Eudragit RSPM Research Articles

Some Variables Affecting the Formulation of Pentoxifylline (PTX) as a Solid Sustained Release Dosage Form

An inert matrix that is used to control the release of (PTX) was prepared using Eudragit RL100 and RSPM types as matrix forming agent . The matrices were prepared by either dry granulation(slugging) , or wet granulation method using chloroform as a solvent evaporation vehichle. The cumulative release was adjusted by using polyvinylpyrollidone (PVP) or ethylcellulose (EC) polymers .The results indicated that both methods of preparation were valid for incorporation PTX as a sustained release granules .Moreover ,the results revealed that best polymer used was Eudragit RSPM in 3:20 polymer drug ratio .Besides to that , the results indicated that the release profiles were affected by pH- medium , PVP and EC addition as an enhancer or retardant polymer used respectively. As well as to the method of preparation .
 Key words : Pentoxifylline Sustained Retease , Eudragit RS , RL .

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

PurposeThe aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form.Materials and methodsSustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release.ResultsIn vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031). The pharmacokinetic results indicated that the area under the curve (AUC0–∞) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton®) and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022).ConclusionThe prepared floating tablets of ITO HCl (F10) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

A new wet conductivimetric method to estimate the drug percolation threshold.

The main objectives of this work are to study the behavior of fluid imbibition into a consolidated matrix through a wet invasive conductivimetric technique, to investigate if the changes in the behavior observed can be related to the drug percolation threshold, and to use this technique for its estimation. Matrix tablets were prepared using five sieving fractions of KCl and Eudragit RS-PM. In vitro release assays were carried out on 45 batches. The drug percolation thresholds were estimated following the method of Leuenberger and Bonny, and the results were compared to the obtained employing the conductivimetric technique described in this paper. The wet conductivimetric technique and the standard method provided similar results for the estimation of the percolation threshold. The presented technique also provides quantitative information about the consolidated matrix. A new apparatus has been developed for the study of the conductivimetric behavior of matrix tablets during water uptake. This technique provides measurable parameters of fluid penetration and can be used to estimate the drug percolation threshold, providing similar results to the Leuenberger and Bonny method and being clearly faster.

Didanosine extended-release matrix tablets: optimization of formulation variables using statistical experimental design

Statistical experimental design was applied to evaluate the influence of some process and formulation variables and possible interactions among such variables, on didanosine release from directly-compressed matrix tablets based on blends of two insoluble polymers, Eudragit RS-PM and Ethocel 100, with the final goal of drug release behavior optimization. The considered responses were the percent of drug released at three determined times, the dissolution efficiency at 6 h and the time to dissolve 10% of drug. Four independent variables were considered: tablet compression force, ratio between the polymers and their particle size, and drug content. The preliminary screening step, carried out by means of a 12-run asymmetric screening matrix according to a D-optimal design strategy, allowed evaluation of the effects of different levels of each variable. The drug content and the polymers ratio had the most important effect on drug release, which, moreover, was favored by greater polymers particle size; on the contrary the compression force did not have a significant effect. The Doehlert design was then applied for a response-surface study, in order to study in depth the effects of the most important variables. The desirability function was used to simultaneously optimize the five considered responses, each having a different target. This procedure allowed selection, in the studied experimental domain, of the best formulation conditions to optimize drug release rate. The experimental values obtained from the optimized formulation highly agreed with the predicted values. The results demonstrated the reliability of the model in the preparation of extended-release matrix tablets with predictable drug release profiles.

Development of sustained release matrix tablets of didanosine containing methacrylic and ethylcellulose polymers

Didanosine, a nucleoside analog used in the treatment of acquired immuno deficiency syndrome (AIDS), has been incorporated into directly compressed monolythic matrices whose excipients were mixtures at different ratios of a methacrylic resin (Eudragit RSPM) and an ethylcellulose (Ethocel 100), both water-insoluble and pH-independent polymers. Technological characterization (drug particle morphology, mean weight, diameter, thickness and hardness of tablets) was carried out and in vitro drug release behaviour was measured using the USP basket apparatus. The effect of varying the Eudragit–Ethocel ratio, as well as the drug–polymeric matrix ratio, was evaluated. The results showed the suitability of Eudragit–Ethocel mixtures as matrix-forming material for didanosine sustained release formulations. Combination of the moderate swelling properties of Eudragit RSPM with the plastic properties of the more hydrophobic Ethocel 100 allowed suitable modulation of didanosine release.

