Ammonio Methacrylate Copolymer Research Articles

In vitro study of a novel polymeric mesenchymal stem-cell coated membrane

The objective of the study was to develop and study in vitro polymeric membrane that enables adhesion, proliferation and differentiation of mesenchymal stem cells on its surface. We screened several membrane formulations with varying plasticizer types and concentrations for their ability to support MSC adherence and growth. To that end, MSCs were isolated from human bone marrow, and cell adherence to membrane, cell-membrane interaction and cell morphology were observed using scanning electron microscopy (SEM) and fluorescent microscopy. MSCs adhered well to Ammonio Methacrylate copolymer type A (AMCA) membranes prepared with the various plasticizers and revealed spindle monolayer shape with podia, similar to polystyrene dishes. MSCs proliferated and differentiated only on AMCA membrane with polyethyleneglycol 400 (PEG400) as plasticizer. Furthermore, the membrane surfaces were characterized using SEM and their porosity was measured. These data confirm that MSCs maintain their stem cell traits after adhesion to membrane.

Effect of plasticizer on release kinetics of diclofenac sodium pellets coated with Eudragit RS 30 D.

The present study was designed to investigate the effect of two plasticizers, i.e., triethyl citrate (TEC) and polyethylene glycol 6000 (PEG 6000) on the in vitro release kinetics of diclofenac sodium from sustained-release pellets. Ammonio methacrylate copolymer type B (Eudragit RS 30 D) is used as the release-retarding polymer. Both plasticizers were used at 10% and 15% (w/w) of Eudragit RS 30 D. Pellets were prepared by powder layering technology and coated with Eudragit RS 30 D by air suspension technique. Thermal properties of drug and drug-loaded beads were studied using differential scanning calorimeter (DSC). DSC thermogram represented the identity of raw materials and exhibited no interaction or complexation between the active and excipients used in the pelletization process. Dissolution study was performed by using USP apparatus 1. No significant difference was observed among the physical properties of the coated pellets of different batches. When dissolution was performed as pure drug, about 8.22% and 90% drug was dissolved at 2 h in 0.1 N HCl and at 30 min in buffer (pH 6.8), respectively. From all formulations, the release of drug in acid media was very negligible (maximum 1.8 +/- 0.08% at 2 h) but in buffer only 12% and 30% drug was released at 10 h from coated pellets containing TEC and PEG 6000, respectively, indicating that Eudragit RS 30 D significantly retards the drug release rate and that drug release was varied according to the type and amount of plasticizers used. The amount of TEC in coating formulation significantly effected drug release (p < 0.001), but the effect of PEG 6000 was not significant. Formulations containing PEG 6000 released more drug (98.35 +/- 2.35%) than TEC (68.01 +/- 1.04%) after 24 h. Different kinetic models like zero order, first order, and Higuchi were used for fitting drug release pattern. Zero order model fitted best for diclofenac release in all formulations. Drug release mechanism was derived with Korsmeyer equation.

Drug–polymer interaction and its significance on the physical stability of nifedipine amorphous dispersion in microparticles of an ammonio methacrylate copolymer and ethylcellulose binary blend

Using spectroscopic and thermal analysis, this study investigated drug-polymer interaction and its significance on the physical stability of drug amorphous dispersion in microparticles of an ammonio polymethacrylate copolymer (Eudragit RL) (RL) and ethylcellulose (EC) binary blend (RL/EC = 2:1 w/w) prepared for use in controlled release of poorly water-soluble drugs. Solid dispersion of the model drug, nifedipine in the microparticles could be described as an ideal amorphous mixture for drug loadings up to 11% w/w. The antiplasticizing effect of the polymer blend was indicated by a significant increase in the glass transition point from approximately 50 degrees C for the amorphous nifedipine to approximately 115 degrees C for its solid solution. Moreover, shifts in infrared vibration wavenumber of nifedipine carbonyl and amine groups suggested that the hydrogen bonds (H-bonds) originally formed among nifedipine molecules were broken and replaced by those formed between nifedipine and polymers in the microparticles. Further infrared analysis on nifedipine amorphous dispersions with a single polymer, namely RL or EC, confirmed the proposed hydrogen-bonding interactions; and their stability study results suggested that both antiplasticizing effects and hydrogen bonding of EC and RL with nifedipine might be responsible for the physical stability of the microparticles of nifedipine amorphous dispersion with a RL/EC binary blend.

