Ratio Of Eudragit Research Articles

Effect of Eudragit® NE 40D on The Properties of Pectin Film-Based Polymer Blends

In this work, pectin was used as the primary polymer component while Eudragit® NE 40D was used as polymer blending for the preparation of the thin films. Glycerin was used as a plasticizer. The samples were prepared by a solvent casting method, and their thickness, physicomechanical properties, and moisture ability were characterized. The ratio of Eudragit® NE 40D to pectin was varied to obtain films with tunable mechanical properties and moisture ability. The appearance of the pectin-based blended films was yellowish and transparent by visual observation, and the thicknesses of the pectin-based blended films were in the range of 102–138 µm. The mechanical property of softness of the pectin-based blended films was measured after blending with Eudragit® NE 40D. Thermal stability of pectin-based blended film was also dependent on the amount of Eudragit® NE 40D added; a broadly endothermic and exothermic transition peak were observed. The amorphous state was found in the pectin-based blended films. The cross-sectional morphology of the pectin-based blended films showed a homogeneous film without pores, cracks, or cavities. The moisture content and moisture uptake of the pectin-based blended films were in the range of 18.89–27.52% and 3.38–6.00%, respectively. Overall, the pectin-based blended films showed good properties and these results indicate that pectin-based blended films can potentially be used to prepare thin films for medical and pharmaceutical applications, including drug delivery film dosage forms.

Preparation and Evaluation of Ternary Polymeric Blends for Controlled Release Matrices Containing Weakly Basic Model Drug.

The objective of this study was to evaluate the suitability of a ternary mixture of smart polymers comprised of Eudragit®E100, Eudragit®L100, and sodium alginate to serve as a carrier for sustained drug release for weakly basic drugs. The model drug chosen in this part of the study is Metronidazole. Matrix tablet formulations were prepared by either direct compression or by wet granulation. Dissolution studies were conducted using USP XXΠ rotating paddle apparatus in three different consecutive stages (pH 1.2, 4.8, and 6.8). Tablets made of low to intermediate proportions of sodium alginate and approximately equal proportions of Eudragit®E100 and Eudragit®L100 were found to have a significant modification of drug release rates. Thus, indicating a potential for controlling the drug release for 12 hours depending on polymers ratios in the formulation. The ratio of sodium alginate to total Eudragit® polymers and the ratio of Eudragit®E100 to Eudragit®L100 within the ternary polymeric composition were found critical in determining the controlled release performance. Results of swelling studies were in agreement with the dissolution behaviors of the tablets. The findings suggest the significance of the ternary polymeric compositions in controlling the release of a weakly basic drug, Metronidazole.

Formulation of sustained release bioadhesive minitablets containing solid dispersion of levofloxacin for once daily ocular use

This study aimed to increase ocular residence time of levofloxacin by formulation into zero-order sustained release mucoadhesive minitablets for once daily administration using a hydrophobic–hydrophilic polymeric matrix. Levofloxacin was first formulated into solid dispersion with different ratios of Eudragit® RS then the resulting solid dispersion was mixed with different concentrations of Carbopol® and other excipients to be finally compressed into minitablets. A 24 full factorial design was employed to estimate the effects and interactions of two formulation factors, and to establish their relationships with selected responses in the developed minitablets. The studied factors were: drug to Eudragit® RS ratio, and percent of Carbopol® in the minitablets. Sixteen ocular minitablets formulations were prepared and evaluated for the cumulative percentages drug release at 6, 12, and 24 h, as well as mucoadhesion time, mucoadhesive strength, and swelling index as response variables. After optimizing the responses, the optimized formulation was found to be stable on sterilization using gamma-irradiation and storage at 40 °C/75% RH for six months. In vivo testing of the optimized formulation showed that the minitablets extended levofloxacin release up to 24 h without causing any ocular irritation. The optimized formulation exhibited superior microbiological activity compared to the commercial product.

