Effect of Temperature of Dissolution on The Release Kinetics of Phenobarbitone from Poly (Dl-Lactic Acid) Microcapsules: Calculation of Activation Energy.

Abstract

Poly (DL-lactic acid) [DL-PLA] microcapsules containing phenobarbitone (core:polymer, 1:2) were prepared using three different molecular weight polymers, 20,500, 13,300 and 5,200. Buffer pH 9 ware used to study dissolution rate at temperatures of 10°, 15°, 20°, 25°, 30° and 37°C. The release mechanism followed “Higuchi's” square root of time relationship at all these temperatures and allowed calculation of release rate from the straight line portion of release curve. These microcapsules showed an initial burst phase release followed by a lag phase; both of these phases are affected by the temperature of dissolution and polymer molecular weight. The normalized release rate [K_h2/SSA] was found to lower linearly with the lowering of temperature with all three polymers. Arrhenius plot of the normalized release rate allowed calculation of the activation energy (Ea) for the polymers. It was found to lower linearly with the increase in DL-PLA polymer molecular weight.     

涂层工艺对聚碳酸亚乙酯载药涂层性能和体外释放动力学的影响

为了考察不同涂层工艺对冠脉支架涂层的影响,分别采用手动浸涂和自动超声喷涂法在316L不锈钢冠脉支架基体表面制备含雷帕霉素的聚碳酸亚乙酯(PEC)涂层.首先对PEC进行了凝胶渗透色谱(GPC)、差示扫描量热(DSC)以及拉伸实验测试,初步证明其物理化学性质适合作支架可降解涂层材料.然后用扫描电子显微镜( SEM)、原子力显微镜(AFM)、接触角测定仪、球囊扩张法等对涂层表面的形貌、亲水性以及涂层和支架基体的结合力进行分析,并在PBS(pH=7.4)模拟体液中测试上述两种工艺方法制备的药物洗脱支架体外药物释放动力学曲线.结果表明,上述两种方法制备的药物涂层在微观结构、亲水性以及与支架的结合力方面存     

Effects of Microwave on Drug Release Property of Poly(Methyl Vinyl Ether-co-Maleic Acid) Matrix

ABSTRACT

The drug release behavior of beads made of poly(methyl vinyl ether-co-maleic acid) was investigated with respect to the influence of microwave irradiation. The beads were prepared by an extrusion method with sodium diclofenac as a model water-soluble drug. The beads were subjected to microwave irradiation at 80 W for 5 and 20 min, and at 300 W for 1 min 20 s and 5 min 20 s. The profiles of drug dissolution, drug content, drug-polymer interaction, and polymer-polymer interaction were determined by using dissolution testing, drug content assay, differential scanning calorimetry, and Fourier transform infra-red spectroscopy. Keeping the level of supplied irradiation energy identical, treatment of beads by microwave at varying intensities of irradiation did not bring about similar drug release profiles. The extent and rate of drug released from beads were markedly enhanced through treating the samples by microwave at 80 W as a result of loss of polymer-polymer interaction via the (CH₂)_n moiety, but decreased upon treating the beads by microwave at 300 W following polymer-polymer interaction via the O-H, COOH, and COO^? moieties as well as drug-polymer interaction via the N-H, O-H, COO^?, and C-O moieties. The beads treated by microwave at 300 W exhibited a higher level of drug release retardation capacity than those that were treated by microwave at 80 W in spite of polymer-polymer interaction via the (CH₂)_n moiety was similarly reduced in the matrix. The mechanism of drug release of both microwave-treated and untreated beads tended to follow zero order kinetics. The drug release was markedly governed by the state of polymer relaxation of the matrix and was in turn affected by the state of polymer-polymer and/or drug-polymer interaction in beads.     

