Preparation of microcapsules with self-microemulsifying core by a vibrating nozzle method

Incorporation of drugs in self-microemulsifying systems (SMES) offers several advantages for their delivery, the main one being faster drug dissolution and absorption. Formulation of SMES in solid dosage forms can be difficult and, to date, most SMES are applied in liquid dosage form or soft gelatin capsules. This study has explored the incorporation of SMES in microcapsules, which could then be used for formulation of solid dosage forms. An Inotech IE-50?R encapsulator equipped with a concentric nozzle was used to produce alginate microcapsules with a self-microemulsifying core. Retention of the core phase was improved by optimization of encapsulator parameters and modification of the shell forming phase and hardening solution. The mean encapsulation efficiency of final batches was more than 87%, which resulted in 0.07% drug loading. It was demonstrated that production of microcapsules with a self-microemulsifying core is possible and that the process is stable and reproducible.     

Preparation and evaluation of celecoxib-loaded microcapsules with self-microemulsifying core

The purpose of this study was to prepare alginate microcapsules with a self-microemulsifying system (SMES) containing celecoxib in the core. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to prepare the microcapsules. The encapsulated SMES was shown to increase celecoxib solubility over that of the pure drug more than 400-fold. Microcapsules prepared with a high SMES:celecoxib ratio exhibited distinct core vesicles containing liquid SMES. By modifying the SMES and including an additional chitosan coating, drug loading in the range from 12–40% could be achieved with the degree of encapsulation ranging from 60–82%. Alginate microcapsules loaded with SMES and celecoxib showed increased dissolution rate of celecoxib over that of alginate microcapsules loaded with celecoxib or of the celecoxib alone. Compared to the previous report, drug loading capacity was significantly improved, enabling the formulation of dosage forms which are of suitable size for peroral application.     

High celecoxib-loaded nanoparticles prepared by a vibrating nozzle device

Drug delivery research has resulted in the availability of several enabling technologies for formulating poorly water-soluble compounds. In this study the vibrating nozzle device, originally used for encapsulation of drugs, cells and microorganisms, has been used to formulate nanoparticles (NP) with high loading capacity. Celecoxib was incorporated in NP of polylactic acid (PLA) and poly(lactic-co-glycolic acid) (PLGA) and the influence of polymers, initial drug : polymer ratio and stabilizer concentration on NP size and surface properties, entrapment efficiency, drug loading and in vitro release profile were investigated. NP were in the size range of 230–270 nm, with a polydispersity index less than 0.25 and a spherical shape. The highest celecoxib loading (13% w/w) was obtained at initial ratio celecoxib : Resomer RG 502 (PLA/PGA = 50/50) of 1 : 5 and 0.1% w/w polyvinyl alcohol concentration. Thermal analysis and X-ray diffraction suggested that celecoxib was amorphous or molecularly dispersed in the polymeric matrix. The release profile exhibited an initial burst followed by sustained release. The freeze-dried NP could be completely dispersed on addition of lyoprotectants. The production of NP by the vibrating nozzle device is highly reproducible, time saving, can be performed under aseptic conditions and offers the possibility of scale-up.     

Preparation and in vitro evaluation of an ilomastat microemulsion gel by a self-microemulsifying system

The purpose of this study was to construct a microemulsion gel formulation by a self-microemulsifying system for transdermal topical delivery of ilomastat. The optimum formulations were screened by penetration evaluation in vitro. Ilomastat microemulsion gel was prepared by drawing a ternary phase diagram and Pluronic F127 was added as gel matrix for the formulation. The optimal formulations had wide microemulsion existent field and good self-microemulsifying efficiency. The droplet size was within 100 nm. Statistical comparison of the permeation throughout 24 h showed that the two microemulsion gel preparations of ilomastat provided higher permeation than that of the normal gel which had only a low cumulative amount of ilomastat (6.03 microg x cm(-2)) 24 h after application. Cumulative amount of ilomastat from microemulsion gels A and B was 2.2 times and 1.8 times that of the normal gel at 24 h respectively. These results indicate that the microemulsion gel may be a promising vehicle for topical delivery of ilomastat.     