Protein Retention in Chitosan-Alginate Microcapsules Modified for Possible Oralprotein Deliverywith Selected Excipients

The protein retention characteristics of chitosan-alginate microcapsules modified with selected excipients were evaluated in vitro for oral protein delivery using Bovine serum albumin (BSA) as the 'model' protein. The microcapsules were prepared by extruding alginate solution containing BSA and either talc, Eudragit L100, Eudragit RSPM, microcrystalline cellulose (MCC) or HPMCAS, into chitosan/calcium chloride solution. Protein retention in microcapsules at different pH of the elution medium was determined spectrophotometrically at e max of 280 nm. Microcapsules containing MCC and talc had the highest protein retention capacity, with 68% and 60%, respectively, of protein still available in the core of the microcapsules after 9 h at pH 1.2, while HPMCAS failed to retain any protein after 9 h at the same pH. Protein retention in microcapsules modified with other additives was intermediate. At higher pH values, microcapsules containing talc still exerted the highest protein retention of 77% (pH 3) and 85% (pH 6), followed by microcapsules containing Eudragit RS PM, 65% (pH 3) and 80% (pH 6), after 9 h. This work has demonstrated that blending the core with suitable excipient enhanced protein retention capacity of chitosanalginate microcapsules. This technology can be employed in oral delivery of protein/vaccines to human and aquaculture.

The role of the drug/excipient particle size ratio in the percolation model for tablets.

In previous papers, a linear relationship between drug particle size and drug percolation threshold was found in inert matrix tablets. The main objectives of the present work are: to study the influence of the excipient particle size on the drug percolation threshold and to investigate if the change in the drug percolation threshold is due either to the absolute or to the relative drug particle size. Matrix tablets have been prepared using KCl (7 different particle size fractions) as a drug model and Eudragit RS-PM (4 granulommetric fractions) as matrix forming material. In vitro release assays were carried out on the 66 lots of tablets. The drug percolation thresholds were estimated following the method of Bonny and Leuenberger. The particle size of the excipient has shown an opposite effect to the drug size on the drug percolation threshold. Nevertheless, the influence of drug and excipient sizes on the drug percolation threshold are of the same magnitude. The drug percolation threshold depends linearly on the relative drug particle size. This finding is in agreement with percolation theory and can facilitate the use of the percolation threshold as a preformulation parameter to improve the pharmaceutical dosage forms design.

FORMULATION AND EVALUATION OF CONTROLLED RELEASE IBUPROFEN TABLETS

Controlled release ibuprofen tablets were prepared by coevaporation technique using Eudragit RSPM, ethylcellulose 20, Aerosil R972 and Aerosil 200 as carriers and Avicel pH102 as filler. The effect of different compression forces on the release rate of the drug was studied. The carriers used produce retardation in the release rate of ibuprofen in the following manner: Eudragit RSPM > ethylcellulose 20 > Aerosil R972 > Aerosil 200. The dependence of release rate (K) on hardness (H) may be approximated by the equation, Ln K = a H + b. The release mechanism follows zero order kinetic. The antiinflammatory activity of the coevaporates was studied in albino rats using trypan-blue method. The coevaporates were also tested in albino mice for their analgesic activity using hot plate and p-benzoquinone induced writhing methods. The obtained results revealed that Eudragit RSPM and Aerosil 200 were the most effective in sustaining the antiinflammatory and analgesic actions of ibuprofen, while ethylcellulose 20 was the least effective. Histological examination of rat's stomach proved the efficiency of the tested coevaporates in inhibiting the ulcerogenic effects caused by the plain drug.

Relationship between drug percolation threshold and particle size in matrix tablets.

