Eudragit NE Research Articles

Transdermal Drug Delivery System of Haloperidol to Overcome Self-Induced Extrapyramidal Syndrome

Haloperidol (HAL), an antipsychotic, is associated with side effects of drug-induced extrapyramidal syndrome (EPS) in conventional monotherapy. Controlled released transdermal dosage form (TDDS) of the drug was designed for maintenance therapy. Matrix-diffusion type transdermal film of HAL was designed with Eudragit NE 30D copolymer without permeation enhancer in different combinations. For the feasibility studies, all standard evaluations were performed, and their results pointed toward the suitability of TDDS. The drug release and permeation studies in Franz diffusion cell in 20% PEG-normal saline followed the Higuchi equation with optimum correlation coefficient. The neuroleptic efficacy was confirmed by maximum graded response in a rotarod apparatus. The neuroleptic-induced catatonia (EPS) in albino rats was minimum with a score of zero over a 72-hr study. The pharmacokinetic parameters in rabbit model showed a very significant prolongation of action up to 72 hr with steady-state plasma concentration (cpss) of 11.58 ng/mL. Thus, the HAL-loaded TDDS improved the therapeutic profile by preventing the neuroleptic-induced EPS and might be a better alternative during its long period of psychiatric treatment over conventional dosage form.

Influence of Eudragit® NE 30 D Blended with Eudragit® L 30 D-55 on the Release of Phenylpropanolamine Hydrochloride from Coated Pellets

The objective of this study was to investigate the influence of Eudragit® NE 30 D blended with Eudragit® L 30 D-55 on the release of phenylpropanolamine hydrochloride (PPA·HCl) from coated pellets. The miscibility of Eudragit NE 30 D/L 30 D-55 blends at different ratios was studied by using differential scanning calorimetry. The release of PPA·HCl from pellets coated with Eudragit NE 30 D alone and a Eudragit NE 30 D/L 30 D-55 blend, when stored at 40°C and 60°C, was determined by UV spectroscopy. Eudragit NE 30 D and Eudragit L 30 D-55 were miscible in ratios greater than 4:1. The curing time that was required to reach an equilibrium state decreased with the addition of Eudragit L 30 D-55. The presence of Eudragit L 30 D-55 also produced a film coating that was less tacky, and a dispersion of Eudragit NE 30 D containing Eudragit L 30 D-55 (5:1) was shown to prevent agglomeration of the pellets during coating and storage.

Matrix formation in sustained release tablets: possible mechanism of dose dumping

Conditions under which poly(ethyl acrylate, methyl methacrylate) 2:1 (poly(EA-MMA), Eudragit NE) forms a stable matrix were investigated in tablets with diclofenac sodium (DS) as an active substance. DS was granulated with the aqueous polymer dispersion. Granules and/or tablets were cured under various temperature and humidity conditions. A six position rotating disk (200 rpm) apparatus was used for the release studies conducted in 37 °C acid then phosphate buffer (0.4 M) pH 6.8 or buffer only as the dissolution media. Morphological characteristics of the tablet surface were observed under SEM. Changes in tablet structure upon curing were evaluated through changes in tablet mechanical characteristics. Modulus of rupture, Young's modulus, AUC, AUC <max, AUC >max, where AUC=AUC <max+AUC >max, were determined by the three-point bending test. Some poorly cured tablets dose-dumped when placed directly into buffer but not if first placed in acid and then buffer. A higher content of polymer in the matrix, led to formation of a stronger polymer network upon higher curing temperature and/or longer curing duration, whereas relative humidity had a minor effect.

Self-adhesive thin films for topical delivery of 5-aminolevulinic acid

Self-adhesive thin-films have been developed as a topical delivery system for 5-aminolevulinic acid (ALA). The thin films are suitable for use during the photodynamic therapy of epithelial skin tumors. They are composed of a combination of the lipophilic polymer Eudragit NE and the lipophilic plasticiser acetyl tributyl citrate (ATBC). Because of its hydrophilicity, ALA forms suspension systems within these thin films, as evidenced by light microscopy. ALA release measured using Franz cells is very rapid from a Eudragit NE thin film loaded with 10% w/w ALA (200 μg ALA after 2.5 h), and even higher when ATBC is included. A Eudragit NE/ATBC (1: 2) thin film loaded with 20% w/w ALA releases 2000 μg ALA after 3.5 h. Combined release/permeation of ALA through excised membranes of human stratum corneum plus epidermis yielded fluxes of 50–100 μg ALA within 5 h for the Eudragit NE/ATBC (1: 2) thin film. The ATBC acts as a permeation enhancer for ALA. Scanning electron microscopy of the thin film surface shows protruding ALA particles which rapidly dissolve on contact with an aqueous medium. This surface dissolution mechanism is the cause of the rapid ALA release and hence also the high skin permeation in vitro. The mechanical properties of the thin films were also briefly examined. Adhesive strength increases with higher ATBC loading and decreases with higher ALA loading. Internal cohesion decreases with greater ATBC loading and increases with higher ALA loading. As part of this project, an improved derivatisation assay for gradient HPLC of ALA with 9Fluorenylmethyloxycarbonylchloride is also presented.