聚乳酸-聚丁二酸丁二醇酯嵌段共聚体系对聚乳酸熔体流变性能的影响

采用未封端的聚乳酸(PLA1)和聚丁二酸丁二醇酯(PBS)通过大分子链末端直接脱水酯化反应制备聚乳酸-聚丁二酸丁二醇酯嵌段共聚体系(LB),并对比研究LB体系及纯PBS两种改性剂对封端聚乳酸(PLA)熔体流变性能的影响。流变测试结果证明,LB或PBS的添加均使PLA的储能模量有较明显的提高。但当改性剂的含量相同时,LB对PLA熔体流变性能的提高幅度明显高于PBS,这可能是因为在LB共聚体系中除传统的"海岛"结构外还形成了新的PLA1-PBS"核壳"结构。     

Dissolution of Suppositories IV: Effect of Crospovidone on Aspirin Release from Peg Bases

Abstract

Previous reports from this laboratory have described a suppository dissolution test apparatus as wall as the use of crospovidone to increase rate of release of acetaminophen from PEG suppositories. Also in previous reports from this lab, aspirin has been shown to give slow release from PEG bases and it was posited that addition of crospovidone to aspirin suppositories would also increase the rate of release. To test this hypothesis, four PEG blends were used as bases as in the previous studies. Each contained 350 mg of aspirin and 0.5%, 1%, or 5% of crospovidone (Polyplasdone XL, GAF). One thousand milliliters of phosphate buffer of pH 8.0 to approximately rectal pH was used as the dissolution media and maintained at 37.5°. A constant agitation rates of 25, and 50 rpm were used. Aspirin was assayed spectrophotometrically at 265 nm after appropriate dilution. Comparative dissolution profiles of the various agitation rates and with the concentrations of crospovidone were developed. Addition of crospovidone increased the dissolution rate constant and decreased dissolution half-times at the agitation rates. While the disintegration aide increased release, this release was not linear with respect to disintegrating agent concentration.     

磺化聚醚醚酮对苯并噁嗪固化动力学的影响

采用磺化聚醚醚酮(SPEEK)对苯并噁嗪(Ba)进行催化固化。通过非等温差示扫描量热仪研究SPEEK对Ba的催化固化反应影响。进一步采用Kissinger、Ozawa和Crane法对Ba/SPEEK体系的固化动力学参数进行了计算。结果表明,SPEEK可明显降低Ba的固化温度。升温速率为10℃/min,SPEEK用量为0.1%时,Ba的固化起始温度和固化峰值温度分别降低26.1℃和9.7℃。用量增加到0.5%后,催化固化效果趋于平缓。0.3%的SPEEK使Ba固化反应活化能降低12 k J/mol。     

Compression of Microcapsules I: Effect of Excipients and Pressure on Drug Release

Abstract

Microcapsules containing phenylpropanolamine-resin complexes were compressed with various diluents. Compression of microcapsules produced an increase in the release rate. An average reduction of 0.50 hours was observed when Emdex or Fast Flo Lactose were compared to Avicel at various pressures (35 to 281 MPa). Increasing the amount of microcapsules in the formulation reduced the T50% with all three diluents     

Compression of Microcapsules I: Effect of Excipients and Pressure on Drug Release

Microcapsules containing phenylpropanolamine-resin complexes were compressed with various diluents. Compression of microcapsules produced an increase in the release rate. An average reduction of 0.50 hours was observed when Emdex or Fast Flo Lactose were compared to Avicel at various pressures (35 to 281 MPa). Increasing the amount of microcapsules in the formulation reduced the T50% with all three diluents     

水泥石自修复用聚脲甲醛微胶囊的制备及性能

采用原位聚合法制备聚脲甲醛包覆水性环氧树脂微胶囊,测定其产率及含芯量,表征了表面形貌及化学结构,并考察了微胶囊水泥石修复性能。结果表明:芯壁比为2.4∶1时微胶囊最佳,含芯量达76.1%,粒径约为200μm;微胶囊掺量为1%时,水泥石同时具有良好的压缩强度和修复性能,极限预破坏修复率为87%;预破坏程度为60%时,修复率最高;微胶囊粗糙蓬松的外壁与水泥石基体有良好的胶接性,内壁厚约0.5μm,易在水泥石基材中发生应力撕裂而发挥修复作用。     

Dissolution of Suppositories III: Effect of Insoluble Polyvinylpyrrolidone on Acetaminophen Release

