Preparation Of Biodegradable Microspheres Research Articles

Effects of chemical and physical parameters in the generation of microspheres by hydrodynamic flow focusing

Hydrodynamic flow focusing is a seminal, easy-to-use technology for micro- and nanodroplet generation. It is characterized by the co-axial focusing of two (or more) immiscible liquid streams forced through a small orifice. In this method, the outer continuous phase has a much higher flow velocity than the inner disperse phase. While passing through the orifice, the prevailing pressure drop and shear stress force the inner phase to break up into uniform droplets. Using a biodegradable poly(lactide-co-glycolide) (PLGA) polymer solution as the disperse phase, monodisperse and user-defined polymer micro- and nanospheres can be generated. Here we present a consecutive parameter study of hydrodynamic flow focusing to study the effect of chemical and physical parameters that effect the dispersity of the droplets generated in the 1-5 μm range. The parameter study shows the applicability and challenges of hydrodynamic flow focusing in the preparation of biodegradable microspheres. Applications for microspheres made with this method can be found in the medical, pharmaceutical and technical fields.

Preparation of biodegradable microspheres containing repaglinide

The objective of the present study is to prepare and evaluate poly(e-caprolactone) microspheres of repaglinide by using the solvent evaporation technique. The microspheres were prepared with different drug-to-carrier ratios: F1 (1:3), F2 (1:4), F3 (1:5), and F4 (1:6). The microspheres were then evaluated for particle size, SEM, FT-IR study, percentage yield, drug entrapment, stability studies, and for in vitro release kinetics. Scanning electron microscopy (SEM) revealed that microspheres were spherical with a nearly smooth surface morphology. The percentage yield and drug entrapment efÞ ciency were high for all the formulations. Fourier Transform-Infrared spectroscopy (FT-IR) showed that there was no chemical interaction between the drug and the polymer. No appreciable difference was observed in the stability study, in the extent of degradation of the product for 60 days in the microspheres that were stored at various temperatures. The in vitro release study showed that replaglinide release from all the formulations was slow and sustained over 12 h. Application of the in vitro drug release data to various kinetic equations indicated zero order release from repaglinide microspheres. Key words: Biodegradable, microspheres, poly(e-caprolactone), repaglinide.

Preparation of biodegradable microspheres by anionic dispersion polymerization with PLA copolymeric dispersion stabilizer

We prepared poly(d,l-lactide) (PLA) microspheres by anionic dispersion polymerization of d,l-lactide. The polymerization was carried out in xylene/heptane (1:2 in v/v) mixture solution at 368 K for 9 h, with poly(dodecyl methacrylate)-co-poly[α-methacryloxyethoxy-poly(l-lactide)] (PDMA-co-P(MA-PLLA)) synthesized in this study, as a dispersion stabilizer. The number-averaged diameter and diameter distribution (coefficient of variation) of obtained PLA microspheres ranged from 180 to 800 nm and 14–40%, respectively, depending on the preparation condition. Furthermore, the time courses of monomer conversion, particle diameter, and particle number were investigated to clarify the formation mechanism of microspheres with PDMA-co-P(MA-PLLA) as a dispersion stabilizer. From this experiment, we found that the aggregation of primary particles occurred in anionic dispersion polymerization, and the particle diameter of obtained PLA microspheres decreased with increasing PDMA-co-P(MA-PLLA) concentration. In conclusion, we clarified that PDMA-co-P(MA-PLLA) effectively contributed to the stability of primary particles.

Research on stability of proteins in biodegradable microspheres

维持蛋白质药物的稳定性是其聚合物微球化过程工艺设计和优化的关键.综述了制备蛋白质可生物降解聚合物微球过程中影响蛋白质稳定性的主要因素,着重介绍了保护蛋白质活性损失的先进策略.选择精确的蛋白质稳定性的分析技术才能得到对结果的真实评价。

Preparation of biodegradable microspheres and matrix devices containing naltrexone.

