Chitosan microspheres in novel drug delivery systems

The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems.     

阿奇霉素微囊的制备与质量控制

目的:制备阿奇霉素微囊,并建立其质量控制方法。方法:以明胶为囊材,阿奇霉素为主药制备微囊。采用紫外分光光度法于482nm波长处测定阿奇霉素的含量,同时考察微囊的形态、粒径、载药量、包封率等指标。结果:所制微囊呈圆形,粒径均匀,平均体积径为100.96μm,平均载药量为23.8%,平均包封率为(68.72±0.89)%。阿奇霉素检测浓度的线性范围为7.5～52.5mg·L-1,平均回收率为(99.5±1.02)%,RSD=1.03%。结论:该制剂制备工艺可行,含量测定方法简便、可靠。     

维生素D_3微囊的制备及含量测定

目的:制备维生素D3微囊并建立其含量测定方法。方法:采用复凝聚法制备微囊;以高效液相色谱法测定维生素D3含量。结果:所制微囊粒径分布均匀,平均粒径(103.9±26.2)μm,包封率(90.8±2.68)%;维生素D3检测浓度的线性范围为0.1～1.0μg.mL-1(r=0.9993),平均回收率为98.65%,45min溶出度为75%以上。结论:该法成功制得维生素D3微囊,所建立的含量测定方法简便可行。     

10-羟基喜树碱的聚赖氨酸/海藻酸钠微胶囊的制备及其体外释药特性研究

目的制备10-羟基喜树碱(HCPT)缓释微胶囊,测定其包封率,并考察其体外释药特性。方法以生物相容性良好的聚赖氨酸和海藻酸钠为囊壁材料,HCPT药物微粒为囊芯,采用静电吸引层层纳米自组装技术(LBL法)制备HCPT微胶囊。结果 LBL法制备的HCPT微胶囊用扫描电子显微镜和激光共聚焦显微镜观察具有明显的核-壳结构;HCPT微胶囊的包封率较高,达到(68.41±0.72)%;随着包裹层数的增加,HCPT微胶囊在体外释放速率降低。结论用LBL法制备的HCPT微胶囊具有较高的包封率和缓释特性,具有一定的应用前景。     

胃漂浮型缓释甲硝唑微囊的研制

以乙基纤维素和3号丙烯酸树脂为主要包囊材料。用液中干燥技术制备了甲硝唑微囊,并对不同制备条件下微囊的形态、释药率、漂浮能力及包封率进行了考察。以本法制得的微囊具有缓释性,能稳定漂浮于人工肠液中6h以上,8h累积释药率达90％,有较好重现性。     

壳聚糖－海藻酸盐微囊对药物的缓释作用

制备了壳聚糖－海藻酸盐的尼莫地平微囊，并研究了它对药物的释放性能。结果表明，该微囊具有缓释作用。     

Double-Layered Polymer Microcapsule Containing Non-Flammable Agent for Initial Fire Suppression

Fire in energy storage systems, such as lithium-ion batteries, has been raised as a serious concern due to the difficulty of suppressing it. Fluorine-based non-flammable agents used as internal substances leaked through the fine pores of the polymer outer shell, leading to a degradation of fire extinguishing performance. To improve the durability of the fire suppression microcapsules and the stability of the ouster shell, a complex coacervation was used, which could be microencapsulated at a lower temperature, and the polymer shell was coated with urea-formaldehyde (UF) resin. The outermost UF resin formed elaborate bonds with the gelatin-based shell, and thus, the structure of the outer shell became denser, thereby improving the loss resistance of the inner substance and thermal stability. The double-layered microcapsules had an average particle diameter of about 309 μm, and a stable outer shell formed with a mass loss of 0.005% during long-term storage for 100 days. This study confirmed that the double-layered microcapsules significantly improved thermal stability, resistance to core material loss, core material content and fire suppression performance compared to single wall microcapsules. These results indicated that the double-layered structure was suitable for the production of microcapsules for initial fire suppression, including highly volatile non-flammable agents with a low boiling point.     

齐墩果酸微囊的制备及质量考察

[目的]制备齐墩果酸微囊并进行质量考察.[方法]采用单凝聚法制备齐墩果酸微囊,并用紫外分光光度法在210 nm波长下测定其药物含量和溶出度.[结果]齐墩果酸在4～120 μg/mL浓度范围呈线性关系(r=0.9999),样品中齐墩果酸含量为12.1%(RSD=0.852%),其平均回收率为99.72%(RSD=1.04%).另外齐墩果酸微囊在30 min时溶出度为(68.2±1.13)%,而普通硬胶囊剂的溶出度为(18.7±1.22)%(P＜0.01).[结论]齐墩果酸微囊制备方法简单,可显著提高齐墩果酸的体外溶出度.     

An injection depot formulation of buprenorphine: extended bio-delivery and effects

AIM: Buprenorphine is an effective medication for treatment of opioid dependence. An injectable depot formulation of buprenorphine has been developed using biodegradable polymer microcapsule technology. This formulation may offer effective treatment of opioid dependence and enhance treatment delivery while minimizing risks of patient non-adherence or illicit diversion of the medication. This report provides a characterization of the bio-delivery of this injectable depot in humans and of the relationship of drug blood levels to pharmacodynamic indices. METHOD AND PARTICIPANTS: The data are from two studies in which 11 opioid-dependent volunteers each received a single depot injection containing 58 mg of buprenorphine, and include previously unreported detailed plasma concentration data over a 6-week time-course following depot administration and examination of their relationship to pharmacodynamic indices. FINDINGS: Mean plasma buprenorphine increased gradually following depot administration, peaked at 2-3 days with a mean concentration of 1.25 ng/ml and then decreased gradually, approaching undetectable levels (< 0.10 ng/mL) by 6 weeks. There was substantial between-subject consistency in several aspects of buprenorphine bio-delivery, including time to first detectable blood level (4 hours), peak blood level (2 days) and undetectable blood level (6-6.5 weeks). In contrast, there was marked between-subject variability in the magnitude of peak buprenorphine concentrations, ranging from 0.17 to 3.47 ng/ml. Extent of opioid blockade was tested by weekly opioid challenges with 3 mg subcutaneous hydromorphone; subjective response and pupillary constriction were related inversely to both buprenorphine and norbuprenorphine plasma concentrations (r=0.84-0.95). CONCLUSION: The data document that this depot formulation provides effective buprenorphine delivery for several weeks and that effects persist even at fairly low buprenorphine plasma concentrations. Suggestions are offered for further research needed to develop this formulation for clinical use as a detoxification and/or maintenance pharmacotherapy for opioid dependence.     

Synthesis of Polyamide-Based Microcapsules via Interfacial Polymerization: Effect of Key Process Parameters

Polyamide microcapsules have gathered significant research interest during the past years due to their good barrier properties; however, the potential of their application is limited due to the fragility of the polymeric membrane. Fully aliphatic polyamide microcapsules (PA MCs) were herein prepared from ethylene diamine and sebacoyl chloride via interfacial polymerization, and the effect of key encapsulation parameters, i.e., monomers ratio, core solvent, stirring rate and time during the polymerization step, were examined concerning attainable process yield and microcapsule properties (shell molecular weight and thermal properties, MC size and morphology). The process yield was found to be mainly influenced by the nature of the organic solvent, which was correlated to the diffusion potential of the diamine from the aqueous phase to the organic core through the polyamide membrane. Thus, spherical microcapsules with a size between 14 and 90 μm and a yield of 33% were prepared by using toluene as core solvent. Milder stirring during the polymerization step led to an improved microcapsule morphology; yet, the substantial improvement of mechanical properties remains a challenge.