The in vitro evaluation of gelatin coacervate microcapsules

Microcapsules of sulphadiazine have been prepared by the simple gelatin coacervation technique, using sodium sulphate as coacervating agent. The free flowing microcapsular material was hardened with formalin. There is no direct relation between particle size and sulphadiazine concentration nor between different starting gelatin percentages. The effects on size of hardening time, temperature and sampling time are small. In vitro dissolution studies show that first order release characteristics are exhibited by all the hardened materials. Temperature and pH effects indicate the dissolution of the sulphadiazine itself to be the controlling step rather than the rate of diffusion through the microcapsule wall.     

Sustained release and biological availability of dalarelin from the biodegradable coacervate microcapsules

A complex coacervation method was used to prepare microcapsules containing 74.8±1.5% of the ¹²⁵I labelled dalarelin incorporated in the gelatine–algin coating. Microcapsules (62±1.7%) formed, did not exceed a size of 108 μm. The high content of the small size allowed this formulation to be administered by intramuscular injection to rats. It was found that the ¹²⁵I labelled dalarelin in the form of microcapsules had better bioavailability and was active longer in the rat when compared with the ¹²⁵I labelled dalarelin solution injections. Dalarelin administered in the microcapsular form was characterised by a higher biological availability. The degree of relative biological availability was calculated as 123% for the dalarelin in the microcapsular form.     

Sustained release and biological availability of dalarelin from the biodegradable coacervate microcapsules

A complex coacervation method was used to prepare microcapsules containing 74.8 +/- 1.5% of the 125I labelled dalarelin incorporated in the gelatine-algin coating. Microcapsules (62 +/- 1.7%) formed, did not exceed a size of 108 microm. The high content of the small size allowed this formulation to be administered by intramuscular injection to rats. It was found that the 125I labelled dalarelin in the form of microcapsules had better bioavailability and was active longer in the rat when compared with the 125I labelled dalarelin solution injections. Dalarelin administered in the microcapsular form was characterised by a higher biological availability. The degree of relative biological availability was calculated as 123% for the dalarelin in the microcapsular form.     

In vitro drug release from egg albumin microcapsules

The in vitro release of phenacetin from microcapsules prepared using egg albumin as the membrane material was investigated. It was shown by scanning electron microscopy that the albumin microcapsules have nonsmooth surfaces. The amount of phenacetin released is proportional to the square root of time up to 50-70% drug release. Increases in the albumin concentration and 1-vinyl-2-pyrrolidinone polymer content in the aqueous phases used in the microcapsule preparation have an effect on matrix porosity and channel tortuosity in the matrix of albumin microcapsules. The in vitro release rate was found to decrease with increasing albumin concentration and 1-vinyl-2-pyrrolidinone polymer content in the aqueous phases. The in vitro release rate per unit area also decreased with decreasing capsule size.     

Effect of preparation and storage on drug release from ointments containing the dissolved drug

The drug release from an ointment that contains dissolved drug depends on the kind of preparation and on the time of storage. This indicates a relationship between shear treatment (disruption of the gel matrix) and liberation rate. With increasing storage time of the ointment the liberation rate decreases due to the increasing diffusional resistance of the reforming gel matrix.     

洛伐他汀渗透泵片的制备及体外释药影响因素的考察

目的：制备洛伐他汀渗透泵片，考察片芯组成和包衣膜对药物释放行为的影响，并对处方进行优化。方法：根据不同时间药物累积释放度描述药物的释放行为，采用相异因子（f1）、相似因子（f2）法评价释放曲线的相似性，利用双因素的复合析因设计优化处方。结果：片芯组成（如聚氧乙烯的相对分子质量及用量，渗透压促进剂种类和增溶剂种类）和包衣膜组成（如聚乙二醇的相对分子质量及用量和衣膜增重）对洛伐他汀渗透泵片的体外释药行为有显著影响。依据最优处方制备的洛伐他汀渗透泵片符合以渗透压差为释药动力的释药模式，1-8h内呈现良好的零级释放特征（r=0．9968），其体外释药曲线与同类进口g-在24h内释药行为相似（f1=10．2，f2=79．5）。结论：经优化后制备的洛伐他汀渗透泵制剂释药完全，零级释放特征显著，与同类进口片释药行为相似。     

The effect of surfactants on the microencapsulation and release of phenobarbitone from gelatin-acacia complex coacervate microcapsules

The effects of sodium lauryl sulphate (SLS), cetrimide and polysorbate 20 surfactants at concentrations below, at and above their critical micelle concentration (CMC) on the microencapsulation and release of phenobarbitone have been described. Bimodal particle size distributions were produced both in the absence and presence of each of the three surfactants. The presence of surfactant had little or no effect on the particle size distribution at any given stirring speed. A large variation was noted in the amount of phenobarbitone microencapsulated dependent upon the type of surfactant and its concentration. The amount of phenobarbitone encapsulated decreased with increasing concentration of polysorbate 20 and with SLS. Cetrimide (0.025 per cent w/v) enhanced encapsulation with 2 per cent w/w colloids but higher concentrations at the CMC and above decreased encapsulation. The results are explained in terms of decreased interfacial tension by the surfactant and by steric and electrostatic effects caused by surfactant adsorption onto the coacervate droplets and phenobarbitone particles.     