An assessment of the interactions between diclofenac sodium and ammonio methacrylate copolymer using thermal analysis and Raman spectroscopy

The objective of the work was to assess the possible interactions between the model drug diclofenac sodium (DS) and the water-insoluble ammonio methacrylate copolymer (AMC). Films with different drug/polymer ratios were therefore prepared by the solvent casting method and investigated as a preformulation study towards sustained release microparticles. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to investigate the dispersed/dissolved state of the DS in the preparation, the thermal stability and the properties of DS-containing AMC films; and Raman spectroscopy was used to confirm the possible interactions between DS and AMC. Thermoanalytical studies confirmed that the DS could behave as a plasticizer, which was indicated by decreasing glass transition temperature ( T g) of the AMC, depending on its dispersity level in the AMC matrix. Partially solid solutions were formed at DS/AMC ratios of 1:12, 1:8 and 1:6. The DS was mainly crystalline at DS/AMC ratio of 1:4, while it remained crystalline at a ratio of 1:2. The Raman spectra confirmed that none of the major structural changes revealed any significant difference, which can indicate a strong ionic interaction between the DS and the AMC. The investigations provided good facilities for the selection of a DS/AMC ratio, in the preformulation study of the microsphere preparation process, in conformity with the therapeutic aim.

Nifedipine solid dispersion in microparticles of ammonio methacrylate copolymer and ethylcellulose binary blend for controlled drug delivery: Effect of drug loading on release kinetics

In order to elucidate the controlled-release mechanism of a poorly water-soluble drug from microparticles of ammonio methacrylate copolymer and ethylcellulose binary blend prepared by a phase-separation method, nifedipine-loaded microparticles with different levels of drug loading were evaluated by micromeritic properties, drug physical state, matrix internal structure, drug dissolution, and release modeling. Drug release study indicated that nifedipine release from the microparticles followed the Fickian diffusion mechanism, which supported the study hypothesis that as a result of formation of a nifedipine molecular dispersion, nifedipine dissolution inside the matrix was no longer the rate-limiting step for drug release, and the drug diffusion in matrix became the slowest step instead. Moreover, study results indicated that even though drug loading did not significantly affect the microparticle size distribution and morphology, nifedipine release rate from those microparticles was more or less influenced by the level of drug loading, depending on matrix formulation. At lower levels of drug loading, nifedipine release was well described by the Baker and Lonsdale's matrix diffusion model for microspheres containing dissolved drug and nifedipine had a plasticizing effect on the polymers that caused an increase in drug effective diffusion coefficient with increasing drug loading. However, at higher levels of drug loading, probably due to formation of solid nifedipine domains in microparticles, a change in the release kinetics was observed.

Nifedipine Molecular Dispersion in Microparticles of Ammonio Methacrylate Copolymer and Ethylcellulose Binary Blends for Controlled Drug Delivery: Effect of Matrix Composition

ABSTRACTThe objective of this study is to explore matrix-type microparticles, comprising a solid dispersion of drug with an ammonio methacrylate copolymer and ethylcellulose binary blend, for use in the controlled release of a poorly water-soluble drug, nifedipine. Microparticles consisting of an ethylcellulose N7 (N7) and Eudragit RL® (RL) binary blend at different ratios were prepared using phase-separation methodology. The effects of matrix composition on microparticle properties were evaluated by polarized light microscopy, differential scanning calorimetry (DSC), FT-infrared and UV-visible spectroscopy, stability, and drug release studies. Study results indicate that the particle size distribution, particle morphology, and drug release rate from the microparticles were influenced by the ratio of RL to N7. Discrete spherical microparticles with a narrow size distribution and a controlled release profile were obtained when the ratio of RL to N7 was in the range from 1:1 to 2:1 w/w. Solid-state characterization and release kinetic studies on these microparticles confirmed that the nifedipine release from the microparticles followed the Baker and Lonsdale's matrix diffusion model (1974) for microspheres containing dissolved drug, and the nifedipine diffusion in the microparticle matrix was the rate-limiting step. As the ratio of RL to N7 was changed from 0:1 to 4:1 w/w, the effective drug diffusion coefficient in the micro-matrix increased from 5.8 × 10−10 to 8.6 × 10−9 (cm2/h). In addition, probably due to formation of a stable molecular dispersion promoted by hydrogen bonding between nifedipine and the polymers, no significant changes in the nifedipine physical form or release kinetics were observed after 1-year storage at ambient room temperature followed by 3-month accelerated stability at 40°C/75% RH in a closed container.