Dual Component Tablets for the Treatment of Gastroesophageal Reflux Disease

Background and Objective: Gastroesophageal reflux disease (GERD) is one of the most common GIT disorders in which reflux of the GIT contents occurs into the esophagus. The present study is focused on developing a dual component tablet containing a sustained release floating layer of Baclofen and delayed release microspheres of Rabeprazole sodium for the effective treatment of Gastroesophageal Reflux Disease (GERD). </P><P> Methods:Dual component tablets have been developed to achieve a controlled delivery of two different drugs. Microspheres were prepared by the emulsion solvent evaporation method using different ratios of Eudragit S100 and Rabeprazole sodium (3:1, 6:1, 9:1 and 12:1) and optimized using various parameters. Baclofen floating tablets were prepared by the wet granulation method by using different polymers like sodium alginate (S1), pectin (S2) and guar gum (S3) and characterized for their floating properties and in-vitro drug release study. </P><P> Results: The cumulative percentage drug release after 9 hrs was found to be in the range of 46.18 to 65.78% for different microsphere formulations. The result showed that, as the amount of polymer increased, the particle size and % yield were also increased, and drug release and entrapment efficiency were decreased. Among all the formulations, M2 was considered as the best because it showed highest entrapment efficiency. Among baclofen floating tablet formulations, S1 was resulted as optimized formulation because it sustained the drug release up to 8 hrs and showed 64.82±0.82% drug release. Conclusion: From the above optimized formulations bilayer tablets containing floating layer of Baclofen and Rabeprazole sodium loaded microspheres layer were prepared by single-punch tablet machine and evaluated for the weight variation, hardness, thickness, diameter, friability, floating time etc. The results of the study showed that all parameters were within pharmacopoeial limits.

Validated high performance liquid chromatography for simultaneous determination of stability of madecassoside and asiaticoside in film forming polymeric dispersions

The objective of the work was to validate the high performance liquid chromatography for simultaneous determination of stability of madecassoside and asiaticoside in Centella asiatica (L.) Urb., Apiaceae, extract-loaded film forming polymeric dispersions. High performance liquid chromatography method was validated in five topics: linearity and range, limit of detection and limit of quantitation, specificity, precision, and accuracy. Results showed the method had a good linearity (R2>0.9990) in the range of 5–150μg/ml and specific. The limit of detection and limit of quantitation of madecassoside were 81 and 245ng/ml and asiaticoside were 21 and 64ng/ml, respectively. The percent relative standard deviation of intraday and interday precision were less than 1 and 3%, respectively. The accuracy presented as percent recovery was 101.54–103.29% for madecassoside and 100.39–102.58% for asiaticoside. This validated high performance liquid chromatography method was used to determine the stability of the formulation containing Centella asiatica extract. Centella asiatica extract-loaded film forming polymeric dispersions used Eudragit® RS 30D and Eudragit® RL 30D as film former, glycerin as plasticizer, and absolute ethanol as solvent and penetration enhancer. Three formulations with different ratio of Eudragit® RS 30D and Eudragit® RL 30D were prepared and stored for 90 days at 4°C, 25°C, and 40°C. Stability results showed that almost all of the formulations were unstable at 25°C and 40°C. Except, two of three formulations were stable at 4°C. However, the formulation was further developed to improve the stability of madecassoside and asiaticoside in the formulation.

Evaluation of Eudragit® Retard Polymers for the Microencapsulation of Alpha-Lipoic Acid.

