Eudragit NE Research Articles

Development of Novel Tamsulosin Pellet-Loaded Oral Disintegrating Tablet Bioequivalent to Commercial Capsule in Beagle Dogs Using Microcrystalline Cellulose and Mannitol.

In this study, we developed a tamsulosin pellet-loaded orally disintegrating tablet (ODT) that is bioequivalent to commercially available products and has improved patient compliance using microcrystalline cellulose (MCC) and mannitol. Utilizing the fluid bed technique, the drug, sustained release (SR) layer, and enteric layer were sequentially prepared by coating MCC pellets with the drug, HPMC, Kollicoat, and a mixture of Eudragit L and Eudragit NE, respectively, resulting in the production of tamsulosin pellets. The tamsulosin pellet, composed of the MCC pellet, drug layer, SR layer, and enteric layer at a weight ratio of 20:0.8:4.95:6.41, was selected because its dissolution was equivalent to that of the commercial capsule. Tamsulosin pellet-loaded ODTs were prepared using tamsulosin pellets and various co-processed excipients. The tamsulosin pellet-loaded ODT composed of tamsulosin pellets, mannitol-MCC mixture, silicon dioxide, and magnesium stearate at a weight ratio of 32.16:161.84:4.0:2.0 gave the best protective effect on the coating process and a dissolution profile similar to that of the commercial capsule. Finally, no significant differences in beagle dogs were observed in pharmacokinetic parameters, suggesting that they were bioequivalent. In conclusion, tamsulosin pellet-loaded ODTs could be a potential alternative to commercial capsules, improving patient compliance.

Design and development of transdermal drug delivery systems of metoprolol succinate

Introduction: Most of the drugs taken orally are found to be not as effective as desired. To overcome such problems transdermal drug delivery system has been developed. Transdermal drug delivery systems (TDDS) are dosage forms which involve in the drug transport to viable epidermal and or dermal tissues of the skin for local therapeutic effect while a very major fraction of drug is transported into the systemic blood circulation. Several important advantages of transdermal drug delivery are limitation of hepatic first pass metabolism, enhancement of therapeutic efficacy and maintenance of steady plasma level of the drug. Materials and Methods: The current research work includes the development of Metoprolol succinate transdermal patches and their evaluation. The transdermal patches were formulated by solvent casting method varying the concentrations of Eudragit NE 30D (%v/w) and DMSO (%w/w of dry polymer). Results: Among the nine formulations of the transdermal patches F3 formulation was considered as the optimized formulation considering its tensile strength, percentage elongation, percentage drug content and mainly cumulative percentage drug diffusion. The cumulative percentage drug diffused from F3 formulation was found to be 97.36 at the end of 24th hour. Conclusion: Stable and effective transdermal drug delivery systems of metoprolol succinate for once daily administration were prepared for better patient compliance. Keywords: Transdermal drug delivery, Solvent casting method, Metoprolol succinate, Ttherapeutic efficacy, Steady plasma level.

FORMULATION DEVELOPMENT OF COLON TARGETED MESALAMINE PELLETS: IN VITRO-IN VIVO RELEASE STUDY

Objective: This study was intended to investigate the potential of the colon specificity approach comprising of use of pH-sensitive and time-dependent polymers in combination for precise colonic release of Mesalamine or 5-Aminosalicylic acid (5-ASA).
 Methods: The extrusion and spheronization method, preferably employed in industry for allowing high dose capacity to formulate, was used to prepare drug pellets. The Wurster coating technique used for aqueous coatings of Eudragit NE 40D as an inner coat and Eudragit FS30D as outer coat. The changing pH media used for in vitro release study of optimization batches for both the coating levels. A scanning electron microscope (SEM) was used to evaluate coating thickness and surface morphology.
 Results: The pharmacokinetic parameters of formulation evaluated by in vivo study in rabbits revealed that the uncoated formulation released the drug too early in the gastrointestinal tract (GIT) with a mean Cmax of 1205.28±0.37 µg/ml at 2 h after administration, whereas desired lag time was achieved in case of coated pellets exhibiting mean Cmax 465.94±0.21 µg/ml and tmax of 8 h.
 Conclusion: The in vitro and in vivo release study divulge the reliability of approach involving the use of pH sensitivity and time dependency of polymer for drug release in a single formulation for the treatment of colonic diseases. Hence, the present study provides constructive results for colon targeting of 5-ASA pellets with industrially feasible processes.

