Eudragit RL100 based microspheres for ocular administration of azelastine hydrochloride

In the present study, potential of polymeric microspheres for treatment of allergic conjunctivitis was investigated. Azelastine hydrochloride loaded Eudragit RL100 microspheres were prepared by solvent evaporation technique. The change in drug–polymer ratio on the particle size, zeta potential, entrapment efficiency and in vitro drug release was investigated. As Eudragit concentration ranged from 40 to 80?mg/ml the size range obtained was 4.18–7.36?µm with positive zeta potential. With the increase in drug polymer ratio, the entrapment efficiency was increased with maximum 14.56%. In vitro release studies demonstrated prolonged release of the drug over the period of 6?hr. Scanning electron micrographs showed that microspheres were spherical with distinct solid dense structure. Fourier transform infrared and differential scanning calorimetry studies concluded slight change in peak intensities of drug in microspheres. In vivo studies in rat model indicated that reduction in eosinophil count number was more pronounced in azelastine hydrochloride microspheres than marketed formulation, Azelast®.     

制备因素对丙烯酸树脂缓释微球中硝苯地平释放度的影响

用乳剂－溶剂挥发法制备硝苯地平的丙烯酸树脂缓释微球，微球中药物的释放速率随丙烯酸树脂Eudragit RL/RS比率的增加以及制备时搅拌速率的增加而增大，随内相聚合物浓度的增加及微球粒径的增加而减少，释药50％所需时间与微球粒径呈良好线性，微球的释药速率也随药物含量的增加（从4．2％到16．7％）而增大，并快于药物结晶的溶解速率，但药物含量达26．6％时，微球释药速率明显下并低于药物结晶的[溶解速率，用差热分析和X射线衍射分析证明，药物含量为4．2，9．4和16．7％的微球中药物完全是以非晶态分散的，而含药26．6％，的微球中有药物结晶存在，不同微球释药低于70％时，释放方式均符合Higuchi时间平方根方程。     

Influence of Preparation Factors on the Sustained Release of Nifedipine from Eudragit RL/RS Microspheres

用乳剂—溶剂挥发法制备硝苯地平的丙烯酸树脂缓释微球。微球中药物的释放速度随丙烯酸树脂ＥｕｄｒａｇｉｔＲＬ／ＲＳ比率的增加以及制备时搅拌速率的增加而增大，随内相聚合物浓度的增加及微球粒径的增加而减小，释药５０％所需时间与微球粒径呈良好线性。微球的释药速率也随药物含量的增加（从４．２％到１６．７％）而增大，并快于药物结晶的溶解速率，但药物含量达２６．６％时，微球释药速率明显下降并低于药物结晶的溶解速率。用差热分析和Ｘ射线衍射分析证明，药物含量为４．２，９．４和１６．７％的微球中药物完全是以非晶态分散的，而含药２６．６％的微球中有药物结晶存在。不同微球释药低于７０％时，释放方式均符合Ｈｉｇｕｃｈｉ时间平方根方程。     

Physicochemical properties of enteric films prepared from aqueous dispersions and organic solutions

Cast films composed of mixtures of Eudragit S100:L100 (1:1) and plasticized with triethyl citrate (TEC) were prepared from aqueous dispersions and organic solutions, and the physicochemical properties and the weight loss of cast films during dissolution testing were examined. The tensile strength of the organic cast films was significantly higher and the percent elongation was lower than that of the aqueous cast films. The weight loss of the organic films was also lower than that of the aqueous films. Furthermore, leaching of the TEC from the aqueous films was rapid and the TEC was found to diffuse from the films within one hour at pH 6.0, the pH at which the Eudragit S100:L100 (1:1) films were insoluble. In contrast to the aqueous films, minimal levels of the TEC diffused from the organic cast films, and the disintegration of acrylic polymers occurred simultaneously with the release of TEC from the film during dissolution testing at pH 7.0. For Eudragit L100-55, which could form films at lower TEC levels than Eudragit S100:L100, both the organic and aqueous films showed the same weight loss after four hours in pH 5.0 media. These results demonstrated that for Eudragit S100:L100 cast films, the high levels of TEC needed for film formation from aqueous dispersions resulted in rapid dissolution and disintegration at pH 6.0 and above. While aqueous dispersions are preferred for the coating of solid substrates, for Eudragit S100:L100 film coatings, a change from organic solutions to aqueous dispersions in the coating process will impact film properties and product performance.     