Since a previous qualitative study carried out by us showed the existence of an important influence of the particle size on the percolation thresholds and taking into account that the existing theoretical models can only provide qualitative explanation to this influence, the purpose of this work is to carry out the first quantitative study of the influence of the particle size over the drug percolation thresholds. Matrix tablets have been elaborated using potassium chloride as drug model and Eudragit RS-PM as matrix forming material. Five different KCl particle size fractions have been employed whereas the Eudragit RS-PM particle size was kept constant. In-vitro release assays were carried out for all the elaborated lots. The drug percolation thresholds were estimated following the method proposed by Bonny and Leuenberger. A linear relationship has been found between the drug particle size and the corresponding drug percolation threshold. This finding confirms the results previously obtained in our qualitative study and has important repercussions in the design of pharmaceutical solid dosage forms. If this linear behaviour is general, the percolation threshold can soon become a useful preformulation parameter.

Matrix Type Tablet Formulation for Controlled Release of Highly Water Soluble Drugs

Matrix type formulations with dicalcium phosphate dihydrate (DCPD) using a polymeric binder (Eudragit RSPM®) to obtain controlled release of highly water soluble drugs has been investigated.The drug, DCPD and Eudragit RSPM® were granulated using isopropyl alcohol with and without a plasticizer (Diethyl phthalate, DEP). Addition of Eudragit did not appear to affect the release profile. However, addition of a plasticizer had a significant effect on the rate of release. The release appears to follow first order kinetics and the rate constant decreased linearly with increasing DEP concentration.A directly compressible mixture was also formulated by coating DCPD particles with DEP with and without Eudragit RSPM®.

Effects of Compression Force and Type of Fillers on Release of Diclofenac Sodium from Matrix Tablets

AbstractThe influence of compression force and type of fillers on the release pattern of diclofenac sodium from wet-granulated tablet matrices containing Emcompress and lactose as fillers with Eudragit RSPM as a matrix additive was determined. The release pattern of diclofenac sodium from these matrices in USP phosphate buffer pH 7.2 at 37 ° C were found to be independent of compression forces whereas the ratios of insoluble (Emcompress) to soluble filler (lactose) appeared to greatly influence the drug release rate as evidenced in the increased release rate with decreasing Emcompress content. The kinetics of drug release was determined and found to precisely comform to the Higuchi's planar matrix model. A theoretical approach to predict the drug release rate from a designed system was presented and found to be satisfactorily predictive.

Relationship of Film Properties to Drug Release from Monolithic Films Containing Adjuvants

The rate of drug release from a polymeric matrix system was influenced by the physical and chemical properties of the monolithic films. The model drugs, salicylic acid and chlorpheniramine maleate, and two poly(methyl methacrylate) copolymers of different permeabilities (Eudragit RL and Eudragit RS), with and without additional adjuvants, were used to form monolithic matrix films for controlled drug release. Adjuvants, including polyethylene glycols (PEG 400 and PEG 8000) and poly(vinylpyrrolidones) (PVP‐K15 and PVP‐K90), were incorporated into films of Eudragit RL PM and Eudragit RS PM. The moisture permeation constant, glass transition temperature (Tg), tensile strength, and drug release profiles were determined for each acrylic resin slab to correlate the physicochemical and physicomechanical film properties to observed drug release. Faster rates of drug diffusion were observed with the addition of PEG 400 to the films, because of its plasticizing effect and the resultant increased moisture permeability of the matrix. An exception existed with the Eudragit RL PM film containing salicylic acid where drug‐polymer interactions inhibited drug diffusion. The small changes in moisture permeability, Tg, and tensile strength observed with incorporation of the PVPs had an insignificant influence on the dissolution results for salicylic acid from Eudragit RS PM films. Increases in the tensile strength and Tg after addition of PVP to the Eudragit RS PM matrix support the observed decreased rate of diffusion for chlorpheniramine maleate. The pores formed by migration of the hydrophilic adjuvants from the films altered the diffusion kinetics of the matrix, compared with that of the nonporous polymer, when only the antihistamine was present.