Development and evaluation of topical films containing phytoestrogenic diaryheptanoids from Curcuma comosa extract

Rational: Phytoestrogens have been found to delay signs of skin aging in post-menopausal women, in a way similar to the effects of estrogens. Diarylheptanoids from a rhizome of traditional Thai herb named Curcuma comosa is considered to be a novel class of phytoestrogens.Objectives: The aims of this study were to prepare effective topical films using mixed types and vary ratios of hydrophobic (Eudragit RL, Eudragit RS, and Eudragit NE) and hydrophilic polymer (hydroxylpropyl methycellulose, HPMC) with Transcutol as a permeation enhancer for delivery of diarylheptanoids to improve signs of skin aging in post-menopausal women.Material and methods: Topical films were characterized for their physical and mechanical properties. In vitro release, skin permeation and accumulation were evaluated using Franz diffusion cell and the concentrations of diarylheptanoids were determined using high-performance liquid chromatography.Results: The combined formulations between HPMC and Eudragit NE showed the satisfactory physical and mechanical properties, and also provided the highest amount of drug released compared to Eudragit RL and Eudragit RS. When the proportion of HPMC amount in the polymer matrix increased, the cumulative drug release also increased (HPMC: Eudragit NE 6:4 > 5:5 > 4:6). Moreover, they provided a high accumulation of diarylheptanoids within skin when using transcutol as a permeation enhancer.Conclusion: The obtained data provided the skin permeation and accumulation behavior of diarylheptanoids, indicating the feasibility of a skin delivery of the C. comosa extract. The developed films might be topically used as an alternative therapy for protection of skin aging in peri and post-menopausal women.

FORMULATION, DEVELOPMENT AND OPTIMIZATION OF MODIFIED RELEASING PELLETS OF DRUG CARVEDILOL

The main objectives of present work was to design and evaluate modified releasing pellets of drug, Carvedilol, inrespect to increase patient compliance and therapeutically benefits. The modified releasing pellets were made by thesub-coating with sodium bicarbonate and hydroxyl propyl methyl cellulose which was utilized to keep the spheres instomach for long time. To get modified release of active pharmaceutical ingredients from the pelletizing process, theywere coated with methacrylic acid co-polymer (Eudragit NE 40D). Hence sodium bicarbonate, hydroxyl propylmethyl cellulose and eudragit NE 40D are the key ingredients of this dissertation work. Concentration of sodiumbicarbonate, hydroxyl propyl methyl cellulose and eudragit NE 40D in coating suspension was optimized by initialstudies and factorial design. The procedure based optimization analysis also perform to optimize process factors likeproduct temperature and spraying rate to improve physical parameters and micromeritic characteristics of spheres bypreliminary data.

Use of acoustic levitation to examine the drying behavior of microdroplets of polymer latex dispersions

An acoustic levitator was used to determine the drying kinetics and behavior of microdroplets of colloidal polymer latex dispersions. It was possible to measure the kinetic behavior of evaporation rate, droplet surface temperature, and droplet/particle aspect ratio for two polymers at two different volume fractions of dispersed phase, ϕint. A drying air temperature of 60 °C, a relative humidity of 1 %, and a flow rate of 0.5 L/min through the levitator chamber were used. Under these conditions Eudragit NE 30 D was dried above its minimum film-forming temperature and a critical point of drying could be detected from sharp changes in surface temperature and droplet/particle shape. The drying rate depended inversely on ϕint which increases continually during drying. Aquacoat was dried below its minimum film-formation temperature, and a two-step change in particle/droplet shape and surface temperature was observed. Although the nanoparticles of Aquacoat form an interfacial film at the first step, this does not substantially reduce drying rate. Only the second step change in surface temperature was accompanied by a decrease in drying rate as the surface film is now sufficiently condensed but not fused. The levitator detects therefore a differentiated picture of the changes taking place in drying rate, surface temperature, and droplet/particle.