The Preparation and Evaluation of Sustained Release Suppositories Containing Ketoprofen and Eudragit RL 100 by Using Factorial Design

The preparation of ketoprofen (KP) sustained release (SR) suppositories was designed according to the 3² × 2¹ factorial design as three different KP:Eudragit RL 100 ratios (1:0.5, 1:1, 1:2), three particle sizes of prepared granules (250–500, 500–710, and 710–1000 μm) and two different PEG 400:PEG 6000 ratios (40:60, 50:50). The conventional KP suppositories were also prepared by using Witepsol H 15, Massa Estarinum B, Cremao and the mixture of PEG 400:PEG 6000. The dissolution studies of suppositories prepared were carried out according to the USP XXIII basket method in the phosphate buffer (pH = 7.2) at 50 rpm, and it was shown that the dissolution time was sustained up to 8 hours. According to the results of the factorial design, the most important independent variable on t₅₀ and t₈₀ was drug:polymer ratios. The log of partition coefficient of KP was determined as 1.46, showing the high affinity to the oily phase. n exponent and kinetic studies were conducted to explain diffusion mechanism, and it is understood that if the inert KP:Eudragit RL 100 ratio is increased in the particles, the Fickian difusion dominates and the best kinetic turns to Higuchi from the Hixson-Crowell. There is neither crystalline form of KP nor degradation product in the suppositories detected with the differential scanning calorimetry (DSC) studies. In addition to these studies, antiinflammatory activity of SR suppositories also determined that it was significantly extended according to the conventional suppositories.     

聚合物水分散体包衣技术及其应用

目的：水性包衣工艺是江膜包衣的重要发展方向。目前发展较迅速的是聚合物水分散体包衣技术。本文概述其包衣材料、成膜原理和应用特点。方法：结合文献和作者实践,归纳并综述。结果与结论：水分散体包衣技术避免了传统工艺中的环境污染、毒性、不安全和成本高等问题,具有广阔应用前景。     

The effect of pectin on swelling and permeability characteristics of free films containing Eudragit RL and/or RS as a coating formulation aimed for colonic drug delivery

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.     

Lactic acid-induced modifications in films of Eudragit RL and RS aqueous dispersions

Eudragit RL (ERL) and RS (ERS) are polymethacrylate co-polymers, used in film coating of sustained release dosage forms, possessing some hydrophilic properties due to the presence of quaternary ammonium groups (QAG), where ERL contains more of such groups, hence more permeable, than ERS. However, because these groups ionize in solution, they undergo electrostatic interaction with negatively charged species. This phenomenon was utilized in this study to introduce modification in the film properties of ERL and ERS by interaction with lactic acid (LA). Thermal and mechanical analyses were carried out on polymeric free films. DSC showed a shift in Tg of the film while 1H NMR spectroscopy revealed a significant deshielding in the peak of QAGs protons after interaction with LA. Stress-strain test showed an increase in three mechanical parameters of the new film (containing LA): tensile strength to modulus ratio, relative surface energy and toughness index, indicating an enhancement in the mechanical stress resistance. Tablets coated with LA-containing films showed an increase in the release rate and extent and good stability upon aging, compared to those coated with the original film.     

Eudragit NE30D膜的制备及其性能参数的标准化研究

目的考察Eudragit NE30D膜的制备条件,探索膜性能参数的标准化方法。方法分别使用质量分数5%、7.5%、10%、12.5%、15%的Eudragit NE30D水分散液,考察了1、2 m L两种体积和25、40、55℃温度对Eudragit NE30D膜制备的影响,比较了其厚度、均匀度、表面平滑度、含水量、透湿量、抗张强度、断裂伸长率。结果 Eudragit NE30D适宜的成膜温度为40℃,成膜时间4~6 h,操作体积为1 m L,质量分数为5%~10%,控制含水量5%。制得的膜标准化参数、透湿性和机械性能的重现性良好。结论本法简单可行,为研究Eudragit NE30D性能提供参考。     

A Simple and Rapid Method for the Quantification of Eudragit RS100 and RL100 Poly(methacrylates) in Sustained-Release Dosage Forms