Preparation of magnetic and pH-responsive chitosan microcapsules via sonochemical method

Magnetic and pH-responsive chitosan microcapsules (MPRCMCs) were prepared by a simple sonochemical method. Superparamagnetic oleic acid modified Fe₃O₄ nanoparticles (OA-Fe₃O₄ NPs) and hydrophobic drugs could be directly loaded into MPRCMCs during sonication. The obtained microcapsules had a well-defined spherical morphology with the average size of 2?μm. The microcapsules showed an excellent magnetic property. In addition, the pH-responsive controlled release of coumarin 6 (C6) from MPRCMCs indicated that the developed microcapsules could be a promising candidate for drugs carriers.     

坎地沙坦酯自微乳软胶囊的制备

目的通过坎地沙坦酯自微乳软胶囊的制备工艺研究,确定其最佳工艺条件。方法采用伪三元相图优化了软胶囊内容物的配方,并制备和优化了载药自微乳软胶囊的工艺。结果内容物以乙酸乙酯为油相,RH40为乳化剂,聚乙二醇400为助乳化剂,且三者最佳配比为9∶14∶7。软胶囊囊壳材料最佳配比为明胶∶甘油∶水=1∶0.5∶1,且评价了坎地沙坦酯自微乳软胶囊的相关特性。结论本工艺简单、稳定、可靠。     

海藻酸微囊的制备与评价

目的:探讨利用气体雾化技术(AAT)制备的脂溶性药物吲哚美辛和水溶性药物对乙酰氨基酚海藻酸微囊的理化特性.方法:采用筛分法测定微囊粒径,紫外分光光度法测定微囊的包封率及载药量,恒重法测定微囊中的含水量.结果:海藻酸钠浓度增加、输送速度增加和氮气压力增加与微囊粒径减小.微囊的包封率和载药量随着药物溶解度的增加而降低.微囊含水量最初随着冷冻干燥时间的延长急剧下降,当下降到一定程度后随着冷冻干燥时间的延长变化不大.结论:采用AAT方法制备海藻酸微囊方法简单,但是水溶性大的药物不宜用此法制备微囊.     

Preparation of polyurea/melamine formaldehyde double-layered self-healing microcapsules and investigation on core fraction

Moisture curing type self-healing microcapsules become more attractive, while instability of active core material crippled the efficiency of self-healing behaviour. Polyurea (PU)/melamine formaldehyde (MF) double-layered self-healing microcapsules containing isophorone diisocyanate (IPDI) core with high and stable core fraction were prepared. The structure, morphology, particle size and distribution were studied with Fourier transform infra-red spectroscopy, optical microscopy, scanning electron microscopy and Mastersizer 3000. The influences of process conditions were investigated to uncover the principle of core fraction and morphology of microcapsules. The core fraction of microcapsules was reduced with the increase of ageing time, and microcapsules prepared with ice-bath, polyetheramine (PEA) and prepolymer of melamine formaldehyde (P-MF) had higher core fraction and better morphology. PEA D230 and 1500?rpm agitation rate were chosen according to optimised trade-offs in the core fraction and morphology of the microcapsules.     

原位聚合法制备脲醛树脂微囊的处方工艺研究

目的 确定制备脲醛树脂微囊的最佳处方和工艺,特别是包括抗微囊粘连效果最佳的抗黏剂和添加剂.方法 采用原位聚合一步法制备微囊,考察系统稳定剂种类及用量、多种抗粘剂及添加剂对成囊过程及囊粒粒径的影响.结果 以1.5％PVA作为系统稳定剂,在pH值为3.5、搅拌速度为700r/min的工艺条件下,制备的微囊粒径均匀、不粘连.反应结束后调节系统pH值为7,加入固化剂间苯二酚和增稠剂黄原胶,具有良好抗粘连效果.结论 系统稳定剂的作用是使芯材形成稳定油滴,促使囊材包覆其表面上,最佳的系统稳定剂可降低囊材自身成核的几率.     