Development of local patches containing melilot extract and ex vivo–in vivo evaluation of skin permeation

Melilot extract could be effective in treating localised varicose syndrome or capillary fragility. The monolayer patch was selected to obtain a prolonged release of coumarin contained in the phytocomplex. Two types of methacrylic patches (patch 1 based on a blend of Eudragit E100 and Eudragit NE; patch 2 based on Eudragit L100) were prepared. Both patches were equivalent in terms of coumarin release and ex vivo skin permeation profiles. The two patches differed significantly as regards respective adhesive properties. At low peel rate only patch 1 showed adhesive failure as confirmed by the in vivo performance. When comparing the behaviour of the patches containing melilot extract with analogous patches containing synthetic coumarin, no melilot phytocomplex enhancer effect was shown. The data of the ex vivo coumarin skin permeation and those obtained by the in vivo stripping technique showed a good correlation ( r 2=0.9727 for patch 1, r 2=0.9835 for patch 2).

Tableting of coated ketoprofen pellets

Ketoprofen pellets were prepared by the method of extrusion-spheronization, and a film coating of guar gum and Eudragit NE was applied to drug cores using pan technology. In an attempt to design a tablet which, on peroral administration, disintegrates rapidly, releasing intact coated pellets which maintain the integrity of both the cores and their release retarding membrane, Avicel PH101, lactose DT and magnesium stearate were used as excipients to prepare tablets comprising ketoprofen pellets or microcapsules. Preliminary experiments were conducted on uncoated pellets to determine the optimum compression force required to prepare tablets of satisfactory mechanical properties and release profiles. Coated pellets containing ketoprofen were used to investigate the influence of excipients levels. In an attempt to minimize problems associated with blending and segregation of microcapsules and excipients, placebo spheres of Avicel PH101 and lactose DT were produced by the method of extrusionspheronization. The use of placebo spheres produced tablets with improved drug content uniformity and disintegration time. The tensile strength of such compacts was enhanced by excluding magnesium stearate from the mixes without significant problems of sticking or picking. The use of placebo pellets resulted in significant damage to drug microcapsules, which was attributed to the higher hardness and density of the excipients pellets. The role of membrane coating in protecting the drug core during compression was also evaluated.

Sustained release properties of alginate microspheres and tabletted microspheres of diclofenac sodium

This study focused on the properties of diclofenac sodium (DNa) alginate (alg) microspheres and tabletted DNa alg microspheres using different polymers as additives. DNa alginate microspheres were prepared by the emulsification method and different polymers such as Eudragit (Eud) NE 30 D, Eudragit (Eud) RS 30 D and Aquacoat, which were incorporated into alg gel to control the release rate of drug. The release properties of DNa alg microspheres (1:1) were affected by the size, drug load of microspheres and also by the incorporated polymers, pH and ionic strength of dissolution medium. Tabletting of alg microspheres using carrageenan (carr), alg, pectin, NaCMC, tragacanth (trgh) and HPMC as additives in a (50:50) ratio produced tablets with good physical properties and also better controlled release of DNa. Dissolution studies were carried out in pH7.2 phosphate buffer and phosphate buffers whose pH values were gradually changed from pH 3 to 7.4. The rank order of DNa release from tablets was carr<alg<pectin<NaCMC<trgh<HPMC which relates to the viscosity and swelling properties of polymers. The drug release was very slow from trgh and HPMC based tablets, but addition of carr or alg in different ratios could adjust the release rate of drug.

Studies on controlled release dimenhydrinate from matrix tablet formulations

In this study, controlled release dosage forms of dimenhydrinate were prepared with different polymers as MC, HEC, Carbopol 934, Eudragit RLPM and Eudragit NE 30 D at different concentrations (2.5–10%). Direct compression (DC) and wet granulation (WG) techniques were used to prepare the tablets. Magnesium stearate was the lubricant while starch gel was the binder. For the quality control of tablets prepared according to 11 different formulations, weight deviation, hardness, friability, diameter–height ratio, content uniformity of the active substance and in vitro dissolution techniques were performed. Dissolution rate of these tablets was controlled by USP XXII dissolution method and the profile of each tablet was plotted and only for F 5 was evaluated kinetically.