Previously reported studies from this laboratory have demonstrated the usefulness of a new apparatus for suppository dissolution study. Acetaminophen suppositories gave slow release and it was posited that addition of a disintegrating agent commonly used in tablet manufacture would increase this release rate. To test the hypothesis, four PEG blends were used as bases as in the previous studies. Each contained 320 mg acetaminophen and 1%, 5%, or 10% of insoluble polyvinylpyrrolidone (Polyplasdone XL^R). One thousand milliliters of phosphate buffer, pH 8.0 to approximate rectal pH was employed as the dissolution media and maintained at 37.5°. A constant agitation rate of 2 5 and 50 rpm was used. Acetaminophen was assayed spectrophotometrically at 243 nm. Comparative dissolution profiles at the various agitation rates and with the concentrations of polyvinylpyrrolidone were developed. Addition of insoluble polyvinylpyrrolidone increased the dissolution rate constant and dissolution half-times at the two agitation rates. While the disintegration aid increased release, this release was not linear with respect to disintegrating agent concentration.

Release of acetaminophen from suppositories and the bioavailability of acetaminophen Erom suppository bases have not received much study. Feldman reported that the rate of bioavailability of suppositories was extremely variable and might not produce a clinically noted response (1). Maron and Ickes, however, reported that acetaminophen suppositories were clinically as effective an antipyretic as were tablets (2).

Pagay, et al. studied the influence of the vehicle on the bioavailability of acetaminophen suppositories using a modified beaker method with a media of pH 7.0 and an agitation of 25 rpm (3). These researchers correlated the dielectric constant of the base to acetaminophen bioavailability. Commercial suppositories were not discussed.

A recent report by Palmieri (4) discussed release of acetaminophen from laboratory prepared PEG bases and commercially available suppositories. Dissolution half-times for laboratory prepared suppositories at 50 rpm ranged from 8 minutes for Base A to 22 minutes for Base D. The commercially available acetaminophen suppositories had a dissolution half-time of 90 minutes at 50 rpm. Because of these apparently slow release rates, it was posited that addition of a disintegrating agent would increase the release of acetaminophen from the polyethylene glycol base sup-positores. Polyplasdone XLR, (5) a crosslinked insoluble homopolymer of n-vinyl-2-pyrrolidone was used in an attempt to increase the release rate.     

Dissolution of Suppositories III: Effect of Insoluble Polyvinylpyrrolidone on Acetaminophen Release

Abstract

Previously reported studies from this laboratory have demonstrated the usefulness of a new apparatus for suppository dissolution study. Acetaminophen suppositories gave slow release and it was posited that addition of a disintegrating agent commonly used in tablet manufacture would increase this release rate. To test the hypothesis, four PEG blends were used as bases as in the previous studies. Each contained 320 mg acetaminophen and 1%, 5%, or 10% of insoluble polyvinylpyrrolidone (Polyplasdone XL^R). One thousand milliliters of phosphate buffer, pH 8.0 to approximate rectal pH was employed as the dissolution media and maintained at 37.5°. A constant agitation rate of 2 5 and 50 rpm was used. Acetaminophen was assayed spectrophotometrically at 243 nm. Comparative dissolution profiles at the various agitation rates and with the concentrations of polyvinylpyrrolidone were developed. Addition of insoluble polyvinylpyrrolidone increased the dissolution rate constant and dissolution half-times at the two agitation rates. While the disintegration aid increased release, this release was not linear with respect to disintegrating agent concentration.

Release of acetaminophen from suppositories and the bioavailability of acetaminophen Erom suppository bases have not received much study. Feldman reported that the rate of bioavailability of suppositories was extremely variable and might not produce a clinically noted response (1). Maron and Ickes, however, reported that acetaminophen suppositories were clinically as effective an antipyretic as were tablets (2).

Pagay, et al. studied the influence of the vehicle on the bioavailability of acetaminophen suppositories using a modified beaker method with a media of pH 7.0 and an agitation of 25 rpm (3). These researchers correlated the dielectric constant of the base to acetaminophen bioavailability. Commercial suppositories were not discussed.