普鲁帕酮微囊的研制

本文以明胶为囊材，采用滴入冻凝法将普鲁帕酮包成微囊。并对其包囊率、主药含量、稳定性、粒径分布及体外溶出度进行了实验研究。     

磺胺嘧啶微囊的研制

用羟丙甲基纤维素邻苯二甲酸酯（ＨＰＭＣＰ）为囊材，将磺胺嘧啶包成微型胶囊，并对微囊的主药含量，及其体外释放进行了研究。结果在人工肠液中累积释放曲线的３个主要参数为Ｔ５０２９．９６±０．０６ｍｉｎ；Ｔｄ３５．２３±０．１５ｍｉｎ；ｍ１．７６±０．０３。     

汉防己甲素自微乳的研制

目的研究汉防己甲素白微乳的制备。方法通过考察汉防己甲素在不同介质中的溶解度,采用伪三元相图法制备汉防己甲素自微乳,利用自微乳化效率和载药量考察,筛选最佳处方。结果汉防己甲素自微乳化制剂的处方为：乳化剂OP-10：异丙醇：油酸：油酸乙酯=4：8：1．5：1．5。结论汉防己甲素自微乳载药量为33．31g·L^-1,处方切实可行,性质稳定。     

Determination of the shell permeability of microcapsules with a core of oil-based active ingredient

An experimental and theoretical methodology is proposed to calculate the permeability of microcapsules that contain a core of oil-based active ingredient. Theoretical analysis is performed considering the polydispersity of the measurable capsule size, which allows the estimation of the permeability polydispersity via three different methods. The models proposed were applied in order to determine the permeability of melamine-formaldehyde microcapsules with hexyl salicylate as core oil. Release experiments were performed with four different co-solvents (ethanol, propan-1-ol, propan-2-ol and 1,3-butanediol) of different concentration. Permeability values were found to be constant, despite a two order magnitude of difference in the solubility concentrations.     

Determination of the shell permeability of microcapsules with a core of oil-based active ingredient

An experimental and theoretical methodology is proposed to calculate the permeability of microcapsules that contain a core of oil-based active ingredient. Theoretical analysis is performed considering the polydispersity of the measurable capsule size, which allows the estimation of the permeability polydispersity via three different methods. The models proposed were applied in order to determine the permeability of melamine-formaldehyde microcapsules with hexyl salicylate as core oil. Release experiments were performed with four different co-solvents (ethanol, propan-1-ol, propan-2-ol and 1,3-butanediol) of different concentration. Permeability values were found to be constant, despite a two order magnitude of difference in the solubility concentrations.     

Preparation of hydrogel hollow particles for cell encapsulation by a method of polyester core degradation

Implantation of encapsulated cells in particles of less than 1 mm (micro-encapsulation) has been proposed as a cell synthesized bio-molecule delivery system. Encapsulation provides immuno-isolation, protecting foreign cells from host immune system while nutrients, oxygen and therapeutic products can diffuse freely across capsule walls. A new method is described for the synthesis of a new family of hollow microparticles for cell encapsulation. Unlike other micro-encapsulation methods, encapsulation in those devices will take place after capsule synthesis, by micro-injection. The microcapsules were prepared by a three-steps original procedure: first, synthesis of a core particle, followed by coating with a layer of epichlorohydrin cross-linked amylo-pectin gel and, finally, selective degradation of the core particle to create the cavity. Initial experiments make use of amylo-pectin cross-linked with trimetaphosphate as core particle material. However, selective degradation was difficult to achieve. In further essays, polyesters were used successfully for the preparation of core particles. Optimizations were carried out and the permeability and morphology of the hollow particles were investigated. The preliminary results show that the new method has the potential to become a standard procedure to obtain hydrogel hollow particles. Moreover, the permeability study seems to be in accordance with specifications for immuno-isolation.     

苦参碱固体自微乳制剂的制备及其评价

目的 制备苦参碱固体自微乳颗粒,并对其进行质量评价.方法 通过固体吸附材料的优选,制备了苦参碱固体自微乳颗粒,建立了HPLC法测定颗粒中苦参碱及其体外溶出度的方法;对溶解后微乳的类型、pH值、Zeta电位、粒径进行研究.结果 选择微粉硅胶与甘露醇质量比2∶1为固体吸附材料,每克苦参碱微乳液需加微粉硅胶0.42 g,微晶纤维素0.21 g,50℃恒温干燥后成淡黄色的苦参碱自微乳颗粒,遇水快速形成澄明的液体,平均粒径79 nm,pH值为7.95,Zeta电位-1.34 mV,载药量23.51 mg/g,45 min内累积溶出94.2％以上.结论 苦参碱固体自微乳的制备工艺简单,制剂稳定,可为水难溶性药物的开发提供一个新方法、新思路.     