Development of metoprolol tartrate-loaded sustained-release pellets: effect of talc on the mechanism of drug release

Talc is one of the most commonly used antiadherents in the coating film. However, the mechanism of influence of talc on drug release has yet to be fully understood. In this study, metoprolol tartrate (MT)-loaded Eudragit NE 30 D-coated sustained-release (SR) pellets were prepared using talc as an antiadherent in the layering and coating processes. Talc significantly reduced the stickiness of the layered or coated substrates, thus enhancing the process smoothness. Moreover, the incorporation of talc into the coating film significantly affected drug release. The water vapor permeability and drug permeability of free films increased as the concentration of talc increased. Importantly, talc had a dynamic effect on the drug release. The drug release rate of the pellets in the initial stage (within 2 h) increased with increasing talc concentrations, which exceeded the critical pigment volume concentration resulted in leaks formation in the coated film. However, subsequent swelling of the membrane and expansion of the copolymer network eliminated the influence of talc and the drug release was then controlled by the polymeric membrane. These results suggest that talc contributed to the reduction of the sticking of layered or coated substrates, and facilitated the manufacturing process and drug release properties.

A method for the preparation of sustained release-coated Metoprolol Succinate pellet-containing tablets

The purpose of this study was to develop a method to prepare Metoprolol Succinate (MS) sustained release pellets and compress them into pellet-containing tablets without losing sustained release property. The drug layered pellets were coated with Eudragit NE 30D to obtain a sustained release (SR) property. The mechanical properties and permeability of the coating film were tailored by adjusting the proportion of talc in the coating dispersion and the weight gain of the coating film. Pellets with different MS release rates were tested and then mixed together by different ratios to optimize drug release rate. The mixed pellets were compressed into tablets with cushioning excipients. The results showed that when the ratio of talc and coating material was 1:4, the coating operation could be conducted successfully without pellet conglutination and the mechanical property of the coating film was enhanced to withstand the compress force during tableting. Blending SR-coated pellets of 20% weight gain with SR-coated pellets of 40% weight gain at the ratio of 1:5 could produce a constant and desired drug release rate. The formulation and the procedure developed in the study were suitable to prepare MS pellet-containing tablets with selected SR properties.

Characterizations of plasticized polymeric film coatings for preparing multiple-unit floating drug delivery systems (muFDDSs) with controlled-release characteristics.

Effervescent multiple-unit floating drug delivery systems (muFDDSs) consisting of drug (lorsartan)- and effervescent (sodium bicarbonate)-containing pellets were characterized in this study. The mechanical properties (stress and strain at rupture, Young’s modulus, and toughness) of these plasticized polymeric films of acrylic (Eudragit RS, RL, and NE) and cellulosic materials (ethyl cellulose (EC), and Surelease) were examined by a dynamic mechanical analyzer. Results demonstrated that polymeric films prepared from Surelease and EC were brittle with less elongation compared to acrylic films. Eudragit NE films were very flexible in both the dry and wet states. Because plasticizer leached from polymeric films during exposure to the aqueous medium, plasticization of wet Eudragit RS and RL films with 15% triethyl citrate (TEC) or diethyl phthalate (DEP) resulted in less elongation. DEP might be the plasticizer of choice among the plasticizers examined in this study for Eudragit RL to provide muFDDSs with a short time for all pellets to float (TPF) and a longer period of floating. Eudragit RL and RS at a 1∶1 ratio plasticized with 15% DEP were optimally selected as the coating membrane for the floating system. Although the release of losartan from the pellets was still too fast as a result of losartan being freely soluble in water, muFDDSs coated with Eudragit RL and RS at a 1∶1 ratio might have potential use for the sustained release of water-insoluble or the un-ionized form of drugs from gastroretentive drug delivery systems.

