Influence of polymers on the bioavailability of microencapsulated celecoxib

Celecoxib, a selective COX-2 inhibitor, primarily used in treatment of osteoarthritis, rheumatoid arthritis and acute pain was encapsulated in microparticles composed of various polyesters, polymethacrylates or cellulose derivatives used alone or blended. The influence of polymers on microparticle mean diameter, encapsulation efficiency and in vitro and in vivo celecoxib release was investigated. Microparticles were in the size range 11–37?µm. Encapsulation efficiency was optimal due to poor aqueous solubility of celecoxib. Considering in vitro release, microparticles could be divided into drug delivery systems with fast and slow release profiles. Microparticles prepared with poly-ε-caprolactone, Eudragit® RS and low viscosity ethylcellulose, together with physical mixture of celecoxib with lactose and Celebrex®, were tested in vivo. Relative bioavailability of celecoxib was below 20% in all cases and was probably the consequence of a slow in vivo release of celecoxib from microparticles or low wettability in the case of Celebrex® and physical mixture.     

Poly (ε-caprolactone) microparticles containing Levobunolol HCl prepared by a multiple emulsion (W/O/W) solvent evaporation technique: Effects of some formulation parameters on microparticle characteristics

Abstract

The aim of this study was to prepare poly (ε-caprolactone) (PCL) microparticles of Levobunolol HC1 (L-HC1) for use as an anti-glaucomatous drug to the eye. The double emulsion (W/O/W) solvent evaporation technique was used for encapsulating L-HC1 as a hydrophilic drug. The study examined the impact of different factors including the pH and volume of the external aqueous phase, the concentration of polyvinylalcohol (PVA) and pluronic® F68 (PF68) used as stabilizers and drug/polymer ratios on the characteristics of the microparticles. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were used to identify the physical state of the drug and polymer. The zeta potential of the particles was also identified. Entrapment efficiency was found to be highest with a 0.5% PVA concentration and 100 mL volume of external aqueous phase at pH 12. The high efficiency was due to a reduction in the degree of drug ionization. The microparticles were spherical and appropriately sized for ophthalmic application. Drug release from the microparticles appears to consist of two components, with an initial rapid release followed by a slower stage. Drug release was slower when the microparticle was incorporated into the thermally reversible gel (Pluronic® F127) in comparison to drug release from the free drug incorporated into the gel and drug release from the free microparticle.     

Microencapsulation with carrageenan-locust bean gum mixture in a multiphase emulsification technique for sustained drug release

Abstract

A multiphase emulsification technique was modified in this process of microencapsulating gentamicin sulphate, thus avoiding the necessity for a surfactant in preparing the secondary emulsion for a W/O/W emulsion. Various proportions of iota-carrageenan (i-C) and locust bean gum (LBG) were investigated for the W/O/W emulsion after forming the primary W/O emulsion with sorbitan trioleate, Span 85. Upon removal of the oil phase (chloroform) from the W/O/W emulsion by heating (60-65°C), microcapsules or ‘W/W particles containing drug dissolved in sodium hyaluronate were spontaneously formed. These were dispersed in a solution of a mixture of 5-10 per cent w/v polyvinyl alcohol, PVA (average MW 50000-106000; 98 per cent hydrolysed) and 3 per cent v/v polyethylene glycol 200 (PEG 200), and dried to form the hydrogel film casts. Our in vitro experiments in isotonic phosphate buffer solution (pH 7-4) at 37°C., showed that the release of gentamicin sulphate was dependent on concentration of LBG, and concentration or molecular weight of PVA. With the exception of PVA hydrogel matrix preparations containing 20 per cent w/v LBG, all other formulations showed a significant initial ‘burst' release of drug within 6h. The drug-containing microcapsules in the PVA hydrogel film with 20 per cent w/v LBG, exhibited an almost zero-order release of drug up to 140h. It is postulated that an effective barrier or high-density membrane enveloping the microcapsules was formed between i-C and LBG because of their unique molecular configurations. This phenomenon, together with the possible adsorption of i-C molecules at the transient oil and outer aqueous phase interface, presumably eliminated the need for a permanent oil phase and/or an O/W surfactant normally required for preparing W/O/W emulsions.     

In vivo and in vitro characteristics for insulin-loaded PLA microparticles prepared by w/o/w solvent evaporation method with electrolytes in the continuous phase

Insulin-loaded poly(lactide) (PLA) microparticles were successfully prepared by 6% w/v PLA in the organic phase, 10% w/v PVP and varied types of 5%w/v electrolytes in the continuous phase, by using a water-in-oil-in-water emulsion/solvent extraction technique. Addition of electrolytes such as NaCl, CaCl₂ into the external phase significantly improved insulin entrapment efficiency compared to the case of no additives. NaCl was the most effective for obtaining high entrapment efficiency, with microparticle yield 81.2%, trapping efficiencies 49%, insulin-loading level 5.5% w/w and mean particle size 14.8?µm. The distribution (%) of insulin on the PLA microparticles surface, outer layer and core were 8, 37 and 43%, respectively. The cumulative release of insulin had an upper limit of ～24% of the insulin load at 24 days. A steady release rate was 0.5?µg insulin/mg microparticles/day of insulin release maintained for 24 days. Total protein-leaking amount was reduced after addition of electrolytes in the continuous aqueous phase. Rabbit glucose levels were evaluated after subcutaneous 20?mg insulin-loaded PLA microparticles or PLA blank microparticles. Study results show that the insulin-loaded PLA microparticles significantly reduced the glucose level than PLA blank microparticles. The insulin-loaded PLA microparticles, physicochemical characterization data and the animal result obtained in this study may be relevant in optimizing the PLA microparticle formulation incorporation and delivery insulin carriers.     