Preparation and in vitro evaluation of propylthiouracil microspheres made of Eudragit RL 100 and cellulose acetate butyrate polymers using the emulsion-solvent evaporation method

The objectives of this investigation are to evaluate the encapsulation efficiency of the anti-thyroid agent 6-n-propyl-2-thiouracil using two polymers of different characteristics (cellulose acetate butyrate polymer, (CAB-551-0.01) and ammonio methacrylate copolymer (Eudragit RL 100) and to study the effect of this encapsulation on the drug release properties. Polymers were used separately and in combination to prepare different microspheres. Also, the effect of polymer solution phase viscosity was studied for each of the polymers and for their combinations. An Ostwald viscometer was used to evaluate the relative viscosities of polymer solution phases and their combinations. Microspheres with 25% theoretical drug loading of 6-n-propyl-2-thiouracil core material were prepared by the emulsion solvent evaporation method. Microspheres prepared from CAB-551-0.01, which has higher relative polymer phase viscosity than Eudragit RL 100, showed significantly lower drug release rates and a noticeable lag time. Polymer combinations of CAB-551-0.01 and Eudragit RL 100 (1:1) showed an interesting synergistic increase in relative polymer solution viscosities at all concentrations. Unlike microspheres prepared from the two polymers separately which follow Higuchi spherical matrix release kinetics, microspheres prepared using a combination (1:1) of the two polymers showed near zero order with faster rates compared to those prepared using CAB-551-0.01 equivalent polymer concentrations. The results of this study suggest that 6-n-propyl-2-thiouracil was successfully and efficiently encapsulated and release rates of matrix microspheres are related to polymer solution phase viscosity, but when polymer combinations were used other factors such as structural effects must be considered.

Properties of Tablets Containing Granulations of Ibuprofen and an Acrylic Copolymer Prepared by Thermal Processes

The objective of this study was to investigate the properties of tablets containing granulations of ibuprofen (Ibu) and Ammonio Methacrylate Copolymer, Type B (Eudragit RS PO) prepared by hot-melt processing. Tablets were compressed from granules prepared by hot-melt granulation (HMG) or direct compression (DC). For the hot-melt extrusion (HME) process, tablets were prepared by cutting the extrudate, manually. The physicochemical properties of tablets were investigated using thermal analysis, powder X-ray diffraction analysis, tablet hardness, and drug dissolution. The effect of thermal treatment of tablets on the dissolution characteristics of Ibu was also investigated. The results demonstrated that the Ibu lowered the glass transition temperature (Tg) of the Eudragit RS PO and the softened polymer functioned as a thermal binder in the granulation. Ibu was demonstrated to be an effective plasticizer for Eudragit RS PO in the thermal processes. The efficiency of the granulation process increased with increasing levels of Eudragit RS PO in the powder blend. Higher levels of Eudragit RS PO in the tablets prepared by HMG or HME resulted in a decrease in the dissolution rate of the Ibu. An increase in the amount of Ibu in the tablets prepared by HMG or DC led to a decrease in the initial dissolution rate of the Ibu. Following the thermal treatment of the Ibu tablets prepared by HMG, the dissolution rate was significantly decreased due to structural changes in the tablets that resulted from the fusion and coalescence of plasticized polymer particles, causing a reduction in tablet porosity. The Ibu tablets prepared by HME demonstrated minimal changes in their release properties following thermal treatment even at temperatures higher than the Tg of the polymer. HME was shown to be a novel method to prepare matrix tablets and stable dissolution properties were obtained when tablets were stored at 40°C for 30 days.

Transport properties of ionic drugs in the ammonio methacrylate copolymer membranes.