A colorimetric ion-pair complexation method has been developed which provides a simple and rapid way of quantifying Eudragit RS100 and RL100 in pharmaceutical dosage forms. The quaternary ammonium groupings in these polymers appear to form an ion-pair complex with the dye tropaeolin OOO. When extracted into an organic phase, the optical density at 484 nm is linearly related to polymer concentration. Control of pH is important, and it should be maintained within the range 4.5 to 9.0. A wide range of pharmaceutical excipients commonly used in tablet, pellet, and film-coating formulations did not interfere with formation of the complex, but certain drugs were found to significantly enhance or decrease the assay response. Good reproducibility, precision, and accuracy were demonstrated when the method was applied to a film-coated pellet formulation containing an interfering drug (promethazine hydrochloride). However, removal of interfering substances must be optimized. The method was sufficiently sensitive for the determination of polymer on a single dose unit of encapsulated beads.     

Effects of plasticizers and surfactants on the film forming properties of hydroxypropyl methylcellulose for the coating of diclofenac sodium tablets

Hydroxy propyl methyl cellulose (HPMC) 5cPs, an aqueous soluble polymer was employed for coating diclofenac sodium (DFS) tablets 25 mg for protecting the integrity of the drug yet rendering the drug to release at a faster rate on contact with the gastric environment. Proper optimization for the aqueous based film coating formulation was undertaken primarily employing plasticizers like polyethylene glycol (PEG) 400 and propylene glycol (PG). The defect free selected formulations were further subjected for studying the effects of surfactants like sodium lauryl sulphate (SLS) and Tween-80 along with the plasticizers. The quality of the aqueous film coats or the plasticizer efficiency in case of PEG-400 is in the order 1.5 > 0.5 > 1.0% and for PG 1 > 4 > 3% which can be stated on the basis of less incidence of major coat defects like chipping, cracking, orange peel, roughness, blistering, blooming, picking. The quality of aqueous film coat or the surfactant efficiency in case of SLS + PEG-400 is in the order 0.3 < 0.5 < 0.1% and SLS + PG is in the order 0.5 < 0.1 < 0.3%. In case of Tween-80 + PEG-400 the order is 0.3 < 0.5 < 0.1% and Tween-80 + PG is in the order 0.3 < 0.1 < 0.5%. Elegant film formation can be stated from fewer incidences of coat defects. The obtained coated tablets eventually satisfied all the normal physical parameters like thickness, weights, and weight gain, drug content, crushing strength, percent friability, disintegration time, dissolution profile and possible drug–polymer interactions. ANOVA was undertaken followed by Dunnet multiple comparison for the dissolution profile considering uncoated as the standard. The difference was considered significant at p ⩽ 0.01.     

Dynamic mechanical thermal analysis studies of polymer films prepared from aqueous dispersion

Dynamic Mechanical Thermal Analysis of cast and sprayed films of an aqueous dispersion of polymethyl methacrylate (Eudragit NE30D) and mixtures with an aqueous dispersion of ethylcellulose (Aquacoat ECD-30) has been undertaken. Such analysis allows the identification of glass transition temperatures and the degree of miscibility of the polymers. It was found that the two polymers formed as cast or sprayed films were not miscible but had an optimal composition of 30% of the ethylcellulose dispersion in the polymethyl methacrylate dispersion.     

Influence of magnesium stearate on the physicochemical and pharmacodynamic characteristics of insulin-loaded Eudragit entrapped mucoadhesive microspheres

Abstract

Effective oral insulin delivery has remained a challenge to the pharmaceutical industry. This study was designed to evaluate the effect of magnesium stearate on the properties of insulin-loaded Eudragit® RL 100 entrapped mucoadhesive microspheres. Microspheres containing Eudragit® RL 100, insulin, and varying concentrations of magnesium stearate (agglomeration-preventing agent) were prepared by emulsification-coacervation method and characterized with respect to differential scanning calorimetry (DSC), morphology, particle size, loading efficiency, mucoadhesive and micromeritics properties. The in vitro release of insulin from the microspheres was performed in simulated intestinal fluid (SIF, pH 7.2) while the in vivo hypoglycemic effect was investigated by monitoring the plasma glucose level of the alloxan-induced diabetic rats after oral administration. Stable, spherical, brownish, mucoadhesive, discrete and free flowing insulin-loaded microspheres were formed. While the average particle size and mucoadhesiveness of the microspheres increased with an increase in the proportion of magnesium stearate, loading efficiency generally decreased. After 12?h, microspheres prepared with Eudragit® RL 100: magnesium stearate ratios of 15:1, 15:2, 15:3 and 15:4 released 68.20?±?1.57, 79.40?±?1.52, 76.60?±?1.93 and 70.00?±?1.00 (%) of insulin, respectively. Reduction in the blood glucose level for the subcutaneously (sc) administered insulin was significantly (p?≤?0.05) higher than for most of the formulations. However, the blood glucose reduction effect produced by the orally administered insulin-loaded microspheres prepared with four parts of magnesium stearate and fifteen parts of Eudragit® RL 100 after 12?h was equal to that produced by subcutaneously administered insulin solution. The results of this study can suggest that this carrier system could be an alternative for the delivery of insulin.     