Polymer encapsulation of amoxicillin microparticles by SAS process

Abstract

Encapsulation of amoxicillin (AMC) with ethyl cellulose (EC) by a supercritical antisolvent process (SAS) was investigated. AMC microparticles obtained previously by an SAS process were used as host particles and EC, a biodegradable polymer used for the controlled release of drugs, was chosen as the coating material. In this work, a suspension of AMC microparticles in a solution of ethyl cellulose in dichloromethane (DCM) was sprayed through a nozzle into supercritical CO₂. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and HPLC analyses were carried out. The effects of AMC:EC ratio, the initial polymer concentration of the solution, temperature and pressure on the encapsulation process were investigated. Although all the experiments led to powder precipitation, the AMC encapsulation was achieved in only half of the cases, particularly when the lower drug:polymer ratios were assayed. In general, it was observed that the percentages of AMC present in the precipitates were higher on increasing the AMC:EC ratio. In these cases composites rather than encapsulates were obtained. The in vitro release profiles of the resulting materials were evaluated in order to ascertain whether composites can be used as encapsulated systems for drug delivery systems.     

留学生心内科见习带教的实践体会

临床见习是医学院校留学生临床教学的重要组成部分,针对其特点,选择一批业务水平高、英语能力强的医师和在读博士担任教学工作。课前制定教学计划,进行语言准备,设计完成教案,选择好病例;见习中从小节抓起,采用PBL教学法,重视病史采集和体格检查的教学,重视临床思维能力等的培养;最后就见习中存在的问题提出了一些建议。     

胃癌患者内皮细胞微颗粒的检测及其意义

目的比较胃癌患者与正常对照组血浆中内皮细胞微颗粒（EMPs）、血管性血友病因子（vWF）水平的变化,探讨EMPs检测在胃癌中的意义。方法采用流式细胞术及酶联免疫吸附试验（ELISA）检测68例胃癌患者和20例正常对照者血浆中EMPs、vWF的水平,分析这些指标与临床特征的关系。结果胃癌患者血浆vWF及EMPs水平显著高于正常对照组（P〈0.01）,血浆vWF及EMPs水平Ⅲ、Ⅳ期患者高于Ⅰ、Ⅱ患者（P〈0.01）,有淋巴结及肝转移者高于无淋巴结及肝转移者（P〈0.01）,有静脉浸润者高于无静脉浸润者（P〈0.01）,浸润至肌层、浆膜层者高于浸润至黏膜或黏膜下层者（P〈0.01）。结论血浆EMPs可准确反映内皮功能,内皮功能紊乱参与胃癌的转移过程,EMPs可作为判断胃癌的病情、预后、疗效的指标之一。     

Spray drying from organic solvents to prepare nanoporous/nanoparticulate microparticles of protein: excipient composites designed for oral inhalation

Objectives The aim of this study was to determine if spray‐drying could successfully produce microparticles containing the model protein trypsin in a form suitable for inhalation. Methods Trypsin was spray‐dried with raffinose from a methanol : n‐butyl acetate solvent system (MeOH : BA). The solvent system was then adjusted to include water, and trypsin was co‐spray‐dried with raffinose, trehalose or hydroxpropyl‐β‐cyclodextrin. The spray‐dried products were characterised by SEM, XRD, DSC, TGA and FTIR. Protein biological activity and in‐vitro deposition of trypsin : excipient nanoporous/nanoparticulate microparticles (NPMPs) was also assessed. Key findings The inclusion of water in a MeOH : BA solvent system allowed for the successful production of NPMPs of trypsin : excipient by spray‐drying. Trypsin formulated as trypsin : excipient NPMPs retained biological activity on processing and showed no deterioration in activity or morphological characteristics when stored with desiccant at either 4 or 25°C. Hydroxpropyl‐β‐cyclodextrin showed advantages over the sugars in terms of producing powders with appropriate density and with greater physical stability under high‐humidity conditions. Fine particle fractions of between 41 and 45% were determined for trypsin : excipient NPMPs. Conclusions NPMPs of trypsin : excipient systems can be produced by spray‐drying by adjustment of the solvent system to allow for adequate solubility of trypsin.     

幽门螺杆菌根除前后对CagA~+冠心病患者血管内皮功能的影响

目的:探讨幽门螺杆菌(Hp)根除前后细胞毒素相关基因A阳性(CagA+)对冠状动脉粥样硬化性心脏病(冠心病)患者血管内皮功能的影响。方法:选择Hp+CagA+冠心病患者57例为根除治疗组,同期住院的57例Hp-CagA-冠心病患者为对照组。在常规治疗的基础上,根除治疗组接受根除Hp治疗,对照组接受安慰剂治疗,研究期为6个月。两组研究对象在实验前后接受血脂、外周血循环内皮微颗粒(cEMP)水平及肱动脉对反应性充血的内皮依赖血管扩张反应(FMD)检测。结果:治疗后根除治疗组患者的血浆总胆固醇、cEMP水平比治疗前明显降低,FMD明显升高(P均<0.05)。治疗前根除治疗组总胆固醇高于对照组(P<0.01),治疗后两组总胆固醇比较差异无统计学意义(P>0.05)。结论:根除Hp+CagA+,可改善合并Hp+CagA+感染冠心病患者的血管内皮功能。