Sustained Release Tablet Formulation for a New Iron Chelator

AbstractSustained release tablet formulations for a new orally active iron chelator (1, 2, dimethyl-3-hydroxy-pyrid-4-one, DMHP or L1) have been developed. Coprecipitates containing DMHP and polymer were prepared and compressed into matrix-type tablets. The dissolution profiles as a function of (1) the type of polymer, and (2) polymer content, were determined. Both Eudragit types (RLPM and RSPM) and all hydroxypropylmethylcellulose (HPMC) grades (E4M, E10M, and K4M) exhibited significant sustained release activity. Above a certain ratio, increase in the polymer concentration did not provide any further decrease in the release rates. All grades of HPMC and both Eudragit RSPM and RLPM showed non-Fickian release kinetics. The role of HPMC and Eudragits in the formulation of a sustained release tablet of a water soluble drug is demonstrated.

Physical Characterization and Dissolution Properties of lbuprofen:Eudragit Coprecipitates

lbuprofen:Eudragit coprecipitates were prepared in 10:3 ratios and their physical properties and related dissolution characteristics were determined. The Eudragit polymers used for the studies were three anionics (Eudragit L100, Eudragit L100-55, and Eudragit S-100), one anionic.cationic mixture used in a 1:1 ratio (Eudragit S100 + E100), and four zwitterionics (Eudragits RL 100, RS 100, RSPM, and RLPM). Physical characterizations were made using qualitative and quantitative X-ray diffractometry, IR spectrophotometry, and differential scanning calorimetry (DSC). Except for Eudragit S100 + E100 coprecipitates, no sizeable interaction at a molecular level was detected between the drug and the polymer. The crystalline structure of the drug was slightly modified in the coprecipitates. Regardless of the lack of interaction, dissolution of ibuprofen was retarded from all the coprecipitates studied (except Eudragit L100), especially in the pH 6.8 to 7.5 media in which the drug is freely soluble. The dissolution rate constants of the coprecipitates, calculated using Higuchi equation, demonstrated that dissolution decreased in the order of anionics > zwitterionic > anionic + cationic mixtures. The data obtained suggest that the release mechanisms involved are the swelling and slower dissolution of the polymer matrix relative to precipitated ibuprofen. The coprecipitates possess improved flow properties compared with ibuprofen with the exception of Eudragit RLPM and Eudragit RSPM. Eudragit coprecipitates can be useful tools in preparing ibuprofen sustained-release tablets. The coprecipitation technique used is simple and minimizes the use of organic solvents.

Preparation and characterization of a new controlled release ibuprofen suspension for improving suspendability

A new controlled release suspension of ibuprofen was developed by using ibuprofen microspheres with an acrylic polymer (Eudragit RS-PM TM ). Uniform dispersibility of the microspheres for a period of more than 6 months could be obtained in a low viscous acidic solution of sodium carboxymethylcellulose (CMC) by the addition of d-sorbitol. The presence of d-sorbitol in the acidic medium increased the adsorbed amount of CMC on the microspheres and contributed to build the loose three-dimensional networks of CMC. The coarse microspheres covered with CMC were considered to be held in the networks. This structure of CMC made it possible to maintain the long-term uniform dispersibility. An in vitro drug release test showed no influence of the adsorbed CMC on the release rate. Leakage of drug from the microspheres in the suspension was not found to occur on storage for 6 months.

Sustained Release Matrix of Mebeverine Hydrochloride Using Polyacrylate Resin “Eudragit Retard” Kinetic of Drug Release and Evaluation of a Kinetic Model

AbstractIn this study Eudragit RS PM and RL PM were evaluated as carriers for the preparation of prolonged release solid dispersions of mebeverine hydrochloride by solvent and melting methods. The prepared tablets were examined for dissolution at pH 1.2 and 7.4, Eudragit RS PM and RL PM were found satisfactory as potential slow release carriers. The solid dispersion prepared by the solvent method showed a slow release pattern. Drug release appeared to fit both, first order and Higuchi matrix model kinetics. However, on application of the differential rate treatments, the evidence supported the Higuchi matrix model. Effect of temperatures on dissolution rate was studied for thermodynamic consideration.The drug release was pH-independent until pH 7.4.As the pH increased, the release was significantly reduced due to solubility problem.