Microencapsulation of natural antioxidants in polymeric systems represents a possible strategy for improving the oral bioavailability of compounds that are otherwise poorly soluble. α-lipoic acid (ALA) was microencapsulated with polymethacrylate polymers (blends at various ratios of Eudragit® RS100 and RL100 resins). Microspheres were produced by solvent displacement of an ethanol cosolution of ALA and polymers; the microsuspensions were then freeze-dried, using trehalose as a cryoprotector. Microspheres were characterized in the solid state for micromeritic properties and drug loading, as well as by infrared spectroscopy, powder X-ray diffractometry and differential scanning calorimetry. The antioxidant activity of free and encapsulated ALA was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In vitro release studies, performed in simulated gastric (pH 1.2) and intestinal fluid (pH 6.8), showed that, depending on polymer composition and drug-to-polymer ratio, ALA release can be slowed down, compared to the dissolution pattern of the free drug. Solid-state characterization confirmed the chemical stability of ALA in the microspheres, suggesting that ALA did not develop strong interactions with the polymer and was present in an amorphous or a disordered-crystalline state within the polymer network. As indicated by the DPPH assay, the microencapsulation of ALA in Eudragit® Retard matrices did not alter its antioxidant activity. ALA was effectively encapsulated in Eudragit® Retard matrices, showing a chemical stability up to 6 months at room conditions and at 40°C. Moreover, since the drug maintained its antioxidant activity in vitro, the potential application of these microparticulate systems for oral administration would deserve further studies.

Preparation and stability investigation of tamsulosin hydrochloride sustained release pellets containing acrylic resin polymers with two different techniques

The objective of this study was to prepare tamsulosin hydrochloride-sustained release (TSH-SR) pellets which showed good release stability with frame-controlled method. TSH was added to Eudragit®NE30D and Eudragit®L30D-55 polymers to form drug-loaded inner core. Afterwards, enteric Eudragit®L30D-55 polymer was modified on the surface of it to the final product. Dissolution studies showed that TSH-SR pellets were more stable during the coating process, different curing temperatures and storage conditions compared with TSH pellets produced by film-controlled technique. Appearances and glass transition temperatures (Tgs) of free films and surface morphologies observed by scanning electron microscopy (SEM) of blank sustained release pellets prepared by different ratios of Eudragit®NE30D and Eudragit®L30D-55 further indicated that temperature and relative humidity (RH) were the key factors when Eudragit®NE30D blended with Eudragit®L30D-55 were applied to sustained/controlled release preparations. In addition, SEM identified the surface morphologies of TSH-SR pellets before and after dissolution, which showed intact surface structure and great correlation with release curve respectively.

Formulation studies for mirtazapine orally disintegrating tablets

Objective: Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab).Materials and methods: Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900 mL 0.1 N HCl medium, 900 mL pH 6.8 phosphate buffer or 900 mL pH 4.5 acetate buffer at 37 ± 0.2 °C as dissolution medium.Results: Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media.Discussion: Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles.Conclusion: Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.

Improved oral absorption of exenatide using an original nanoencapsulation and microencapsulation approach

Oral delivery is the most convenient and favorable route for chronic administration of peptides and proteins to patients. However, many obstacles are faced when developing such a delivery route. Nanoparticles (NPs) are among the leading innovative solutions for delivery of these drugs. Exenatide is a peptidic drug administered subcutaneously (SC) twice a day chronically as an add-on therapy for the worldwide pandemic disease, diabetes. Many attempts to develop oral nanocarriers for this drug have been unsuccessful due to the inability to retain this hydrophilic macromolecule under sink conditions or to find a suitable cross-linker which does not harm the chemical integrity of the peptide. In this study, we report about an original oral delivery solution based on a mixture of albumin and dextran NPs cross-linked using sodium trimetaphosphate (STMP). Moreover, we suggest a second defense line of gastro-resistant microparticles (MPs) composed of an appropriate ratio of Eudragit® L100-55 (Eudragit L) and hydroxypropylmethylcellulose (HPMC), for additional protection to these NPs presumably allowing them to be absorbed in the intestine intact. Our results demonstrate that such a system indeed improves the relative oral bioavailability of exenatide to a level of about 77% compared to subcutaneous injection due to the presence of dextran in the coating wall of the NPs which apparently promotes the lymphatic uptake in the enterocytes. This technology may be a milestone on the way to deliver other peptides and proteins orally.

Enhancement of solubility and dissolution of cilostazol by solid dispersion technique.

