Influence of the concentration of a gelling agent and the type of surfactant on the rheological characteristics of oleogels

The investigation on the influence of components that contribute diverse degrees of viscosity to the formulations is of great interest in medicines for topical use. It is such the case of a derivative of the cellulose--ethylcellulose--that participates in the formula of the oleogels of olive oil as a gelificant agent. Surfactant agents--Olivem--can also modify the rheological characteristics of oil gels. In this work, it is studied how the variation of the concentration of ethylcellulose (3-5%) notably changes the viscosity of the prepared ones. The most concentrated preparations in gelling agent are the most viscous and also present a plastic material, whereas the minor concentration awards a Newtonian character to the prepared ones. On the other hand, the influence of the temperature has been investigated--25 and 37 degrees C--verifying that the viscosity of the samples diminishes with the increase of temperature. The influence of the addition of surfactant products--Olivem 900, 700 and 300--has given a result that prepared with major viscosity are those which include Olivem 900 that can be qualified like plastic. The most fluid prepared are those which have been elaborated with Olivem 300, and their liquid character has been confirmed by rheological measurements--viscometry, oscillometry and creep-recovery. Many applications can be foreseen in pharmaceutical as well as in the cosmetic area where the use of natural vegetable oils as vehicles for drugs is large.     

Development of Novel Nonaqueous Ethylcellulose Gel Matrices: Rheological and Mechanical Characterization

No HeadingPurpose. This study reports the rheological and mechanical characterization of novel non-aqueous ethylcellulose gel matrices intended for topical drug delivery. An attempt was also made to explain the molecular interaction within the gel systems from a molecular conformational approach.Methods. Nonaqueous gel matrices were prepared from three fine particle grades of ethylcellulose and propylene glycol dicaprylate/dicaprate. Continuous and oscillatory shear rheometry was performed using a cone-and-plate rheometer and mechanical characterization was performed using a universal tensile tester.Results. The gel matrices exhibited prominent viscoelastic behaviour, yield stress and thixotropy. Rheological and mechanical properties showed significant upward trends with increased polymeric chain length and polymer concentrations. Good linear correlations were obtained between rheological and mechanical properties. The solvent molecular conformation was found to play a role in affecting the formation of gel networks via intermolecular hydrogen bonding between ethylcellulose polymer chains.Conclusions. Ethylcellulose was successfully formulated as a nonaqueous gel with propylene glycol dicaprylate/dicaprate. The novel nonaqueous gel exhibited rheological profiles corresponding to a physically cross-linked three dimensional gel network, with suitable mechanical characteristics for use as a vehicle for topical drug delivery. Molecular conformation of the solvent was found to influence the molecular interactions associated with formation of ethylcellulose gel networks.     

Effect of viscosity and concentration of wall former, emulsifier and pore-inducer on the properties of amoxicillin microcapsules prepared by emulsion solvent evaporation

This study reports the laboratory optimization for the preparation of sustained release amoxicillin (AMX) ethylcellulose microcapsules by an emulsion solvent evaporation process by adjusting the viscosity and concentration of ethylcellulose, ratio of amoxicillin to ethylcellulose, and concentration of emulsifier and pore inducer. When ethylcellulose with a viscosity of 45 mPa.s was used, almost no material stuck to the inside wall of the beaker and uniform microcapsules were prepared. The average diameter of microcapsules increased and yield and release rate decreased as the concentration of ethylcellulose increased from 1% to 8%. The release of amoxicillin from microcapsules was influenced by the ratio of the weight of drug to that of ethylcellulose and ratios of 2:1 and 4:1 were most suited for optimum amoxicillin release. The average diameter of microcapsules decreased and the release rate increased as the concentration of the emulsifier increased from 1.5% to 6.0%, however, the size distribution became significantly wider with the increase in the concentration of sorbitan monooleate. Addition of small amounts of a water-soluble agent sucrose improved the release of active ingredient from the microcapsule matrix without influencing the morphology and particulate properties of the microcapsules.     

琥珀酸去甲文拉法辛缓释微丸的制备及释放特性的研究

目的 采用乙基纤维素水分散体(Surelease(R))为包衣材料制备琥珀酸去甲文拉法辛(DVS)缓释微丸,并评价其体外释药性能.方法 采用溶液上药法,在蔗糖空白丸芯的基础上旋转锅包衣法上药,通过正交筛选优化上药工艺,再以Surelease(R)为缓释材料进行包衣,以原研缓释片为参比对微丸的体外释放进行评价,并将释放数据用常用模型拟合,探讨其释放机制.结果 所得缓释微丸的载药量和上药率均较高,含量均匀,当聚合物包衣增重32.4％时可达到与原研缓释片一致的释放特性,在piH1.2、pH4.5、水、pH6.8的释放介质中两者的相似因子分别为86.65、69.94、67.47、67.97,体外释放曲线符合一级方程.结论 制备的DVS缓释微丸具有较理想的缓释效果.     

喷雾干燥法制备对乙酰氨基酚缓释微球

目的 利用喷雾干燥法制备对乙酰氨基酚缓释微球,并考察其释放度.方法 以对乙酰氨基酚为模型药、乙基纤维素为载体材料、95 %乙醇为溶剂进行喷雾干燥而制备.结果 所制微球外观为圆整球形,粒度分布均匀,其体外释放度1 h时不少于15 %,2 h不超过40 %,12 h在90 %以上;在pH6.8的磷酸盐缓冲液中可缓慢并稳定地释放.经大鼠体内药物动力学研究表明,微球具有明显的缓释效果.结论 所制微球具有很好的缓释作用,操作方便,工艺稳定,有利于工业化生产.     