The effect of surfactants on the microencapsulation and release of phenobarbitone from gelatin-acacia complex coacervate microcapsules

Abstract

The effects of sodium lauryl sulphate (SLS), cetrimide and polysorbate 20 surfactants at concentrations below, at and above their critical micelle concentration (CMC) on the microencapsulation and release of phenobarbitone have been described. Bimodal particle size distributions were produced both in the absence and presence of each of the three surfactants. The presence of surfactant had little or no effect on the particle size distribution at any given stirring speed. A large variation was noted in the amount of phenobarbitone microencapsulated dependent upon the type of surfactant and its concentration. The amount of phenobarbitone encapsulated decreased with increasing concentration of polysorbate 20 and with SLS. Cetrimide (0025 per cent w/v) enhanced encapsulation with 2 per cent w/w colloids but higher concentrations at the CMC and above decreased encapsulation. The results are explained in terms of decreased interfacial tension by the surfactant and by steric and electrostatic effects caused by surfactant adsorption onto the coacervate droplets and phenobarbitone particles.     

替莫唑胺壳聚糖缓释微球的制备及体外释药特性

目的:制备替莫唑胺壳聚糖缓释微球,并对其体外释药模式进行研究.方法:以替莫唑胺为模型药物,采用乳化交联法制备壳聚糖微球,两步优化法优化处方和制备工艺.通过测定微球的粒径及其分布、载药量、包封率和体外释放速度对微球进行质量评价.结果:优化工艺制得的微球平均粒径为(3.9±1.6)μm,载药量为(7.1±0.5)%(n=3),包封率为(25.0±0.8)%(n=3),体外释药特性研究具有良好的缓释特性,在0～8 h符合Higuchi方程,Q=11.717 26.951t1/2(r=0.980),8～24 h符合一级释放曲线,lnQ=4.37 0.007 5t(r=0.983).结论:通过优化处方和制备工艺,采用乳化交联法可制备出以壳聚糖为载体、替莫唑胺为模型药物的缓释微球,其体外释药具有明显的缓释作用.     

卡托普利渗透泵控释片的制备及体外释放度考察

目的研究卡托普利渗透泵控释片的制备工艺及体外释药影响因素。方法以比色法为分析方法 ,采用综合评分法评价体外释放行为。结果卡托普利渗透泵控释片的体外释药符合零级释放规律 ,释药速率受HPMCK1 5含量、渗透压促进剂用量影响较大 ,在一定范围内 ,释药孔大小和片芯硬度对其影响较小 ,与溶出方法、介质 pH值、桨转速无关。 结论体外释放规律符合控释制剂要求 ,可进一步进行体内释药行为考察     

萘普生缓释微囊的制备及其体外释药研究

目的 对以壳聚糖和海藻酸钠为囊材,通过复凝聚法将萘普生微囊化的制备工艺和体外释药进行研究.方法 以微囊的药物包封率为制备工艺优化指标,得出成囊的最佳制备工艺条件.结果 最佳工艺条件为:搅拌速度500 r·min-1,pH4.0,壳聚糖浓度3%,反应温度50℃.结论 以最佳制备工艺条件制备了可生物相容,自然降解无毒的载药微囊,重现性好,工艺稳定,同时体外溶出实验表明,该微囊具有较好的缓释作用.     

Influence of coacervation-inducing agents and cooling rates on the preparation and in vitro release of bleomycin hydrochloride microcapsules

Abstract

Two types of coacervation-inducing agents (EVA, PIB) and three cooling rates (0.01998, 0.03482 and 0.06725d`C/min) affecting the preparation, micromeritic and drug release properties of bleomycin hydrochloride microcapsules were investigated. Particle size distribution of microcapsules induced by EVA significantly depended on the cooling rate, but that induced by PIB was independent of the cooling rate. Higher viscosity of PIB led to a smaller particle size of microcapsules than when EVA was used. The surface topography of the microcapsules for both types of coacervation-inducing agents was obviously different. We found that the release behaviour of bleomycin hydrochloride from the microcapsules also depended on the type of coacervation-inducing agent and the cooling rate. In general, the slower the cooling rate the more prolonged the release of the drug. Higuchi matrix model was followed for bleomycin hydro chloride released from the microcapsules. T₅₀ of both types of microcapsules decreased with the increase of the cooling rate. To simulate the absorption behaviour of the GI tract, the continuous flow dialysis method was modified for drug release from the microcapsules. The data indicate that the diffusion of the dissolution medium and dissolved drug through the ethylcellulose wall of the microcapsules is the rate-limiting step before dialysis. This also implies that the release rate of the drug from dosage form significantly determined the absorption in the GI tract.     