Cilostazol is practically insoluble in water and thus results in poor bioavailability. Only a few approaches have been reported for improving the bioavailability of cilostazol. Solid dispersion technique via solvent evaporation method was applied to improve the solubility and dissolution of cilostazol. Various polymers, mixture of polymer and surfactant, and mixture of polymers were screened as a carrier for the solid dispersion. Solubility of cilostazol was improved significantly when Eudragit(®) L100 was used as a carrier. However, addition of surfactant to Eudragit(®) L100 decreased the solubility slightly. Whereas, the mixture of Eudragit(®) L100 and Eudragit(®) S100 as a carrier system further increased the solubility. Based on the highest solubility obtained among the carriers screened, 1:1 ratio of Eudragit(®) L100 and Eudragit(®) S100 was selected as a carrier, and drug to carrier ratio was optimized to 1:5. Differential scanning calorimetry and X-ray diffraction studies showed that the characteristic peak of cilostazol disappeared in the solid dispersion, indicating that cilostazol existed in amorphous form in this formulation. Spray drying method was superior to vacuum drying method in terms of dissolution rate. Meanwhile, it was observed that the disintegration rate and the concentration of polymer had some effect on the crystallization of cilostazol in dissolution medium. Tablet formulation containing spray dried solid dispersion showed significant improvement in dissolution as compared to the commercial tablet.

Development of a novel tablet-in-capsule formulation of mesalamine for inflammatory bowel disease

Objective: The objective of the present work was to develop a tablet-in-capsule type of multiunit system, which releases the drug in a controlled manner at pre-programmed time intervals.Methods: The system consists of an enteric-coated hydroxypropyl methylcellulose capsule filled with four units of mesalamine minitablets, each of which was further coated with different ratios of Eudragit® E100 and Eudragit® RS100.Results: In vitro evaluation of tablets coated with Eudragit® E100 and Eudragit® RS100 at different pH conditions revealed that at lower pH levels (2.0, 3.6 and 5.5 pH), the drug release is mainly governed by the dissolution of Eudragit® E100 from the Eudragit® E100 and Eudragit® RS100 coat. In vitro evaluation of capsules enteric coated with Eudragit® L100 and Eudragit® S100 revealed that a maximum lag time of 3 h and 4 h was obtained, respectively. In vivo roentgenographic evaluation in rabbits revealed that the developed system remained intact until it reaches the targeted region of the gastrointestinal tract, i.e. ileum and colon, where the tablets were released after the dissolution of the enteric coat Eudragit® L100 and Eudragit® S100, respectively.Conclusion: The developed system exhibited a promising targeting behavior and hence may be used for the treatment of inflammatory bowel disease.

Preparation and in vitro characterization of the transdermal drug delivery system containing tamoxifen citrate for breast cancer

A matrix-type transdermal drug delivery system of tamoxifen citrate was developed by using a different ratio of eudragit- RL100, hydroxypropyl methyl cellulose (HPMC-K15), and ethyl cellulose (EC), by the solvent evaporation technique.The effect of the binary mixture of polymers with a penetration enhancer on the physical chemical parameters including, thickness, folding endurance, uniformity of drug content, moisture content, moisture uptake, tensile strength, and in vitro drug permeation were evaluated. The in vitro drug permeation studies were conducted by using modified Keshary-Chein diffusion cells through female Sprague Dawley rat skin using pH 7.4 phosphate buffer saline (PBS).The selected formulation’s stability studies were conducted as per the International Conference on Harmonization (ICH) guidelines, and did not show any degradation of the drug.

Porous microcapsule formation with microsieve emulsification

A simple route is presented to prepare core–shell Eudragit microcapsules through a solvent extraction method with the use of microsieve emulsification. Droplets from a solution of Eudragit FS 30D (a commercial copolymer of poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid) 7:3:1) and hexadecane in dichloromethane are dispersed into water, using a micro-engineered membrane with well-defined pores, in a cross-flow setting. The dichloromethane is extracted from the droplets, which induces demixing in the droplets, leading to a hexadecane-rich core, and an Eudragit-rich shell. The obtained microcapsules have a narrow size distribution due to the microsieve emulsification process. The capsules have a porous shell as shown by SEM and AFM measurements. Their porosity and pore size is dependent on the ratios of Eudragit and hexadecane in the dispersed phase. At pH 7.1 and above Eudragit (FS 30D) dissolves in water; this pH change is used to release the contents of the microcapsule.