A recent report by Palmieri (4) discussed release of acetaminophen from laboratory prepared PEG bases and commercially available suppositories. Dissolution half-times for laboratory prepared suppositories at 50 rpm ranged from 8 minutes for Base A to 22 minutes for Base D. The commercially available acetaminophen suppositories had a dissolution half-time of 90 minutes at 50 rpm. Because of these apparently slow release rates, it was posited that addition of a disintegrating agent would increase the release of acetaminophen from the polyethylene glycol base sup-positores. Polyplasdone XLR, (5) a crosslinked insoluble homopolymer of n-vinyl-2-pyrrolidone was used in an attempt to increase the release rate.     

一种酰胺类成核剂对聚乳酸结晶行为的影响

通过自主设计合成一种含酰胺结构的新型成核剂——1,6-二苯基己烷基脲(NA6),并利用差示扫描量热仪(DSC)和偏光显微镜(POM)研究了NA6成核剂(1~8wt%)对聚乳酸(PLLA)结晶行为的影响。结果表明,随着NA6成核剂含量的增加,PLLA的结晶温度由93.8℃提高到118.6℃,结晶度由12.0%提高到65.5%;130℃时的等温结晶速率提高到0.56min-1,是纯PLLA的14.5倍。此外,NA6成核剂可显著减小PLLA的球晶尺寸,且随着成核剂含量的提高成核效果愈加明显。     

氢键作用对制备线性聚丙烯酸纳米粒子的影响

无稳定剂和交联剂的情况下,在乙腈中利用蒸馏沉淀聚合的方法制备无交联的聚丙烯酸（polyAA）纳米粒子.不同的反应条件下,考察引发剂偶氮二异丁腈（AIBN）和单体丙烯酸（AA）浓度的影响.结果表明最佳的聚合反应条件为AIBN相对于单体质量2%,AA相对于反应介质体积2.5%,在这个条件下线性polyAA纳米粒子的粒径约为254 nm.此外,以纯化后的polyAA纳米粒子作为种子,在引发剂和AA单体存在的条件下,通过种子蒸馏沉淀聚合可得到大粒径的纳米粒子.由于AA单体中羧基间的氢键作用,AA单体被认为是自身交联剂,氢键导致了AA双胞体的形成.在聚合体系中加入三乙胺,AA单体间的氢键被破坏.结果表明：几乎没有线性polyAA纳米粒子合成,当三乙胺的量超过AA单体时,只能得到凝胶,而得不到纳米粒子.     

Enhanced Release of Drugs from Silicone Elastomers (I) Release Kinetics of Pineal and Steroidal Hormones

Abstract

The release of melatonin, estradiol, and flourogestone acetate from subdermal implants was enhanced when implants were fabricated from silicone elastomers containing co-solvents. This enhancement followed a Q vs. t relationship. As glycerol concentration increased, the increments in release rate were greater for hydrophilic drugs than for hydrophobic drugs. When drug loading in the implants was held constant, release rates were found to be a function of glycerol concentrations in the device. A synergistic enhancement of release rate was observed when both glycerol and sodium chloride were added to the silicone matrix. The fact that co-solvents enhance the rate of drug release from silicone elastomers indicates that a reduction in the activation energy required for drug release may occur.     

Enhanced Release of Drugs from Silicone Elastomers (I) Release Kinetics of Pineal and Steroidal Hormones

The release of melatonin, estradiol, and flourogestone acetate from subdermal implants was enhanced when implants were fabricated from silicone elastomers containing co-solvents. This enhancement followed a Q vs. t relationship. As glycerol concentration increased, the increments in release rate were greater for hydrophilic drugs than for hydrophobic drugs. When drug loading in the implants was held constant, release rates were found to be a function of glycerol concentrations in the device. A synergistic enhancement of release rate was observed when both glycerol and sodium chloride were added to the silicone matrix. The fact that co-solvents enhance the rate of drug release from silicone elastomers indicates that a reduction in the activation energy required for drug release may occur.     