Dermal Patches for the Controlled Release of Miconazole: Influence of the Drug Concentration on the Technological Characteristics

The aim of this work was to evaluate the effect of different amounts of miconazole nitrate (MIC) on the technological characteristics (drug release profile, adhesiveness, and water vapor permeability) of a nonocclusive dermal therapeutic system (DTS) for the treatment of tinea unguium infection. Artificial silk was used as a backing layer. The self-adhesive matrix was made of a mixture of Plastoid® E 35 L (PL L), an adhesive hydrophilic polymer, and Eudragit® NE 40 D (EU NE), a nonadhesive hydrophobic polymer able to modify the drug release. Plastoid E 35 L is a copolymer of dimethylaminoethyl methacrylate and neutral methacrylic ester. Eudragit NE 40 D is a copolymer of ethylacrylate and methylmethacrylate. Formulations containing different amounts of MIC, ranging from 2% to 16% w/w of the dried matrix, were designed. Drug crystals were observed by polarizing light microscopy, proving the incomplete solubilization of MIC only in the matrices containing 8% w/w or more of this compound. All systems provided an in vitro control of drug release for at least 24 hr. The amount of the drug released increased with drug loading in all DTS. The percentage of the drug released was the same in all the DTS containing detectable crystals of MIC. When the MIC was completely dissolved in the matrix, the released percentage decreased when drug loading increased. The water vapor permeability and the adhesive properties of the DTS were excellent.

Feasibility of an In Vitro Microbiological Model as an Alternative to the Rabbit Eye Model

Ocular inserts of gentamicin sulfate with polyvinyl alcohol (PVA) 1.5%, 2.0%, and 2.5% and a combination of methyl cellulose 2% and Eudragit NE 30D 30%, 35%, and 40% w/w of methyl cellulose were fabricated by a casting technique. The inserts were sterilized by gamma radiation at 25 kGy and tested for sterility. The microbiological efficacy of the ocular inserts against Staphylococcus aureus ATCC 6538P and Pseudomonas aeruginosa NCIM 2200 was evaluated by developing an in vitro microbiological model and an in vivo noninvasive rabbit eye model. Parameters of the in vitro microbiological model were varied, and the results correlated with a noninvasive rabbit eye model. The in vitro model proved to be a viable alternative to the rabbit eye model in evaluating the microbiological efficacy of gentamicin sulfate ocular inserts.

In Vitro Release Study of Transdermal Delivery Systems of Progesterone

A potential transdermal application of progesterone was investigated. In vitro diffusion studies of the drug were performed. Investigations were carried out in order to examine if the addition of urea, pantothenol, or laurocapram can enhance the release rates from Eud (Eudragit NE 30 D) matrices. Pantothenol and urea increased the release 1.4- to 1.6-fold. The transdermal therapeutic system (TTS) containing 10% laurocapram delivered the highest release rates with a 2.8-fold enhancement.

Influence of buffer solution composition on drug release from pellets coated with neutral and quaternary acrylic polymers and on swelling of free polymer films

Aqueous dispersions of the acrylic resins poly(ethylacrylate-methylmethacrylate-trimethylammonioethyl methacrylate chloride) (quaternary PMMA, Eudragit RS30D) and poly(ethylacrylate-methylmethacrylate) (neutral PMMA, Eudragit NE30D) were used to cast free films and to coat theophylline pellets. The release of theophylline from pellets coated with Eudragit RS showed a great dependence on the composition of the buffer solution. The highest release rates were observed in formate buffers; they were intermediate in phosphate buffers and low in citrate buffers and in all buffers containing chloride ions. The rates of release correspond with the extent of swelling of free Eudragit RS films, measured as weight gain in the respective solutions; a high water content in the swollen film lead to a fast release. However, the extent of ion exchange between the chloride ions of the polymer and the anions of the buffer solutions was of the same order of magnitude. In contrast, the release of theophylline from pellets coated with Eudragit NE and the swelling of free Eudragit NE films was not significantly affected by the composition of the buffer solutions.