Improved drug delivery to the lower intestinal tract with tablets compression-coated with enteric/nonenteric polymer powder blends

The objective of this study was to develop pH-erosion-controlled compression-coated tablets for potential colonic drug delivery with improved gastric resistance and pulsatile release based on compression-coatings of powder blends of the enteric polymer Eudragit® L100-55 and the extended release polymer ethylcellulose. Tablet cores containing model drugs of varying solubilities (acetaminophen, carbamazepine and chlorpheniramine maleate) were compression-coated with different ratios of Eudragit® L100-55:ethylcellulose 10cP FP at different compression forces and tablet core:compression-coat ratios. The compression-coated tablets were characterized by drug release, media uptake, erosion behaviour and wettability. All drugs were released in a pulsatile fashion in higher pH-media after a lag time, which was controlled by the erosion properties of the Eudragit L:ethylcellulose compression-coating. The addition of ethylcellulose avoided premature drug release in lower pH-media and significantly increased the lag time in higher pH-media because of a reduction in wettability, media uptake and erosion of the compression-coatings. Importantly, ethylcellulose also reduced the pH-dependency of the erosion process between pH 5.5 and 7.4. The lag time could also be increased by increasing the compression force and decreasing the core:compression-coat ratio. In conclusion, tablets compression-coated with blends of Eudragit L and ethylcellulose resulted in excellent release properties for potential targeting to the lower intestinal tract with no release in lower pH-media and rapid release after a controllable lag time in higher pH-media.

Development of Sustained Release Capsules Containing “Coated Matrix Granules of Metoprolol Tartrate”

The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet granulation method with subsequent coating. Optimized formulation of metoprolol tartrate was formed by using 30% HPMC K100M, 20% EC, and ratio of Eudragit® RS/RL as 97.5:2.5 at 25% coating level. Capsules were filled with free flowing optimized granules of uniform drug content. This extended the release period upto 12 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC and EC had been coupled satisfactorily with the controlled resistance offered by Eudragit® RS. The release mechanism of capsules followed Korsemeyer-Peppas model that indicated significant contribution of erosion effect of hydrophilic polymer. Biopharmaceutical study of this optimized dosage form in rabbit model showed 10 h prolonged drug release in vivo. A close correlation (R(2) = 0.9434) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with subsequent coating by fluidized bed technique, is a suitable method to formulate sustained release capsules of metoprolol tartrate and it can perform therapeutically better than conventional immediate release dosage form.

Sustained release coating of tablets with Eudragit ® RS/RL using a novel electrostatic dry powder coating process

The objectives of this study were to develop an electrostatic dry powder coating process for sustained coating tablets with Eudragit ® RS/RL and to investigate the effects of various factors and operating conditions on the coating process and drug release profile. A liquid plasticizer (triethyl citrate) was sprayed onto the surface of the tablets followed by spraying coating powder by an electrostatic spray gun. The powder coated tablets were cured at elevated temperature for a film formation. Liquid plasticizer played important roles in lowering down the glass transition temperature ( T g) of the coating polymer and increasing the surface electrical conduction of tablet cores. Electrostatic assisted coating deposition was confirmed by the fact that higher coating level was obtained with electrical charging than the ones without it. The micrographs of scanning electron microscopy (SEM) of coated tablets showed that the film formation mainly occurred during the curing step. Higher curing temperature and longer curing time help enhance the film formation. The in vitro drug release profiles indicated that curing time, temperature, coating level and ratio of Eudragit ® RS/RL were the main factors affecting the sustained release profile. The electrostatic dry powder coating process has been demonstrated to be an alternative for tablet sustained release coating with Eudragit ® RS and RL.