Transdermal films containing tizanidine: in vitro and in vivo evaluation

Myogenic pain and spasticity are of most important symptoms that occupy clinician's thinking in order to relief of discomfort associated with acute, painful disorders of skeletal muscles. Oral tizanidine hydrochloride (THCl) suffers from extensive hepatic first pass effect and hence low bioavailability. The purpose of the present study was to develop bioadhesive transdermal delivery systems of THCl using some of Eudragit polymers and chitosan in order to optimize its release profile, and the overall clinical performance. The prepared formulae were subjected to physicochemical examination, in vitro release, in vitro skin permeation studies, stability studies and in vivo studies. It was observed that Higuchi diffusion model was the best fitted model for the release of the drug from the tested films. The results obtained were promising, with (Eudragit NE 30D: Eudragit R 100, ENE: ERL (2:1)) film showing the most satisfactory combined physicochemical, in vitro, stability and in vivo studies.

A novel gastro-floating multiparticulate system for dipyridamole (DIP) based on a porous and low-density matrix core: In vitro and in vivo evaluation

The study was aimed to develop a novel gastro-floating multiparticulate system based on a porous and low-density matrix core with excellent floatability. The gastro-floating pellets (GFP) were composed of a porous matrix core, a drug loaded layer (DIP and HPMC), a sub-coating layer (HPMC) and a retarding layer (Eudragit(®) NE 30D). The porous matrix cores were evaluated in specific. EC was chosen as the matrix membrane for its rigidity and minimal expansion to large extent. The porous matrix core was achieved by the complete release of the bulk water soluble excipient from the EC coated beads, and mannitol was selected as the optimal water soluble excipient. SEM photomicrographs confirmed the structure of porous matrix cores. The compositions of GFP were investigated and optimized by orthogonal array design. The optimized formulation could sustain the drug release for 12h and float on the dissolution medium for at least 12h without lag time to float. The pharmacokinetic study was conducted in beagle dogs, and the relative bioavailability of the test preparation was 193.11±3.43%. In conclusion, the novel gastro-floating pellets can be developed as a promising approach for the gastro-retentive drug delivery systems.

Modified-release capsules containing sodium riboflavin 5′-phosphate

Introduction: The focus of this work was to produce delayed-release capsules containing riboflavin (vitamin B2, as API) layered pellets. Riboflavin therapy is indicated in patients with a riboflavin deficiency, which usually occurs in conjunction with malabsorption, alcoholism or a protein-calorie deficiency and rarely as the sole vitamin deficiency. Riboflavin is readily absorbed from the upper gastrointestinal tract by a specific transport mechanism. The dissolution rate of coated capsules was controlled through the coating of the capsules and the thickness of the coating layer.Methods: The core pellets (Cellet 300) were loaded with a 10% aqueous solution of sodium riboflavin 5′-phosphate by a layering technique in a coating pan. Hard capsules were filled with riboflavin layered pellets and coated with Eudragit NE polymer with different coating layer thicknesses. The dissolution was tested in gastric and intestinal fluids with the half-change method. The dissolution profiles were analyzed with the use of different mathematical models and an attempt was made to predict the optimum coating film thickness that ensures the required degree and rate of dissolution.Results: A new solid dosage form was developed which can enhance the bioavailability of riboflavin. RRSBW distribution and the Chapman–Richards growth function were used to fit the dissolution profiles. Statistical analysis indicated that the best products were described by the Chapman–Richards equation. The results were utilized to create a theoretical model suitable for prediction of the optimum film thickness that ensures the required release of riboflavin.