醋酸纤维素水分散体的制备及性质测定

目的:制备醋酸纤维素(CA)水分散体,并测定其部分理化性质。方法:以乙酸乙酯、无水乙醇为溶剂,十二烷基硫酸钠为乳化剂,采用乳化-溶剂挥干法制备醋酸纤维素水分散体,并以沉降体积比评分为指标,通过正交实验,对结果进行直观分析和方差分析,确定了最优处方。结果:最优处方中十二炕基硫酸钠、乙醇和CA的含量分别为3 g·L-1,5％和5％,本法制得的醋酸纤维素水分散体外观良好,平均粒径162 nm,zeta电位-58．8 mV,固形物含量为8．8％,黏度为(5．2±0．7)mPa·s(n=6)。结论:自制的醋酸纤维素水分散体粒径小、固形物含量高、黏度低,能够满足包衣要求。     

Organic solvent-free polymeric microspheres prepared from aqueous colloidal polymer dispersions by a w/o-emulsion technique

Polymeric microspheres were prepared from water-insoluble polymers by a novel technique without the use of organic solvents. Aqueous colloidal polymer dispersions (latexes or pseudolatexes) were emulsified into a heated external oil phase to form a w/o emulsion. The colloidal polymer particles fused (coalesced) into homogeneous polymeric microspheres at temperatures above the minimum film formation temperature upon removal of water. The formation of the microspheres was affected by the glass transition temperature of the polymer, the type of oil and surfactant, the heating temperature and time, and the addition of plasticizers. Plasticizers had to be added to colloidal dispersions with high minimum film formation temperatures. The resulting microspheres were spherical with a smooth surface and non-agglomerated. The particle size could be varied between 5 and 250 μm. Water-soluble compounds such as propranolol HC1 could be entrapped with drug loadings up to 40% within the microspheres by dissolving the drug in the aqueous polymer dispersion prior to the emulsification step. The drug release was sustained over a 6-h period with microspheres prepared with the acrylic pseudolatex, Eudragit RS 30D.     

Influence of Plasticization Time,Curing Conditions,Storage Time,and Core Properties on the Drug Release from Aquacoat-Coated Pellets

Theophylline or chlorpheniramine maleate pellets were coated with an aqueous ethylcellulose dispersion, Aquacoat. The influence of the plasticization time, curing conditions, storage time, and core properties on the drug release were investigated. The plasticization time (time between plasticizer addition to the polymer dispersion and the spraying process) did not affect the drug release, when the water-soluble plasticizer, triethyl citrate, was used because of its rapid uptake by the colloidal polymer particles. In contrast, with the water-insoluble plasticizer, acetyltributyl citrate (ATBC), plasticization time (1/2 h vs 24 h) influenced the drug release, the longer plasticization time resulted in a slower drug release because of a more complete plasticizer uptake prior to the coating step. However, a thermal aftertreatment of the coated pellets at elevated temperatures (curing step) reduced/eliminated the effect of the plasticization time with ATBC. In general, curing reduced the drug release and resulted in stable drug release profiles. The time period between the coating and the curing step was not critical when the pellets were cured for a longer time. The structure of the pellet core (high dose matrix vs low dose layered pellet) strongly affected the drug release. A slow, zero-order drug release was obtained with high dose theophylline pellets, while a more rapid, first-order release pattern was obtained with low dose theophylline-layered nonpareil pellets.     