Preparation and characterization of quercetin-loaded polymethyl methacrylate microcapsules using a polyol-in-oil-in-polyol emulsion solvent evaporation method

Flavonoids and related compounds exhibit a wide range of useful pharmacological properties but present challenges related to their stability and solubility in commonly available solvents. In this study, polymethyl methacrylate (PMMA) microcapsules were prepared using a novel polyol-in-oil-in-polyol (P/O/P) emulsion solvent evaporation method as a means of stabilizing the flavonoids, using quercetin as a model flavonoid drug. The morphology of the microcapsules was evaluated using a scanning electron microscope, revealing a spherical shape with a smooth surface. The cross-section image of the PMMA microcapsules prepared with an amphiphilic polymer in the inner polyol phase showed that the microcapsule was filled with several submicron microspheres. The mean diameter varied from 1.03+/-0.12 microm to 2.39+/-0.42 microm, and the encapsulation efficiency ranged from 12.7% to 26.9%. When free quercetin was stored at 42 degrees C, the residual quercetin content gradually decreased to 18% over 28 days as a result of oxidation. However, when encapsulated in PMMA microcapsules with an amphiphilic polymer in the inner polyol phase, the residual quercetin content decreased to just 82%. In-vitro release studies indicated a sustained release pattern throughout the 36-h study. The release kinetics of the microcapsules with an amphiphilic polymer followed a diffusion-controlled mechanism and the microcapsule without amphiphilic polymer followed an anomalous diffusion behaviour. This study suggests that the novel P/O/P emulsion solvent evaporation method can be applied to the encapsulation of flavonoids.     

酮咯酸氨丁三醇微囊的研究

目的制备酮咯酸氨丁三醇的海藻酸钠-壳聚糖微囊，对其体外释药特性进行考察。方法采用滴液法制备微囊，以均匀设计优化制备工艺，溶出度测定法考察微囊体外释药特性。结果80％微囊粒径在200-250μm，微囊表面光滑圆整无粘连，包封率达90．56％，载药量达43．65％；微囊在人工胃液和蒸馏水中的释药规律符合Higuchi方程。结论酮咯酸氨丁三醇的海藻酸钠-壳聚糖微囊在人工胃液和蒸馏水中具有缓释作用。     

Preparation of microspheres and microcapsules by interfacial polycondensation techniques

A methodological review of the production of microspheres/microcapsules by interfacial polycondensation is presented and the mechanisms of particle and capsule formation are discussed. Procedures for interfacial polycondensation employed for the preparation of microspheres/microcapsules involve the polycondensation of two complementary monomers in a two phase suspension system. Each of the two complementary monomers resides largely in one of the two immiscible phases in the suspension system. The resulting polycondensate, which is formed at or on one side of the interface, may, or may not, be soluble in the droplet phase. If the polymer is soluble in the droplets, particulate microspheres or monolithic microcapsules are formed, i.e. particle forming interfacial polycondensation. If the polymer is insoluble in the droplets, it forms a membrane around them, and the droplets are thus individually encapsulated by the polymer. This leads to the formation of capsular microspheres or reservoir microcapsules, and hence capsule forming interfacial polycondensation. A major example of particle forming interfacial polycondensation is that of phosgene with bisphenol A recently developed for the production of polycarbonate resins in particle form. Capsule forming interfacial polycondensation is widely used to prepare polyamide (nylon) microcapsules containing proteins, pharmaceuticals, etc.     

Preparation of serum albumin microcapsules

Simple coacervation of bovine serum albumin was studied to prepare biodegradable microcapsules. Three types of microcapsules, which differed in shape, were obtained by changing either core size or the bovine serum albumin concentrations of the coacervating systems. Mononuclear microcapsules were prepared by using spherical poly(acrylonitrile) beads as a core material.