Preparing of pellets by extrusion/spheronization using different types of equipment and process conditions

Introduction: The focus of this work was to produce matrix pellets made by extrusion/ spheronization using two types of equipment. The aim was to accomplish the laboratory-scale I process that has been already optimized and accepted with another type of equipment (laboratory-scale II).Methods: A matrix pellet formulation consisting of MCC, Eudragit NE 30D and diclofenac sodium was used in the two types of equipment. Physico-chemical parameters and the dissolution profiles of the pellets in phosphate buffer pH 6.8 were compared.Results: Pellets from both processes were similar in shape and tensile strength. They differed in particle size and dissolution profile. This may be contributed to different spheronization conditions.

Polymeric coatings for a multiple-unit pulsatile delivery system: Preliminary study on free and applied films

In order to adapt a previously described swellable/erodible pulsatile delivery system to a multiple-unit configuration, insoluble films with adequate permeability and flexibility were proposed for application to its functional hydroxypropyl methylcellulose (HPMC) layer. By slowing down the penetration of water into the system, such films would be expected to improve the relevant effectiveness in delaying the onset of release without possibly impacting on the mechanism involved. Free films of Eudragit(®)NE containing differing amounts (10-20%) of a superdisintegrant, i.e. Explotab(®)V17, Ac-Di-Sol(®), Kollidon(®)CL or Kollidon(®)CL-M, were prepared by spraying technique and evaluated for hydration, permeability and tensile properties. The hydration and permeability characteristics were enhanced by the addition of the superdisintegrants, generally as a function of their concentration. Explotab(®)V17 was shown particularly useful to increase the film permeability. Moreover, it exerted a minor impact on the advantageous tensile properties of the acrylic polymer, especially in the wet state. Based on these results and on a preliminary release study performed with two-layer devices, the Eudragit(®)NE film with Explotab(®)V17 at the highest investigated percentage was identified as a potential formulation candidate for being applied to HPMC-coated cores thus allowing the onset of release to effectively be delayed by coatings of reduced thickness.

Optimization of metoprolol tartrate modified- release matrix tablet formulation using Eudragit NE as binder for metoprolol fluid bed granulation

The aim of this experimental work was to investigate the possibility of obtaining hydroxypropyl methylcellulose (HPMC) hydrophilic matrix extended-release dosage forms with metoprolol by using aqueous dispersions of Eudragit NE, as binders in fluid bed granulation. To evaluate the influence of formulation variables (levels of HPMC—Methocel K100 M and Surelease E7 19010) on drug release during a period of time of 12 hours, and on the kinetic release, a full factorial experimental design with two factors and three levels was used. The formulation factors were the granulation polymer concentration and the matrix-forming polymer concentration. The obtained results have shown that the percentage of the drug released during the 12 hours is influenced both by the Methocel ratio and the Eudragit NE ratio; increasing the ratios of Eudragit and Methocel leads to the decrease of the percentage of the released drug.The influence of Eudragit NE percentage is maximum at four and six hours, but the influence of Methocel K100 M concentration is almost the same at all sampling times; all studied formulations showed a kinetic release that fitted best with the Peppas model.

Optimization of metoprolol tartrate modified-release matrix tablet formulation using Eudragit NE as binder for metoprolol fluid bed granulation

Optimization of metoprolol tartrate modified-release matrix tablet formulation using Eudragit NE as binder for metoprolol fluid bed granulation

Optimization of preparation of matrix pellets containing Eudragit® NE 30D

Matrix pellets containing Eudragit NE 30D were produced by extrusion–spheronization, where the critical control points of the process were detected by means of a factorial design. The factors were the quantity of water, the dosing speed, the spheronization speed and the duration of spheronization. The breaking hardness and aspect ratio were measured and the significant factors were determined. On the basis of the results, a new combination of factors was used, which resulted in matrix pellets with the best characteristics.