In this study, the use of biodegradable polymers for microencapsulation of naltrexone using solvent evaporation technique is investigated. The use of naltrexone microspheres for the preparation of matrix devices is also studied. For this purpose, poly(L-lactide) (PLA) microspheres containing naltrexone prepared by solvent evaporation technique were compressed at temperatures above the Tg of the polymer. The effect of different process parameters, such as drug/polymer ratio and stirring rate during preparation of microspheres, on the morphology, size distribution, and in vitro drug release of microspheres was studied. As expected, stirring rate influenced particle size distribution of microspheres and hence drug release profiles. By increasing the stirring speed from 400 to 1200 rpm, the mean diameter of microspheres decreased from 251 microm to 104 microm. The drug release rate from smaller microspheres was faster than from larger microspheres. However, drug release from microspheres with low drug content (20% wt/wt) was not affected by the particle size of microspheres. Increasing the drug content of microspheres from 20% to 50% wt/wt led to significantly faster drug release from microspheres. It was also shown that drug release from matrix devices prepared by compression of naltrexone microspheres is much slower than that of microspheres. No burst release was observed with matrix devices. Applying higher compression force, when compressing microspheres to produce tablets, resulted in lower drug release from matrix devices. The results suggest that by regulating different variables, desired release profiles of naltrexone can be achieved using a PLA microparticulate system or matrix devices.

Fatty acid substituted polyvinyl alcohol as a supporting material for microsphere preparation

Polyvinyl alcohol, substituted with lauric, myristic, palmitic, and stearic acids at different substitution degrees was employed for the preparation of biodegradable microspheres containing progesterone or indomethacin. A solvent extraction/method was followed, starting from an oil-in-water dispersion containing the polymer and drug in the inner phase. Microspheres were obtained with high loading efficiency, whose release properties were dependent on the nature of the acyl substituent and the substitution degree. Kinetics approaching zero-order were obtained for the most hydrophile microspheres such as those based on the least substituted polymers and lowest molecular weight substituents. The hydrophilicity of these systems hindered protein absorption on their surface, suggesting their suitability for parenteral use.

Preparation of Biodegradable Microspheres of Testosterone with Poly(d,l-Lactide-co-Glycolide) and Test of Drug Releasein Vitro

Biodegradable microspheres formulation of testosterone (T) can be used as a new physiological approach for androgen replacement in hypogonadal men. In this study, poly(D,L-lactide-co-glycolide) (PLGA) microspheres containing T were prepared by a solvent-evaporation/solvent-diffusion process and the drug release tests of the microspheres were carried out in vitro. T/PLGA microspheres with good yield, desired size and satisfied drug loading were obtained. A significant testosterone sustained release was shown in the drug release tests in vitro. Since PLGA microspheres preparations are normally sterilized by colbat-60 irradiation, the effects of 25 kGy colbat-60 irradiation on physicochemical properties and in vitro drug release profile of T/PLGA microsphere were investigated. The results showed that the irradiation didn't have any effects on the physicochemical properties of T. Though about one-third decrease in molecular weight of PLGA was caused by the irradiation, no significant changes were observed on the drug release profile in vitro.

Preparation of biodegradable microspheres containing water-soluble drug, β-lactam antibiotic

Poly (l-lactic acid) (PLLA) microspheres loaded with ampicillin sodium (AMP-Na), β-lactam antibiotic, were prepared by a w/o/w multiple emulsion-solvent evaporation method. The amounts of each component in three phases (inner water phase, organic phase, and outer water phase) were carefully examined in the preparation of PLLA microspheres. The stirring rate, another preparation parameter, was also investigated for study on the effect of mechanical stress on the drug loading and morphology of PLLA microspheres. Most of the preparation parameters had a great influence on the drug loading, surface morphology and size distribution of PLLA microspheres. PLLA microspheres with 15.89 w/w% drug loading were subjected to thein vitro release experiment. The release of ampicillin sodium was constant at a rate of 1.68 μg/ml/day per 1 mg of microspheres for 18 days after a 4 days initial burst effect.

Preparation of biodegradable microspheres and microcapsules: 2. Polyactides and related polyesters

Abstract This review presents a general survey of the manufacturing methods of microspheres and microcapsules based on biodegradable polyesters, including polylactides, polyglycolide, polyhydroxybutyrate, polycaprolactone, polycarbonates and related copolymers. Various procedures and modifications of solvent evaporation and solvent extraction techniques employed for these preparations are described. The effects of process parameters (e.g. polymer concentration, stirring speed and mode of solvent removal) on microsphere/microcapsule characteristics (e.g. panicle size, porosity and release pattern) are also outlined.