Effect of Eudragit Resins and Dibasic Calcium Phosphate on the Compation and Dissolution Behavior of Directly Compressible Controlled-Relase Theophylline Tablet

AbstractThe compaction behavior and release property of tablets made by the combined formulations of Eudragit RLPM and RSPM with or without diabasic calcium phosphate anhydrous (DCPA) using direct compaction were examined. The larger the amount of Eudragit RSPM or DCPA the higher the value of the tensile strenght. A linear realationship was found in the lorgrithm of tensile strength plotted against the porosity of the compacts. The Heckel plot was also used ot evalute the compaction behaviour of tablets. The results indicate that Eudargit RSPM and DCPA are responsible for the good compressiblity of compacts. The contact angle of tablets without DCPA became samller with an increase in the Eudragit RSPM, but exhibited a higher contact angle than tablests with DCPA. The controlled release behavior of theophylline from tablets without DCPA was found and showed a pH-independent property, whereas tablets with DCPA were pH-dependent and exhibited a faster dissolution than tablests without DCPA. The result sugges...

Compaction Properties of Acrylic Resin Polymers with Plastic and Brittle Drugs

Tensile strengths of compacts consisting of acrylic resin polymers in combination with a plastic drug (theophylline) and a brittle drug (sodium sulfathiazole) were investigated. The polymers studied included Eudragit RS PM, RL PM, S 100, L 100, and L 100-55. All compacts were compressed to a solid fraction of 0.81. The solid fraction, rather than compression force, was kept constant in order to account for the differences in packing characteristics and elastic and plastic deformational properties of different materials (1). Tensile strength profiles for the blends of the Eudragit S 100 and RL PM polymers with sodium sulfathiazole included approximately linear relationships between pure drug and pure polymer. The Eudragit L 100-55 exhibited a large peak in the tensile strength of compacts containing 20% sodium sulfathiazole. Significant differences between the physical-mechanical properties of the methacrylate ester and methacrylic acid copolymers were observed where the latter proved to be much stronger at all concentrations. The differences between the two categories of polymers were greater in compacts containing the plastic drug, theophylline. Peaks in tensile strengths were seen for both drugs with all three of the methacrylic acid copolymers, while the methacrylate ester copolymers maintained approximately linear relationships for all ratios of drug and polymer.

Controlled-Release Theophylline Tablet Formulations Containing Acrylic Resins, II. Combination Resin Formulations

AbstractTheophylline tablet formulations containing a combination of cationic and anionic acrylic resins were prepared and evaluated. Equal amounts of Eudragit RSPM (cationic resin) and Eudragit L100 (anionic resin) were included at the 15% level (total polymer content) into the tablet formulations. Pressure-hardness profiles with theophylline-resin compacts (4:1) demonstrated that compacts containing the RSPM resin were the most compressible. The dissolution profiles for theophylline in acidic media showed slower release rates from tablets containing the combined resins than from those containing each of the single resins. It was proposed that this decrease in drug release rate was a result of a solid state interaction between the oppositely charged polymers. As the amount of retardant in the matrix increased, the release rates in acidic media decreased. In pH 7.4 phosphate buffer, much faster release was seen due to the higher solubility of the Eudragit L-100 resin at this pH level. Tablet hardness betw...

A New Approach for Controlling the Release Rate of Pheniramine Aminosalicylate Via Solid Dispersion in Different Types of Eudragit

AbstractCo-precipitates of pheniramine aminosalicylate in different types of Eudragit were prepared. IR spectra indicated the absence of molecular interaction between the drug and Eudragit. The effect of polymer type on the retardation of drug release rate was in the following order: Eudragit S 100> Eudragit L 100> Eudragit RSPM or Eudragit RS 100> Eudragit RLPM or Eudragit RL 100. The concentration of the polymer in the system was a determining factor in controlling the release rate of the drug. As the concentration of the polymer in the system increased, the release rate of the drug decreased.Co-precipitates of the drug in different ratios of Eudragit blends were also prepared. The release rate of the drug decreased by decreasing the concentration of the permeable Eudragit RLPM or Eudragit RSPM in the system.The rapid release rate of the drug from the physical mixtures excluded their application in controlling drug release.