Eudragits are synthetic copolymers of acrylate that have been known as suitable carriers for preparation of sustained release matrices. Solid dispersion (SD) systems which at first had been used to enhance the dissolution rate of poorly water soluble drugs is now widely used in preparation of sustained release matrices. This study was performed in order to evaluate the Eudragit RL and RS solid dispersion systems in preparation of sustained release diclofenac sodium matrices. The effect of drug and polymer mixture preparation and drug polymer ratio on the properties of matrices such as its crushing strength, drug release rate and mechanism were studied. The results showed that increasing the polymer content increased the cl1lshing strength of matrices prepared either from physical mixture or SD system and decreased the rate of drug released. Matrices prepared from SD system were harder than those prepared from physical mixtures and the rate of drug release from former matrices was considerably slower than the latter matrices. Comparison of drug release at the same drug: polymer ratio showed that drug release rate from E.RL matrices was slower than E.RS matrices except in matrices prepared from physical mixture with I: 1 drug: polymer ratio. This was attributed to the electrostatic interaction between polymers and drug. The electrostatic interaction between drug and polymers was confirmed by measuring the amount of drug absorbed on the polymers in the presence of Tween 80 or SLS. As E.RL contains more ammonium groups than E.RS therefore the extent of interaction between dic10fenac sodium and E.RL could be greater than E.RS. This could explain the slower drug release rate from E.RL matrices compared to E.RS. In SD systems the extent of interaction between drug and polymers increased and this retarded the rate of drug released. It was shown that in the most cases diffusion was the main mechanism controlling drug release rate. In conclusion the use of solid dispersion systems is valuble in production of sustained release matrices of E.RL and E.RS and can lead to less polymer consumption compared to physical mixtures of drug and polymer in order to control drug release rate. These systems due to very slow rate of drug release are also useful in production of transdermal drug delivery systems.

A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit vancomycin (VCM) nanoparticles prepared by double emulsion. The purpose of this work was to optimize VCM nanoparticles to improve the physicochemical properties. Nanoparticles were formed by using W1/O/W2 double-emulsion solvent evaporation method using Eudragit RS as a retardant material. Full factorial design was employed to study the effect of independent variables, RPM (X1), amount of emulsifier (X2), stirring rate (X3), volume of organic phase (X4) and volume of aqueous phase (X5), on the dependent variables as production yield, encapsulation efficiency and particle size. The optimum condition for VCM nanoparticles preparation was 1: 2 drug to polymer ratio, 0.2 (%w/w) amount of emulsifier, 25 mL (volume of organic phase), 25 mL (volume of aqueous phase), 3 min (time of stirring) and 26000 RPM. RPM and emulsifier concentrations were the effective factors on the drug loading (R2=90.82). The highest entrapment efficiency was obtained when the ratio of drug to polymer was 1: 3. Zeta (z) potential of the nanoparticles was fairly positive in molecular level. In vitro release study showed two phases: an initial burst for 0.5 h followed by a very slow release pattern during a period of 24 h. The release of VCM was influenced by the drug to polymer ratio and particle size and was found to be diffusion controlled. The best-fit release kinetic was achieved with Peppas model. In conclusion, the VCM nanoparticle preparations showed optimize formulation, which can be useful for oral administrations.