Ammonio methacrylate copolymer is a pharmaceutical excipient widely used as a coating material for encapsulation of pellet and tablet dosage forms. Because of the charged ammonio function groups within the polymer, ionic drugs may interact with the coating film while transporting through it. The kinetic swelling and drug permeation properties of the ammonio methacrylate copolymer membranes were studied to delineate the effect of ionic interaction between the ionic drugs and the membranes. The pH and ionic strength of the solutions and the charged properties of drugs were varied to study the effects on the transport properties through the membranes. Ambroxol was chosen as a model cationic drug and aspirin as a model anionic drug. The degree of membrane swelling in the drug-free solution decreases as the ionic strength increases but it is irrelevant to the pH. With the presence of ionic drugs, the degree of membrane swelling is affected by the drug species as well as the pH of the solutions in addition to the effect of ionic strength. The degree of swelling for a membrane in a solution containing aspirin is higher at a lower pH and ambroxol is lower at a lower pH. Aspirin experiences a three-stage permeation and ambroxol a two-stage one. The ion-exchange reaction between the anionic carboxylic groups in aspirin and the cationic ammonio groups in the membranes results in a slow permeation stage during the transient state. The pseudo steady-state permeability for each drug follows the trend as the degree of membrane swelling in the drug media at various pH and ionic strengths. However, it is much higher for aspirin than ambroxol although the degree of membrane swelling is higher in an ambroxol solution than that in an aspirin solution. The permeability of ambroxol through the membrane is largely reduced because of the Donnan exclusion effect. The interaction between ionic drugs with the cationic groups in the membranes affects the ionic strength of the solutions and results in a pH-dependent degree of swelling. The ionic interaction also determines the drug permeation rates as well as the transient permeation behaviors.

Stabilization and sustained-release effect of Misoprostol with Methacrylate copolymer

The use of ammonio methacrylate copolymer (Eudrgit RS, RL) to form a sustained-release solid dispersion of Misoprostol can improve and enhance two important physical and chemical properties of Misoprostol. First, the solid dispersion matrix formed by the copolymer can protect Misoprostol from being degraded by water so that its stability is improved. Second, Misoprostol can be slowly released by diffusion from the copolymer matrix. Accelerated stability studies of Misoprostol–Eudragit solid dispersion after storing at various temperatures for different time periods were carried out. According to high performance liquid chromatography (HPLC) analyses, the stability of Misoprostol in a series of Eudragit appeared significantly improved at different ratios. The Misoprostol–Eudragit dispersion can be used in a powder form, filled in capsules, or compressed into tablets. The dissolution profiles of Misoprostol–Eudragit solid dispersion and its tablets in water, pH 1.2, 4.5 and 6.8, dissolution media show that this stable solid dispersion is a sustained-release type.

&lt;i&gt;In vitro&lt;/i&gt; Release Kinetics Study of Ambroxol Hydrochloride Pellets Developed by Extrusion Spheronization Technique Followed by Acrylic Polymer Coating

The aim of the present study was to investigate the effect of Ammonio Methacrylate Copolymer Dispersion Type A (Eudragit RL 30 D) and Ammonio Methacrylate Copolymer Dispersion Type B (Eudragit RS 30 D) combination in different weight ratios on the release kinetics of Ambroxol Hydrochloride from coated pellets. Microcrystalline cellulose, lactose, maize starch, hydroxypropyl methylcellulose and the drug was incorporated in the nuclei prepared by Extrusion-Spheronization technique which was coated with Eudragit RL 30D and Eudragit RS 30D in 1:1,1:1.5,1:2,1:2.5 and 1:3 ratios. The in vitro dissolution studies were carried out in 0.1N HCl for 1 hour followed by phosphate buffer (pH 6.8) for 11 h with USP dissolution apparatus Type-II. Drug release decreased with increasing amount of Eudragit RS 30 D in all cases. The drug release followed first order and Higuchi release kinetics. The Korsmeyer plot revealed n=0.50-0.61 or non-Fickian transport mechanism for drug release. From one way ANOVA it was found that the ratio of binary polymer mixer had significant (p &lt; 0.05) effect on drug release. Key words: Aqueous coating, Eudragit, release kinetics, pellet, extrusion-spheronization  DOI = 10.3329/dujps.v7i1.1222 Dhaka Univ. J. Pharm. Sci. 7(1): 75-81, 2008 (June)

