lower roughness parameter (Rq). No relationship between OP values and the roughness of the zein films was observed. Copyright © 2006 John Wiley & Sons, Ltd.     

Leaching of water-soluble plasticizers from polymeric films prepared from aqueous colloidal polymer dispersions

The leaching of water-soluble plasticizers from polymeric films prepared by casting and drying of plasticized colloidal polymer dispersions was investigated with respect to the type and concentration of plasticizer (triethyl citrate or triacetin), film thickness, type of colloidal polymer dispersions (acrylic: Eudragit RS30D, RL30D, or L30D; cellulosic: Aquacoat), Eudragit RS30D/RL30D ratio, and method of film preparation (solvent- or pseudolatex-casting). The leaching increased with increasing level of plasticizer as indicated by an increase in the release rate constant while the release rate constant was independent of the film thickness. The leaching was more rapid from Aquacoat films than from Eudragit RS30D films at all plasticizer concentrations. Increasing the amount of the more hydrophilic polymer dispersion, Eudragit RL30D, in mixed Eudragit RS/RL films increased the rate of leaching. The incorporation of propranolol HCl into the polymeric films significantly increased the leaching rate constant when compared to drug-free films. The leaching from pseudolatex-cast films was faster when compared to the leaching from solvent-cast films due to the denser structure of the solvent-cast films.