Drug release mechanisms from Kollicoat SR:Eudragit NE coated pellets

Thin, free films based on Kollicoat SR:Eudragit NE blends were prepared by casting or spraying aqueous dispersions of these polymers, and were thoroughly characterized with respect to their water uptake behavior, water permeability, dry mass loss kinetics, mechanical properties and drug release patterns. A mechanistic mathematical model based on Fick's law of diffusion was used to quantify the experimentally measured release of metoprolol succinate from various types of systems. With increasing Eudragit NE content the films became more hydrophobic, resulting in decreased water permeability as well as water uptake rates and extents. In addition, the dry mass loss upon exposure to the release medium decreased. Consequently, the films’ permeability for the drug decreased. Importantly, metoprolol succinate release from thin films was mainly controlled by pure diffusion, allowing for the determination of the apparent diffusion coefficient of the drug in the different polymeric systems. Knowing these values, drug release from coated pellets could be quantitatively predicted, assuming intact film coatings throughout the observation period. Comparison with independent experimental results showed that crack formation set on very rapidly in the polymeric membranes upon exposure to the release medium in the case of sugar starter cores, irrespective of the polymer:polymer blend ratio and investigated coating level. In contrast, the onset of crack formation was delayed as a function of the blend ratio and coating thickness in the case of microcrystalline cellulose starter cores, attracting less water into the pellets core. The obtained new insight into the underlying drug release mechanisms can be very helpful during device optimization and improve the safety of this type of advanced drug delivery systems.

Drug Transport Mechanisms from Carbopol/Eudragit Verapamil Sustained-Release Tablets

The objectives of this study were to compare dissolution profiles of a verapamil (VRP) formulation manufactured inhouse and Isoptin SR using USP Apparatus 2 and 3 and to elucidate drug release kinetics of these dosage forms. Eudragit NE 30D (ethyl acrylate–methyl methacrylate copolymer in a 2:1 ratio) aqueous dispersion was used as a granulating binder for the manufacture of VRP mini-matrix sustained-release tablets. The wet granulation process was performed to prepare free-flowing granules that were blended with Carbopol. The tablets were manufactured using a single-punch press by compression of the granules with magnesium stearate as a lubricant. Drug release was determined in phosphate buffer solution using USP Apparatus 2 and 3. Dissolution data were fitted to zero- and first-order models; in addition, the kinetic data were determined by evaluation of Higuchi release kinetics. The mechanism of drug release was established using the Korsmeyer–Peppas model. In general, all tablets showed high mechanical resistance with less than 1% friability. There was no significant difference between the dissolution profiles of the formulation manufactured in-house and the commercially available product. The release mechanism of the formulated and marketed products was controlled by anomalous non-Fickian diffusion. VRP release was prolonged for 12 h indicating the usefulness of the formulation as a twice-daily dosage form. The mechanism of drug release for the dosage forms was unaffected by the choice of apparatus.

비글견을 이용한 케토롤락트로메타민 서방형 펠렛 제제의 위궤양 증상 비교와 약물속도론적 평가

Ketrorolac tromethamine (KT), a nonsteroidal anti-inflammatory drug (NSAID) is required repeated administration due to its short blood half-life. To avoid dose-dependent side effects of KT, sustained-release pellets containing KT were prepared by coating with Eudragit RS 100 and Eudragit NE 30D. The in vitro and in vivo drug release behavior of KT from Eudragit RS 100 and NE 30D coated pellet (SR-A), Eudragit RS 100 coated pellet (SR-B) and conventional commercial immediate-release tablet (IR) was investigated. KT from SR-A and SR-B was slowly released over several hours, whereas IR showed rapid initial release in vitro. The pharmacokinetic study in vivo was performed by oral administration in beagle dogs. 5 mg IR was administered 3 times at intervals 5 hr. Five milligrams of IR was administered 3 times at intervals of 5 hr and 15 mg of SR-A and SR-B did once. After administering IR, KT concentration in blood showed high peak- trough fluctuation and stomach ulcer were discovered. On the other hand, SR-A and SR-B sustainedly released KT and reduced the occurrence of stomach ulcer. There sustained-release pellets will be effective system to minimize dosedependent of side effect and improve patient compliance.