Comparison of the fragility index of different eudragit polymers determined by activation enthalpies

The present study aimed to apply fragility index (m) of polymers in the determination of the optimal amount of plasticizer in polymer films. The fragility index of different Eudragit polymers (RS, RL, EPO) was assessed by differential scanning calorimerty (DSC), applying the Arrhenius connection (logq–1/T _g). The fragility of Eudragit EPO films proved to be the highest, while in the case of RS and RL, the increase of the alkyl-chain length caused the increase of fragility. Studying the effect of plasticizer (triethyl citrate, TEC) on the m value of Eudragit RL and RS films, a near linear reduction of the fragility index could be observed between 5–30% TEC concentration, but above 30%, this value leveled out to constant.     

Polymethylmethacrylate derivatives Eudragit E100 and L100: Interactions and complexation with surfactants

Precipitation or coprecipitation of polyelectrolytes has been largely investigated. However, the precipitation of polyelectrolytes via addition of charged and non‐charged surfactants has not been systematically studied and reported. Consequently, the aim of this work is to investigate the effect of different surfactants (anionic, cationic, non‐charged and zwitterionic) on the precipitation of cationic and anionic polymethylmethacrylate polymers (Eudragit). The surfactants effect has been investigated as a function of their concentration. Special attention has been dedicated to the CMC range and to the colloidal characterization of the formed dispersions. Moreover, the effect of salt (NaCl) and pH was also addressed. It is pointed out that non‐ionic and zwitterionic surfactants do not interact with charged Eudragit E100 and L100. For oppositely charged Eudragit E100/SDS and Eudragit L100/CTAB, precipitation occurs, and the obtained dispersions have been characterized in terms of particle size distribution and zeta potential. It was established that the binding of SDS molecules to Eudragit E100 polymer chains is made through the negative charges of the surfactant heads under the CMC value whereas binding of CTAB to Eudragit L100 chains is made at a CTAB concentration 5 times above its CMC. For Eudragit E100/SDS system, a more acidic medium induces aggregation. A same result was observed for the Eudragit L100/CTAB at a more basic pH. Moreover, it was observed that increasing salt concentration (higher than 100 mM) led to aggregation as generally observed for polycations/anionic surfactant systems.     

pH‐Sensitive methacrylic acid–methyl methacrylate copolymer Eudragit L100 and dimethylaminoethyl methacrylate,butyl methacrylate,and methyl methacrylate tri‐copolymer Eudragit E100

Poly (methyl methacrylate) derivatives such as Eudragit are largely used for drug encapsulation and in controlled oral drug delivery. With special focusing on those applications, solubilization and precipitation conditions of two pH‐sensitive Eudragit polymers, namely, L100 and E100, were investigated via systematic studies. Effects of various physicochemical parameters such as pH, polymer concentration, salinity, buffer concentration, and incubation time on the solubilization and precipitation of these polymers were investigated. In addition, pH titration of both polymers was reported. Considering both macroscopic and quantitative aspects such as the final mean particle size, size distribution, morphology, and the zeta potential, it was established that the different precited parameters could not be dissociated and exert a synergic action on the solubilization and precipitation of both polymers. Titration curves revealed two equivalences that helped estimating carboxylic content of Eudragit L100 (6 mmol/g) and ammonium content of Eudragit E100 (4 mmol/g). In this study, the solubilization and the precipitation domains were for the first time clearly established by considering the above‐mentioned parameters. Moreover, it was found that Eudragit L100 and E100 cannot be considered as classic polyelectrolytes; in fact, solubilization and precipitation domains were not affected by ionic strength.     

UNDERSTANDING THE MECHANICAL PROPERTIES OF SINGLE MICRO-PARTICLES AND THEIR COMPACTION BEHAVIOUR

The compaction of particulate materials to form tablets is increasingly employed as a final dosage form for functional products due to its simplicity and low cost. However, the functionality of some products may be impaired due to the high compression pressures required. The general aim of the current study is to understand the relationship between the mechanical properties of single feed particles （〈 100μm） and their compaction behaviour in order to produce tablets at low compression pressure with acceptable strength. The materials studied were pharmaceutical excipients, comprising three enteric polymer particles and three different powders in the form of agglomerates. The mechanical properties of the individual particles or agglomerates were determined by a micromanipulation technique. The samples were also compacted in cylindrical tableting dies. It was observed that there was a strong correlation between the forces required to cause the fracture of the single particles and those derived from the compaction measurements as determined using an existing analysis.     

Formulation and Evaluation of 5-FU Loaded Eudragit Microspheres: Effect of Various Eudragit on Micromeretic Properties of Microspheres

The aim of the present study was to prepare and evaluate microspheres of Eudragit (RS, RL and RSPO) containing an anticancer drug 5-FU. Microspheres were prepared by O/O solvent evaporation method using a acetone/liquid paraffin system. Magnesium stearate was used as the droplet stabilizer and n-hexane was added to harden the microspheres. The prepared microspheres were characterized for their micromeretic properties and entrapment efficiency; as well by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), thin layer chromatography (TLC) and scanning electron microscopy (SEM) revealed the crystalline nature of drug in a final state. The in vitro release studies were performed in a Phosphate Buffer Solution (PBS) pH 7.4. The best fit release kinetics was achieved with a Higuchi plot. The yields of preparation and entrapment efficiencies were very high with a larger particle size for all the formulations. Mean particle size, entrapment efficiency and production yield were highly influenced by the type of polymer and polymer concentration. It is concluded from the present investigation that various Eudragit are promising controlled release carriers for 5-FU.     

pH-sensitive polymer-assisted refolding of urea-denatured fibroblast growth factor

A pH-responsive polymer Eudragit S-100 has been found to assist in correct folding of FGF-2(fibroblast growth factor-2) denatured with 8 mol/L urea and 10 mmol/L dithiothreitol at pH 7.2.The refolding of FGF-2 was performed by directly diluting denatured FGF-2 into a refolding buffer containing Eudragit S-100.The ability of Eudragit S-100 to enhance protein refolding level was investigated using MTr method,fluorescence emission spectroscopy and reverse phase HPLC.On the other hand,the result shows the ab...     