Effect of ethylene-vinyl acetate concentration on ethylcellulose-walled microcapsules: preparation and release kinetics of theophylline microcapsules

The effect of concentration of ethylene-vinyl acetate (EVA) copolymer, used as a coacervation-inducing agent, on the preparation of ethylcellulose microcapsules was studied with theophylline as the core material. The influence of EVA concentration on the micromeritic properties of the microcapsules and their drug release behaviour were investigated. Particle size distribution of the microcapsules obtained was dependent on the amount of EVA copolymer. As the EVA concentration increased the quantity of larger particles was reduced and that of the smaller particles was increased. Thus EVA might be used as a protective colloid to prevent aggregation of the microcapsules. The porosity of the microcapsules decreased with respect to EVA concentration, but the wall thickness of the microcapsules showed a corresponding increase. Zero-order release kinetics, from the resulting microcapsules in the initial dissolution phase was obtained. The apparent zero-order release rate in the initial steady-state decreased with the increase of EVA concentration, but T50 increased. The higher concentration of EVA causing a thick, compact wall lead to an effective prolongation of drug release.     

曲匹地尔缓释片的制备与体外释放度测定

目的:研制曲匹地尔缓释片。方法:用高分子化合物作辅料制备缓释片,测定释放度。结果:该处方、制备工艺简单,体外 释药符合缓释片的规律。结论:曲匹地尔缓释片剂可作为曲匹地尔的新制剂开发。     

Controlled release captopril microcapsules: effect of ethyl cellulose viscosity grade on the in vitro dissolution from microcapsules and tableted microcapsules

Captopril microcapsules were prepared using four different viscosity grades of ethyl cellulose (core: wall ratios 1:1, 1:2 and 1:3) by temperature induced coacervation from cyclohexane. In vitro dissolution studies in 0.1 M hydrochloric acid showed that the drug release was dependent on the core to wall ratio, the viscosity grade of the ethyl cellulose and thus the total viscosity of the coacervation system. Viscosity grade of greater than 100 c.p. was unsuitable for microencapsulation by coacervation method at the concentration used. The surface characteristics of a 1:2 core to wall ratio were studied by scanning electron microscopy. The surface of the microcapsules prepared with 10 c.p. viscosity grade was comparatively more porous with larger size pores than 50 c.p. viscosity grade of ethyl cellulose. However, 300 c.p. viscosity grade showed incomplete wall formation. The microcapsules did not fragment during dissolution, alter in shape or size, or show evidence of enlargement of the surface pores. The tensile strength of tablets prepared at constant pressure from each batch of microcapsules (mean diameter 675 microns) increased as both the core to wall ratios and the viscosity of ethyl cellulose increased. The dissolution rate of the drug from tableted microcapsules was significantly delayed. The in vitro release gave best correlation with first order release kinetics when compared to zero-order and square-root-of-time equations.     

pH-controlled drug loading and release from biodegradable microcapsules

Microcapsules made of biopolymers are of both scientific and technological interest and have many potential applications in medicine, including their use as controlled drug delivery devices. The present study makes use of the electrostatic interaction between polycations and polyanions to form a multilayered microcapsule shell and also to control the loading and release of charged drug molecules inside the microcapsule. Micron-sized calcium carbonate (CaCO3) particles were synthesized and integrated with chondroitin sulfate (CS) through a reaction between sodium carbonate and calcium nitrate tetrahydrate solutions suspended with CS macromolecules. Oppositely charged biopolymers were alternately deposited onto the synthesized particles using electrostatic layer-by-layer self-assembly, and glutaraldehyde was introduced to cross-link the multilayered shell structure. Microcapsules integrated with CS inside the multilayered shells were obtained after decomposition of the CaCO3 templates. The integration of a matrix (i.e., CS) permitted the subsequent selective control of drug loading and release. The CS-integrated microcapsules were loaded with a model drug, bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA), and it was shown that pH was an effective means of controlling the loading and release of FITC-BSA. Such CS-integrated microcapsules may be used for controlled localized drug delivery as biodegradable devices, which have advantages in reducing systemic side effects and increasing drug efficacy.     

Design of prolonged-release microcapsules containing diclofenac sodium for oral suspensions and their preparation by the Wurster process

Prolonged-release microcapsules of diclofenac sodium (DS), an acidic drug, applicable as an oral suspension for twice-a-day administration were designed. The microcapsules with a mass median diameter of around 100 μm and a high drug content were intended to exhibit a preferably prolonged release of highly water-soluble DS when prepared by the Wurster process–a spray coating method using a spouted bed assisted with a draft tube. The microcapsule was composed of a calcium carbonate core of 32–44 μm, a drug-layer of DS, hydroxypropyl cellulose and polyethyleneglycol 6000, an undercoat of Eudragit L30D and a release-sustaining coat of Eudragit RS30D. Eudragit L30D films were undercoated to decrease the solubility of DS within the environment of the microcapsules and thereby to prolong the drug release. This made it possible to decrease the amount of Eudragit RS30D membrane required to prolong the drug release, leading to decrease in the particle size of products and achievement of high drug content. As a result, prolonged release microcapsules with a mass median diameter of 92 μm and a drug content of 29% could be obtained.