Dissolution Rate of Griseofulvin from Solid Dispersions with Poly(Vinylmethylether/Maleic Anhydride)

Abstract

A solid dispersion technique with poly(vinylmethylether/ maleic anhydride) (PVM/MA) and its half esters has been used to enhance griseofulvin dissolution.

A marked increase of the dissolution rate and solubility of griseofulvin contained in these solid dispersions was observed compared with that of drug alone and that of physical mixture with the carrier.

Differences in dissolution rates resulted from the molecular weight and the chemical structure of the carrier.

X-Ray powder diffractometry, differential scanning calorimetry (DSC) and wettability tests were employed to investigate the nature of the studied forms.     

可降解材料聚碳酸亚丙酯和聚乳酸的溶度参数与相容性

采用基团贡献法求出了聚碳酸亚丙酯(PPC)和聚乳酸(PLA)的一维溶度参数和Hansen三维溶度参数理论值,并通过溶解试验获得了PPC和PLA的三维溶度参数值,结合Teas图分析了聚合物与溶剂之间的溶度参数距离(Ri)和Flory-Huggins相互作用参数(χAB),预测和分析了PPC和PLA的相容性。结果表明,PPC和PLA的一维溶度参数理论值分别为20.37(J/cm³)1/2、19.97 (J/cm³)1/2; PPC的Hansen三维溶度参数(δd、δp、δh)和总溶度参数理论值(δ)分别为14.68 (J/cm³)1/2、7.37 (J/cm³)1/2、10.79 (J/cm³)1/2和19.65 (J/cm³)1/2,PLA的分别为15. 45 (J/cm³)1/2、8.51 (J/cm³)1/2、11.02 (J/cm³)1/2和20.80 (J/cm³)1/2;试验法得出PPC的δd、δp、δh、δ分别为16.94 (J/cm³)1/2、7.05 (J/cm³)1/2、6.75 (J/cm³)1/2、19.56 (J/cm³)1/2,PLA的则分别为16.83 (J/cm³)1/2、6.40 (J/cm³)1/2、6.70 (J/cm³)1/2、19.21 (J/cm³)1/2,且在Teas图中,所有良溶剂位于一定的溶解区域内,不良溶剂位于区域外,聚合物与良溶剂的Ri小于与不良溶剂的Ri,聚合物与良溶剂的χAB小于0.5,与不良溶剂的χAB大于0.5,表明试验结果可信;通过理论计算和试验法求出PPC和PLA都具有相近的溶度参数值,且溶度参数差值的绝对值(Δ)位于0.077～1.300 (J/cm³)1/2之间,表明两者之间为部分相容。     

D-山梨醇对聚丙烯酸-水基氧化铝悬浮液流变性能的影响

研究了D-山梨醇(D-sorbitol)对聚丙烯酸(poly(acrylic acid))(PAA)稳定的水基氧化铝(Al₂O₃)悬浮液流变性能的影响. 实验发现: 在pH为9.0时, 对于固含量为30vol% ~ 40vol%的Al₂O₃悬浮液, 少量D-山梨醇的加入皆能明显提高其分散稳定性. 当D-山梨醇的添加量占分散剂总量(0.5wt%)的20%时, 悬浮液粘度最低. 且添加二元分散剂PAA/D-山梨醇的悬浮液具有更好的抗电解质性能. 分别对单一PAA分散的Al₂O₃及二元分散剂分散的Al₂O₃进行了红外光谱表征. 结合流变与红外实验结果, 分析了山梨醇的作用机理: 部分山梨醇吸附在Al₂O₃颗粒表面, 部分山梨醇与PAA以氢键形式结合, 增大了颗粒间的空间位阻, 提高了悬浮液的流变性能.     

磺化聚芳醚酮砜的热降解动力学

通过热重分析仪(TGA)对作为质子交换膜材料使用的磺化聚芳醚酮砜(SPAEKS)进行了热性能研究.采用不同的升温速率,分别用Kissinger方法和Flynn-Wall-Ozawa方法研究了不同磺化度的SPAEKS在氮气氛围下磺酸基团完全脱落前的热降解动力学.研究表明,通过Kissinger方法计算得到SPAEKS的活...