An Organic Acid-Induced Sigmoidal Release System for Oral Controlled-Release Preparations. 2. Permeability Enhancement of Eudragit RS Coating Led by the Physicochemical Interactions with Organic Acid

The drug release mechanism of the sigmoidal release system (SRS), which is a newly developed multiple-unit type time-controlled release system, was investigated. The drug release rate from the Eudragit RS-coated theophylline beads was considerably enhanced in succinic acid aqueous solution compared with the release rate in water. However, the drug release rate from the beads coated with Eudragit NE 30D, which has no quaternary ammonium groups in the polymer chain, was not affected by succinic acid, suggesting that the quaternary ammonium groups of Eudragit RS are essential to produce the unique drug release profile of the SRS. Ion-exchange experiments revealed that organic acids could interact with Eudragit RS by an ion exchanging mode to various extents depending on the acid species. To examine the individual effect of dissociated and undissociated forms of succinic acid on the drug release behavior of the Eudragit RS-coated theophylline beads, dissolution studies were performed in succinic acid or monosodium succinate aqueous solutions with various concentrations. The drug release rate was found to change depending on the concentration of either the dissociated or the undissociated form of succinic acid with different concentration dependency. From the glass transition temperature measurement using Eudragit RS cast film, it was assumed that the undissociated succinic acid was distributed to the hydrophobic segment of the polymer, resulting in the increase in mechanical flexibility of the film; whereas the dissociated succinic acid electrostatically interacted with the quaternary ammonium groups of the polymer to promote the distribution and to create new ionic circumstances: both effects of the organic acid can accelerate the hydration of Eudragit RS film. All these results suggest that the unique S-shaped drug release profile of SRS can be brought about by a drastic increase in the permeability through the hydration of Eudragit RS-based coating during the drug release process.

Water vapour permeation of aqueous based ethylacrylate methylmethacrylate copolymer films

The water vapour permeation rate of isolated films consisting of Eudragit NE 30 D was found to be dependent on the film composition, film thickness, isolation technique and thermal treatment. The temperature during the experiments appeared to influence dramatically the water vapour permeation rate. With increasing temperature, the water permeation rate of the film increased. It was shown that Fick's law was not obeyed for water vapour permeation of aqueous based Eudragit NE 30 D films, indicating that investigating different film compositions at one thickness leads to erroneous conclusions.

Evaluation of drug-containing polymer films prepared from aqueous latexes.

Polymeric films containing salicylic acid or propranolol HCl were prepared by casting and drying a drug-containing, aqueous colloidal polymer dispersion (Eudragit NE 30D) as an alternative to films cast from organic polymer solutions. The drug was either dissolved (salicylic acid) or dissolved/dispersed (propranolol HCl) in the polymeric matrix. Incompatibilities (flocculation or coagulation) between salts of basic drugs and two ethylcellulose latexes were overcome by substituting the anionic surfactants with a nonionic surfactant (Pluronic P103). The drug release was studied as a function of drug loading, film thickness, amount of hydrophilic additive (hydroxypropyl methylcellulose), and storage humidity. The release of propranolol HCl (monolithic dispersion) was a combination of diffusion through the polymer and pores or channels; the extent of each release mechanism depended on the drug loading. On DSC thermograms, melting transitions were obtained with monolithic dispersions but not with monolithic solutions. The heat of fusion was linearly correlated to the amount of drug in the films. The amount of drug remaining in the film after the dissolution study was not detectable and corresponded to the drug dissolved in the polymer. The drug release increased with increased drug loading and increased amount of hydroxypropyl methylcellulose but was independent of film thickness and relatively insensitive to different storage humidities.

Preparation and Evaluation of &lt;i&gt;In Vitro&lt;/i&gt; Release Kinetics of Theophylline Loaded Matrix Tablet Based on Eudragit NE 30 D and Eudragit RS 30 D

In the present study efficiency of Eudragit NE 30 D and RS 30 D as matrix forming materials was investigated. It was found that theophylline loaded granules prepared with these two polymers could not sustain drug release for a significant period of time. However, compression of these granules into tablets retarded drug release for up to 7 hours. Release was similar with both of the polymers. Effects of fillers and rate modifiers on drug release have been assessed. Incorporation of lactose and starch caused substantial release of theophylline from both the polymeric systems. Avicel PH 101 intensified the retardation effect of both NE 30 D and RS 30 D on theophylline release. Hydrophobic excipients also show retardation of release from both NE 30 D and RS 30 D. Key words: Eudragit RS 30 D; Eudragit NE 30 D; Theophylline; Matrix system; Controlled release DOI: 10.3329/dujps.v8i2.6030 Dhaka Univ. J. Pharm. Sci. 8(2): 153-159, 2009 (December)