Effect of Acrylic Polymers on the Physical Parameters and &lt;i&gt;in vitro&lt;/i&gt; Release Kinetics of Diclofenac Sodium Sustained Release Pellets

The aim of the present study is to investigate the effect of Ammonio Methacrylate Copolymer Type A (Eudragit RL 30 D) and Ammonio Methacrylate Copolymer Type B (Eudragit RS 30 D) on the release kinetics study of diclofenac sodium form coated pellets. Eudragit RS 30 D and Eudragit RL 30 D were added into the formulation at 5:1 ratio. Different percent of this polymeric combination was loaded on to the drug-loaded pellets. Loss on drying value as well as bulk density of coated pellets increase along with the increase in polymer level. It was found that the cumulative percent release of drug decreased with the increase of polymer load in all cases. From all formulations it was observed that the release of diclofenac sodium in 0.1N HCl media was very low (maximum 2.87 %) at first 2 hours. Better sustaining effect was found from Eudragit RS 30 D and Eudragit RL 30 D combinations. Drug was released linearly along with time throughout the whole dissolution process in phosphate buffer (pH 6.8) and it was also revealed that, in all cases the release of diclofenac sodium followed zero order kinetics. &#x0D; &#x0D; Key words: Diclofenac sodium, Eudragit RL 30 D, Eudragit RS 30 D, Aqueous coating, Physical parameters, Kinetics of drug release &#x0D; &#x0D; Bangladesh J. Sci. Ind. Res. 42(3), 239-248, 2007

Effects of Plastic and Acrylate Polymers on the Release Profile of Ambroxol Hydrochloride Controlled Release Pellets

The effects of Ammonio Methacrylate copolymer dispersion (Eudragit® NE 30 D) and Polyvinyl Acetate dispersion (Kollicoat® SR 30 D) are compared on the in vitro release of Ambroxol Hydrochloride from coated pellets in the current study. The nuclei pellets were manufactured by Extrusion-Spheronization with the drug, microcrystalline cellulose, lactose, maize starch, and hydroxypropyl methylcellulose followed by fluid bed coating. Dissolution study of coated pellets was performed with USP Type-II apparatus in acidic (0.1N HCl for 1 h) and buffer (phosphate buffer, pH 6.8 for 11 h) media to simulate gastrointestinal environment. The release profile of drug from two types of polymers were distinct and drug release was sustained longer by Polyvinyl Acetate film than Acrylate polymer. Key words: Aqueous coating, Eudragit® NE 30D, Kollicoat® SR 30D, release kinetics, pellets, extrusion-spheronization doi: 10.3329/dujps.v7i2.2176 Dhaka Univ. J. Pharm. Sci. 7(2): 181-186, 2008 (December)

&lt;i&gt;In vitro&lt;/i&gt; Release Kinetics Study of Diclofenac Sodium from Acrylic Polymer Coated Pellets

The aim of the present study is to investigate the effect of Ammonio Methacrylate Copolymer Type B (Eudragit RS 30 D) on the release kinetics study of diclofenac sodium form coated pellets. The effect of the incorporation of xanthan gum into the coating formulation was also the goal of this study. Eudragit RS 30 D and xanthan gum was added into the formulation at 5:1 ratio. Different percent of this polymeric combination was loaded on to the drug-loaded pellets. It was found that the cumulative % release of drug decreased with the increase of polymer load in all cases. From all formulations it was observed that the release of diclofenac sodium in 0.1N HCl media was very low (maximum 3.5%) at first 2 hours. Better sustaining effect was found from Eudragit RS 30 D and xanthan gum combinations. Drug was released linearly along with time throughout the whole dissolution process in phosphate buffer (pH 6.8) and it was also revealed that, in all cases the release of diclofenac sodium followed mixed release kinetics but zero order release kinetics predominates. &#x0D; &#x0D; Key words: Diclofenac sodium, pellets, sustained release, in vitro, kinetic analysis. &#x0D; &#x0D; Dhaka Univ. J. Pharm. Sci. 6(1): 1-7, 2007 (June)&#x0D; &#x0D; The full text is of this article is available at the Dhaka Univ. J. Pharm. Sci. website