载有酮洛芬-乙基纤维素缓释固体分散体的海藻酸钙小珠的制备

目的:制备酮洛芬-乙基纤维素固体分散体并将其包载于海藻酸钙小珠中,以期制备酮洛芬缓释微丸制剂.方法:采用一种新的溶剂萃取共沉淀法制备固体分散体,差示扫描量热法进行固体分散体物相分析;离子胶凝法将固体分散体包载进海藻酸钙小珠,扫描电子显微镜分析其形态,并考察其体外释药特性.结果:差示扫描量热分析证实药物以非晶型分散于载体中,较低的药物损失率和简便操作证明这种制备方法是可行的,固体分散体具有缓释效果,使用海藻酸钙小珠包载后,降低了在释放介质中的突释性.结论:本方法制备酮洛芬-乙基纤维素缓释固体分散体可行,海藻酸钙包载后降低了释放介质中的突释.     

Use of fine particle ethylcellulose as the diluent in the production of pellets by extrusion-spheronization

The effect of small ethylcellulose particle size on the manufacture and properties of pellets produced by extrusion-spheronization was investigated. A factorial design revealed the effects of microcrystalline cellulose (MCC), polyethylene oxide (PEO), water, and spheronization speed and time on pellet properties. Response surface modeling allowed optimization of the responses with expansion to a central composite design. Pellet yield, size, shape, friability and drug release profile were studied, along with surface and interior morphology. Pellets were spherical irrespective of the formulation and process variables and exhibited physical and mechanical characteristics appropriate for further processing. Yield in the 12/20 mesh cut was lower with FPEC than observed with coarse particle ethylcellulose (CPEC), but FPEC-containing pellets were more rugged and the PEO to obtain optimal pellets was lower for FPEC compared to CPEC. Immediate release products were obtained and ethylcellulose particle size was of no consequence to drug release. Observed responses for the optimized product agreed with predicted values, demonstrating the success of the optimization procedure. These results suggest that FPEC is a good diluent for extrusion-spheronization.     

Colon targeting with bacteria-sensitive films adapted to the disease state

The aim of this study was to identify novel polymeric films allowing for the site-specific delivery of drugs to the colon of patients suffering from inflammatory bowel diseases. Ethylcellulose was blended with different types of bacteria-sensitive starch derivatives. The water uptake and dry mass loss kinetics of the systems were monitored upon exposure to media simulating the contents of the stomach, small intestine and colon (including fresh fecal samples from Crohn’s Disease and Ulcerative Colitis patients). Importantly, ethylcellulose:Nutriose FB 06 and ethylcellulose:Peas starch N-735 films showed highly promising water uptake and dry mass loss kinetics in all the investigated media, indicating their potential to minimize premature drug release in the upper gastro-intestinal tract, and allowing for controlled release once the colon is reached. This can be attributed to the fact that the starch derivatives serve as substrates for the enzymes, which are secreted by the bacteria present in the colon of inflammatory bowel disease patients. Thus, the identified new polymeric films are adapted to the pathophysiological conditions in the gastro-intestinal tract in the disease state. Furthermore, Nutriose is known to provide pre-biotic effects, which can be of great benefit for these patients.     

Micronized ethylcellulose used for designing a directly compressed time-controlled disintegration tablet

Ethylcellulose (EC) of varying particle sizes has been used as an outer coating layer to design a novel dry-coated tablet with time-controlled drug release. This dry-coated tablet, containing a core tablet of sodium diclofenac and an outer coating layer of EC, was prepared by direct compression. The drug release from dry-coated tablet exhibited an initial lag period that was dependent on the particle size of the EC powder, followed by a stage of rapid drug release. The smaller the EC particle size used the longer the lag time obtained, suggesting the particle size of EC powder could modulate the timing of drug release from such a dry-coated tablet. The period of the lag time for sodium diclofenac released from dry-coated tablets was correlated with the penetration distance of the solvent into dry-coated tablet by an in vitro dye penetration study. The densest packing of EC powders appeared on the upper and lower surfaces of dry-coated tablet after compression, resulting in a tight structure yielding a slower penetration of the solvent. Whereas loose packing of EC powders occurred in the middle of the lateral surface of dry-coated tablet, this loosely packed surface readily allowed solvent penetration and that finally caused the splitting of tablet shell into two halves in the dissolution medium. The results suggest that these dry-coated tablets prepared with different particle sizes of EC powder as an outer coating layer might offer a desirable release profile for drug delivery at the predetermined times and/or sites.     

肝动脉栓塞米托蒽醌乙基纤维素微球的制剂学研究

利用正交实验设计法优选适用于肝动脉栓塞的米托蒽醌乙基纤维素微球制备条件和工艺，采用动态透析法模拟体内情况研究了该微球的体外释药规律；根据混悬液的稳定性理论，优选并制备了适于临床肝动脉介导栓塞使用的米托蒽醌乙基纤维素微球混悬注射液。结果表明：在优化工艺条件下制得的米托蒽醌乙基纤维素微球外观圆整，球径在４０～１５０μｍ范围内的占总数的８６．５％，平均球径为１１０．２４±３８．１９μｍ；包封率为５５．６％；载药量为１２．５％，体外释药符合单指数模型，释药方程为ｌｏｇ（Ｙ∞－Ｙ）＝－０．１１６ｔ－１．１９８×１０（－３）（ｒ＝０．９９９２，ｔ（５０）＝２．６ｈ）；其混悬注射液理化性质稳定，可适于临床应用。