Purpose: The main objective of the present study was to develop the colonic delivery system for 5-aminosalicylic acid (5-ASA) as an anti-inflammatory drug. Methods: Matrix pellets containing various proportions of alginate, calcium and Eudragit® RS were prepared by extrusion-spheronization technique. Thermal treatment was used to investigate the effect of the curing process on the surface morphology, mechanical and physicochemical properties and in vitro drug release profile of pellets. Based on the obtained results optimal formulations were selected to coating by the Eudragit® RS and subjected to a subsequent continuous dissolution test. Results: Image analysis and also scanning electron microscopy results proved acceptable morphology of the pellets. The fourier transform infrared spectroscopy and differential scanning calorimetry studies ruled out any interactions between the formulation’ s components. Curing process did not alter the mechanical properties of pellets. The release rate of the drug from matrices was prolonged due to the decreased porosity of cured pellets. Furthermore, selected cured pellets which coated with Eudragit® RS, prevented undesired premature drug release. Conclusion: Formulation containing 17. 5% calcium, 17. 5% alginate, and a coating level of 10% demonstrated enhanced drug release so that provided resistance to acidic conditions, allowing complete drug release in alkaline pH, mimicking colonic environment. The slow and consistent drug release from this formulation could be used for treatment of a broader range of Inflammatory bowel disease (IBD) patients especially in whom colonic pH levels have been measured at lower than pH 7. 0.

Background and purpose: Inflammatory bowel diseases (IBD) are chronic and recurrent inflammatory disorders of the gastrointestinal tract, classified into two main categories: ulcerative colitis and Crohn's disease. Mesalazine is the most commonly prescribed drug for the treatment of inflammatory bowel disease (IBD); however, its rapid absorption in the small intestine reduces its local effects in the colon. The use of mesalazine in coated pellet form as a multi-unit drug delivery system may enhance its effectiveness compared to conventional pharmaceutical forms such as tablets. Arthritis is one of the extra-intestinal manifestations of IBD, which can be alleviated by acetaminophen. The aim of this study is to design a multi-unit oral drug delivery system (pellets) that simultaneously delivers mesalazine to the large intestine and acetaminophen to the stomach. Materials and methods: In this experimental study, mesalazine pellets were prepared using the extrusion-spheronization method and coated with pH-dependent polymers (Eudragit® L100 and Eudragit® S100) as well as a combination of time-dependent (Eudragit® RS) and pH-dependent polymers (Eudragit® L100). Drug release was evaluated in simulated gastrointestinal environments, and the optimal formulations were identified. Subsequently, acetaminophen was loaded onto the optimized pellets using a fluid bed coater. The drug release profile was assessed using a continuous dissolution testing method. Thermal analysis, infrared spectroscopy, mechanical testing and scanning electron microscopy were performed to evaluate the physicochemical properties and investigate potential interactions. Results: Pellets coated with 40% Eudragit® RS and 60% Eudragit® L100, as well as those coated with 100% Eudragit® S100, were found to be more suitable for colon drug delivery than other formulations. Continuous dissolution testing showed that acetaminophen was released in a pH 1.2 environment within 2 hours, while mesalazine remained intact and reached the large intestine. Physicochemical tests indicated that the pellets had a smooth surface, uniform coating, and appropriate hardness, with no detectable interactions between the drugs and excipients. Conclusion: This study demonstrated that the optimized formulation effectively enables the targeted delivery of acetaminophen to the stomach and mesalazine to the colon in a single dosage form.