Coating Polymer-plasticizer Interaction in Relation to the Enthalpy Relaxation of Polymer

In the course of the formulation of coated dosage forms, the selection of the suitable composition of the coating system is of great importance in respect of the final dosage form. Since the applied coating systems are multicomponent, the possible interactions between the components determine the physico-chemical stability of the formulated dosage form, the drug release process, as well as the formulation parameters. In the present study, the influence of the applied plasticizer, dibutyl sebacate on the enthalpy relaxation of casted Eudragit L 30D films was determined as a function of the plasticizer concentration. The enthalpy relaxation was recorded by DSC during the applied isothermal recovery process of Eudragit films. The obtained results indicate that enthalpy relaxation can be measured by DSC at 20 mass/mass% dibutyl sebacate concentration, which refers to the increased molecular mobility consequently to the effect of the interaction between the polymer and plasticizer. This revised version was published online in August 2006 with corrections to the Cover Date.     

Thermoanalytical behaviour of some coating free films

Differential scanning calorimetry (DSC) was used in the investigation of the behaviour of coating free films. The films were produced from two film-forming polymers which are chemically different but equally used for producing controlled-release dosage forms: Eudragit NE 30 D (synthetically produced polymethacrylate copolymer) and LustreClear product (mixture containing natural and semi-synthetic components: microcrystalline cellulose, hydroxy-ethyl cellulose, carrageenan and polyethylene glycol). During their comparative analysis the characteristic parameters of the DSC curves obtained with dynamic measurement method were used and their changes as a function of storage conditions and storage time were observed. It was found that the thermoanalytical behaviour of the examined methacrylate-based Eudragit NE and cellulose-based LustreClear films was different. The specific enthalpy change of Eudragit NE fresh films was very little, but it increased considerably during storage. The specific enthalpy change of LustreClear films was much greater but its value shows only a slight further increase during storage. The results obtained help to choose the proper temperature for coating and drying.     

Formulation and Optimization of Alogliptin-Loaded Polymeric Nanoparticles: In Vitro to In Vivo Assessment

The nano-drug delivery system has gained greater acceptability for poorly soluble drugs. Alogliptin (ALG) is a FDA-approved oral anti-hyperglycemic drug that inhibits dipeptidyl peptidase-4. The present study is designed to prepare polymeric ALG nanoparticles (NPs) for the management of diabetes. ALG-NPs were prepared using the nanoprecipitation method and further optimized by Box–Behnken experimental design (BBD). The formulation was optimized by varying the independent variables Eudragit RSPO (A), Tween 20 (B), and sonication time (C), and the effects on the hydrodynamic diameter (Y1) and entrapment efficiency (Y2) were evaluated. The optimized ALG-NPs were further evaluated for in vitro release, intestinal permeation, and pharmacokinetic and anti-diabetic activity. The prepared ALG-NPs show a hydrodynamic diameter of between 272.34 nm and 482.87 nm, and an entrapment efficiency of between 64.43 and 95.21%. The in vitro release data of ALG-NPs reveals a prolonged release pattern (84.52 ± 4.1%) in 24 h. The permeation study results show a 2.35-fold higher permeation flux than pure ALG. ALG-NPs exhibit a significantly (p < 0.05) higher pharmacokinetic profile than pure ALG. They also significantly (p < 0.05) reduce the blood sugar levels as compared to pure ALG. The findings of the study support the application of ALG-entrapped Eudragit RSPO nanoparticles as an alternative carrier for the improvement of therapeutic activity.     

Colon specific chitosan microspheres for chronotherapy of chronic stable angina

In the present work, chitosan microspheres with a mean diameter between 6.32 μm and 9.44 μm, were produced by emulsion cross-linking of chitosan, and tested for chronotherapy of chronic stable angina. Aiming at developing a suitable colon specific strategy, diltiazem hydrochloride (DTZ) was encapsulated in the microspheres, following Eudragit S-100 coating by solvent evaporation technique, exploiting the advantages of microbiological properties of chitosan and pH dependent solubility of Eudragit S-100. Different microsphere formulations were prepared varying the ratio DTZ:chitosan (1:2 to 1:10), stirring speed (1000-2000 rpm), and the concentration of emulsifier Span 80 (0.5-1.5% (w/v)). The effect of these variables on the particle size and encapsulation parameters (production yield (PY), loading capacity (LC), encapsulation efficiency (EE)) was evaluated to develop an optimized formulation. In vitro release study of non-coated chitosan microspheres in simulated gastrointestinal (GI) fluid exhibited a burst release pattern in the first hour, whereas Eudragit S-100 coating allowed producing systems of controlled release diffusion fitting to the Higuchi model, and thus suitable for colon-specific drug delivery. DSC analysis indicated that DTZ was dispersed within the microspheres matrix. Scanning electron microscopy revealed that the microspheres were spherical and had a smooth surface. Chitosan biodegradability was proven by the enhanced release rate of DTZ in presence of rat caecal contents.