The Effect of Plasticizers on Compatibility,Mechanical Properties,and Adhesion Strength of Drug-Free Eudragit E Films

The use of plasticizers to affect the properties of drug-free, self-adhesive Eudragit E-100 films with higher transparency was tested for possible transdermal drug delivery. Triacetin was found to be an effective first plasticizer for Eudragit E-100 polymer. In order to improve the flexibility and adhesiveness of Eudragit E-100 film plasticized with triacetin, a more flexible and adhesive, secondary plasticizer was added. Plasticizer–polymer compatibility was evaluated by measuring transparency, surface topography, and solubility. Secondary plasticizers with a low molecular weight and a solubility parameter similar to that of Eudragit E-100 polymer and triacetin were compatible. Further, a lower molecular weight or higher concentration of the secondary plasticizers might lead to greater plasticizing action, reduce tensile strength, and increase film elongation, independent of the hydrophilicity of the plasticizer. The adhesive strength of Eudragit E-100 film under a 180° peel test was also affected by the molecular weight and solubility parameter of the secondary plasticizers used. The results indicate that PEG 200, propylene glycol, diethyl phthalate, and oleic acid can serve as a secondary plasticizer to improve the transparency, flexibility, and adhesion of Eudragit E-100 film.     

Physicochemical and cell adhesion properties of chitosan films prepared from sugar and phosphate-containing solutions.

This work was aimed at investigating a series of chitosan films obtained from chitosan, chitosan-phosphate, chitosan-phosphate-D-(+)raffinose or chitosan-phosphate-D-(+)sucrose solutions to preliminarily select a suitable biomaterial for developing a cell substrate for tissue engineering. The prepared films were characterized in terms of physicochemical properties (FT-IR, XRD, optical microscopy, wettability, water absorption, and tensile stress) and effects on proliferation of different types of human cells (endothelial, HUVEC; fibroblast, WI-38). The obtained results indicated that the presence of sucrose or raffinose at high concentration along with phosphate salts in the chitosan film-forming solution affords smooth, amorphous and highly hydrophilic materials in the form of soft and elastic film with optimal cytocompatibility. Owing to improved physicochemical and mechanical properties as well as affinity for differentiated human cells, these novel chitosan films appear as promising candidate biomaterials for tissue regeneration and repair. The major finding is the possibility to improve the biocompatibility of chitosan films by simply modifying their solid state characteristics.     

Equilibrium and release properties of aqueous dispersions of non-steroidal anti-inflammatory drugs complexed with polyelectrolyte eudragit e 100

Equilibria and release properties of aqueous systems consisting of a set of five non-steroidal anti-inflammatory drugs (AH) complexed with the cationic polymethacrylate Eudragit E 100 (EU) are reported in this study. The composition (EU(AH)(50) (HCl)(50)) having fifty mole percent of each counterion (A(-) and Cl(-)) produces clear, stable aqueous dispersions in which a remarkably high proportion of AH (higher than 98%) is condensed with the PE under the form of ion pairs. This property expands the interval of pH in which AH are aqueous soluble. The set of AH contains members with and without an alpha methyl group (-(CH(3))CH-COOH: Flurbiprofen, Naproxen, Ketoprofen) and (-CH(2)-COOH: Diclofenac, Indomethacin). The proportion of ion pairs in the complexes was lower in the former group. Release of AH from the complexes toward a saline (NaCl 0.9%) solution was assayed in Franz cells. The five complexes behaved as drug carriers that exhibited a slow drug release with a remarkable zero order. In line with the percentages of counterionic condensation observed, release rates from -(CH(3))CH-COOH complexes were clearly higher than those of -CH(2)-COOH ones.     

Penciclovir solubility in Eudragit films: a comparison of X-ray, thermal, microscopic and release rate techniques

The solubility of penciclovir (C₁₀N₅O₃H₁₇) in a novel film formulation designed for the treatment of cold sores was determined using X-ray, thermal, microscopic and release rate techniques. Solubilities of 0.15–0.23, 0.44, 0.53 and 0.42% (w/w) resulted for each procedure. Linear calibration lines were achieved for experimentally and theoretically determined differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) data. Intra- and inter-batch data precision values were determined; intra values were more precise. Microscopy was additionally useful for examining crystal shape, size distribution and homogeneity of drug distribution within the film. Whereas DSC also determined melting point, XRPD identified polymorphs and release data provided relevant kinetics.