Preparation of pH-dependent modified-release pellets of urapidil to improve its bioavailability

Objective: Modified-release pellets containing urapidil were developed and its in vivo bioavailability was investigated.Methods: Lactose and MCC were used as the main fillers to prepare drug-layer pellets by the powder layering method using centrifugal granulation, and coated in a fluidized bed coater. Pellets with different drug release characteristics were prepared with a methacrylic acid copolymer aqueous dispersion.Results: Using commercial German capsules as the reference (R), two coating formulations were selected for tests after optimization: pH-dependent pellets with a ratio of Eudragit® NE30D/L30D55 of 10:1, a 3% coating level (T1), and pH-independent pellets with a Eudragit® NE30D coating level (T2) of 3.5%. The bioavailability of the pellets (T1, T2, containing 30 mg urapidil) was determined in six healthy subjects after oral administration of a single dose, for a period of three weeks, in the form of a crossover design with a wash-out period of one week. The plasma concentrations of urapidil were determined by HPLC with UV detection. The Cmax (maximum concentration), Tmax, and MRT of T1 were 311.7 ng/mL, 5.3 h and 8.3 h, respectively. T1 was bioequivalent to R, with a relative bioavailability 110.9%. The Cmax and Tmax, of T2 were 105.3 ng/mL and 13.3 h, respectively, and the relative bioavailability was 72.7%.Conclusion: The pH-dependent urapidil pellets have a high bioavailability.

Preparation and characterization of sustained-release microspheres of chlorpromazine

Sustained release microspheres of chlorpromazine were prepared from Eudragit® RS 100 by an emulsion-solvent evaporation method using a six-baffled vessel. The morphology of microspheres was characterized by scanning electron microscopy (SEM). In the presence of aluminium tristearate (5%), microspheres were spherical in shape and uniform. The release of chlorpromazine from microspheres was pH-independent. With increasing amount of aluminium tristearate and increasing ratio of Eudragit® RS 100/drug from 1:1 to 9:1, the particle size of chlorpromazine microspheres was reduced and the release rate decreased. The microspheres prepared with the polymer/drug ratio of 9:l produced a 12–h sustained release pattern.

Evaluation of films used in development of a novel controlled-release system for gastric retention

A novel gastric retention system was developed consisting of a tablet coated with a porous membrane. The membrane consisted of aqueous dispersions of methyl methacrylate copolymers, plasticizers, anti tacking and anti foaming agents. This article presents research work performed in order to characterize these membranes. The films were cast on glass plates coated with teflon. The films were dried at 30°C in a vacuum oven. The three main properties studied on these films were as follows: (1) Transport of drugs across the membrane; (2) mechanical properties; (3) thermo-mechanical properties. These properties were studied to produce a film having the desired characteristics for drug release and mechanical strength. It was observed that the permeability of the drug decreased slightly with increase in the Eudragit® NE 30D concentration. This result correlated well with dissolution rate constants of tablets at 15% coating level. The thermo-mechanical studies helped to understand the results from permeability studies. Based on mechanical properties, a 70:30 ratio of Eudragit® RL 30D and NE 30D was found to be optimum. The study has shown that the evaluation of films will be helpful in providing guidelines in selecting the membrane for the gastric retention system.

Preparation and evaluation of slow-release pan-coated indomethacin granules.

Granules containing indomethacin crystals are coated with Eudragit solutions of different RL/RS ratios using a pan coating technique. The process is reproducible with regard to drug content, inexpensive and the formed granules were directly compressed into tablets. In vitro release of indomethacin from coated granules, tablets and capsules was studied as a function of different ratios of Eudragit RL/RS in the coating solution. The release of the drug was significantly reduced by the coating process in comparison with a formulation made from uncoated granules, prepared using 10 per cent gelatin solution as a binder. Release data were found to follow a diffusion-controlled model.