Objectives: Microencapsulation is a well-known method that is used to modify and retard drug release. In this study, the preparation of diclofenac sodium and Eudragit RS and/ or RL microcapsules was accomplished in order to asses the suitability of them for production of oral sustained release multiparticulate dosage form of diclofenac sodium. Methods: Microcapsules were prepared using the emulsion solvent evaporation method. The effect of formulation variables namely polymer: drug ratio, type of polymer and inclusion of PEG 400 as a channeling agent were investigated on shape and surface characteristics of microcapsules (by scanning electron microscopy), percentage yield and drug entrapment efficiency, mean particle size (sieve analysis) and drug release profiles (dissolution test). Results: Microscopic examination of microcapsules revealed that all microcapsules were well-shaped and nearly spherical. Percentage yield was more than 90% and drug entrapment efficiency was more than 95% for most of the cases and therefore confirmed the suitability of the method for production of microcapsules with high drug loading. The mean particle size for different microcapsules was in the range of 390 - 589 μm. Drug release was very slow from microcapsules with 3:1 polymer: drug ratio. Increase in stirring speed did not influence the size and release characteristics of microcapsules at 3:1 polymer: drug ratio. Decrease in polymer:drug ratio to 2:1 did not significantly influence the release rate of drug. Further decrease in polymer: drug ratio to 1:1 increased the rate of drug release. However drug release from all formulations was incomplete at the end of dissolution test. Despite the higher water permeability of Eudragit RL both Eudragit types behaved similarly in controlling drug release rate. This observation and also incomplete drug release from all microcapsules were attributed to the probable electrostatic interaction between cationic quaternary ammonium groups in Eudragit RS and RL and diclofenac sodium. The inclusion of 10 or 20% PEG 400 in microcapsule wall resulted in microcapsules with very smooth surface and increased the rate of drug release. Calculation of difference factor revealed that the release profile of microcapsules with 1:1 polymer: drug ratio and containing 10% PEG was similar to commercial sustained release pellets of diclofenac sodium (Modafen). Conclusions: The emulsion solvent evaporation method was successful in production of diclofenac sodium and Eudragit RS or RL microcapsules. The yields of preparation and drug entrapment efficiencies were high for all microcapsules obtained. The drug: polymer ratio and inclusion of PEG 400 influenced the in vitro drug release; however the microencapsulation yield and drug entrapment efficiency were not influenced. The 1:1 polymer: drug ratio produced better release profile for oral drug delivery.

Background: In the previous study it was shown that films prepared from inulin (In) in combination with Eudragit RS (ERS) and RL (ERL) were susceptible to inulinase. Purpose: The aim of this work was to assess the suitability of these combinations for colonic delivery of indomethacin.Methods: Indomethacin was loaded onto non-pareil seeds using fluidized bed apparatus to produce pellets with 20% w/w drug load. Drug loaded pellets were coated with In-ERS in the ratios of 20:80 and 30:70, or In-ERL in the ratio of 20:80 to different coating loads. The release of drug was examined in simulated gastric (for 2 hrs) and small intestine and in the presence of inulinase in simulated colonic medium (for 12 or 24 hrs). Results: The results of this study revealed that incorporation of inulin as a bacterially degradable polysaccharide into ERS or ERL could modulate drug release. Coating level up to 15% significantly affected drug release from In-ERL or In-ERS coated pellets. However further increase in coating load to 20% had no significant effect on drug release from In-ERL coated pellets (f1=9.39). Drug release from In-ERL coated pellets was faster and showed some pH dependency. Conclusions: Formulation coated with In-ERS (20:80) and coating level of 20% was considered more appropriate for colon delivery of indomethacin, as drug release was pH independent and formulation was resistant to drug release in the upper GI media for up to 7 hrs. This formulation was also susceptible to inulinase and released about 40% of indomethacin in the simulated colonic media.

Background and the purpose of the study: The potential of pectin as a bacterially degradable polysaccharide for colon drug delivery has been demonstrated. Due to the high solubility and swelling properties of pectin in aqueous media, it is frequently used in combination with water insoluble polymers for targeting drugs to the colon. The aim of this study was to evaluate free films containing pectin as a bacterially-degradable polysaccharide in combination with Eudragit RL (ERL) and/or RS (ERS) as a coating formulation for colonic drug delivery.Methods: Isolated free films comprising 20% pectin and 80% ERL or ERS and their combination in 1:1 ratio were prepared by casting method. Then, free films were evaluated by water vapor transmission (WVT), swelling and permeability experiments for theophylline and indomethacin in different media.Results: Formulations containing ERL exhibited higher WVT, swelling and permeability compared with formulations containing ERS. The permeability of theophylline through free films composed of pectin and eudragit polymers in simulated colonic media was not significantly different from those obtained in other media. However indomethacin free films containing pectin and ERL showed higher permeation in simulated colonic fluid (SCF) compared to the other media.Major conclusion: Formulation containing pectin and ERL may be suitable as a coating formulation for colon targeted delivery of drugs of low solubility such as indomethacin.