Drug-Delivery by Ion-Exchange: Part IIII: Interaction of Ester Pro-Drugs of Propranolol with Cationic Exchange Resins

Abstract

The interaction of a series of O-n-acyl propranolol prodrugs with strong cation exchange resins is reported and various variables which control loading and release profiles have been investigated. pH has little practical effect on the loading efficiency under the conditions used but standardisation of experimental details for the measurement of in vitro liberation profiles must be undertaken. In particular, stirring speeds of 200-300 rpm were necessary to ensure the independence of release profile and agitation. Additionally, the dissolution medium may not provide sink conditions throughout the full dissolution process if pH variation does not take into account solubility differences between analogues. Ionic strength also influences release rates and attempts to examine the effects of pH must also control this variable. The proportion of cross-linking agent in the resin plays an important role. Increasing the cross-linking delays considerably the release of drug from the matrix and is a useful parameter in optimising controlled delivery. The loading efficiency of the resin is reduced, however, as the cations are excluded from parts of the resin due to a reduction in pore diameter. In contrast, the particle size of the resin has little influence upon loading efficiencies but larger particles significantly delay the release of drug. The effect of 0-n-acyl chain-length on the loading and release profiles was determined by molecular size. As groups increased in size the loading was inhibited and release rates were reduced. Again, this enables some control of release profiles but the approach is most suitable for drugs which are active at low doses which allow full use of these variations without the necessity for large amounts of resin in the delivery system.     

肥料养分控释的技术、机理和质量评价

本文从肥料养分释放与作物吸收的"供—求"平衡关系出发,阐述了养分控释的重要意义;列举了养分控释的主要技术途径及其作用机理,并从控释材料来源、设备选型、控释效果等方面对各种技术途径进行了评述;在控释肥质量评价方面,说明了引入土壤因子的重要性,认为把"肥—土"作为一个整体来考虑,有利于更客观、更合理地评价控释肥的质量。     

不同土壤肥力条件下水稻控释氮肥效应及其氮素利用的研究

田间试验在湖南的衡山县和长沙县进行,探讨了不同肥力水平水稻土上水稻控释氮肥对早、晚稻的增产效果和肥料氮利用率.结果表明,在肥力水平较低的水稻土上施用水稻控释氮肥对水稻的增产效果极为显著,应当增加施用量;在肥力水平较高的水稻土上,水稻吸收土壤氮较多,肥料氮的吸收量与增产作用自然减少,应适当减少施用量.不同肥力水平的土壤上水稻控释氮肥较等氮量尿素增产4.4%～16.4%.较无氮区增产13.8%～74.5%.水稻控释氮肥在不同肥力水平土壤中早、晚稻的利用率为69.7%～86.9%,平均比等N量尿素高37.6%,且水稻控释氮素利用率的高低与土壤肥力水平有关.水稻控释氮肥作一次性全量基肥施用,氮素生产效率明显高于尿素,是增产的主要原因.     

淀粉/聚乙烯醇全降解缓释塑料薄膜的制备与性能研究

聚乙烯醇(PVA)溶解后与淀粉(St)共混,同时加入增塑剂丙三醇、交联剂甲醛,反应结束后将包膜液流延成膜。考察了m(St)∶m(PVA)、反应温度、丙三醇用量、甲醛加入方式、甲醛用量、反应时间对薄膜性能的影响,并表征了薄膜的结构。结果表明:当m((St)∶m(PVA)=7∶3、反应温度为90℃、w(丙三醇)=3%(占St、PVA、纯水质量之和的质量分数)、甲醛一次性加入、w(甲醛)=2%、反应时间为1 h时,制得的塑料薄膜拉伸强度、断裂伸长率较大,吸水率和透NH4+率均较低,共混体系的相容性好。     

Molybdate doping of networks in epoxy–silica hybrids: Domain structuring and corrosion inhibition

Epoxy–silica hybrids were prepared from a silane-functionalized resin mixture of two diglycidyl ether bis-phenol A oligomers with different molecular weights, using molybdate anions as dopants for the siloxane domains.     

In vivo evaluation of two novel controlled-release nitrendipine formulations

The objective of this work is to assess two novel controlled-release nitrendipine formulations, i.e., sustained-release nitrendipine microspheres having solid dispersion structure and a novel pH-dependent gradient-release delivery system for nitrendipine in healthy male volunteers, which were prepared by current authors. Domestic commercial nitrendipine tablets and Baypress™ nitrendipine tablets were employed as reference formulations. In a randomized, single-dose, fasting-state, crossover study design with a 1-week washout period, each subject received a 40-mg nitrendipine formulation. Plasma samples were collected over a 25-hour period after oral administration and were analyzed by a validated method using high performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined using a noncompartmental analysis. The results provided evidence that the time to maximum plasma concentration of two novel controlled-release nitrendipine formulations were statistically significant prolonged in comparison with that of Baypress™ nitrendipine tablets. The relative bioavailabilities of test formulations were intensively improved compared with the domestic nitrendipine tablets, while the ratio is in a range of 80-120% in comparison with Baypress™ nitrendipine tablets. It is concluded that the two types of controlled-release systems are feasible for improving the dissolution rate of nitrendipine and obtaining a long-acting in vivo as well.     

Eudragit NE40–Drug Mixed Coating System for Controlling Drug Release of Core Pellets

This study was aimed at developing a controlled-release coating system around core pellets with aqueous dispersion, along with some water channeling agents. Core pellets of diltiazem were prepared using the extrusion-spheronization technique and subsequently coated with aqueous dispersion of Eudragit NE40 alone, or drug–polymer mixtures using bottom-spray fluidized bed coater. The lag time in drug release profiles increased as the coating levels of Eudragit NE40 were increased, whereas no lag time was observed in core pellets coated with drug–polymer mixtures. Mixed coating at the 7% level exhibited comparatively better release profiles and provided desirable release rates during the 12-hour testing interval. Diltiazem HCl release from mixed coating was fairly independent of pH and drug loading. Curing of coated pellets was found to be an essential step for stable drug release profiles. The selection of core size range had remarkable effect on drug release rate and was considerably reduced by using greater core size.     

Biodegradable Polymer-Based Controlled Release Systems: The Physicochemical Aspects. Part I. Systems and Mechanisms

Abstract

Typical systems biodegradable polymer-drugs for the treatment of different diseases are considered and also the dosage forms used therein. Biodegradable polymers are classified as to degradation mechanism, hydrolysis mechanism and solubilization mechanism. Influence of the distribution type of drug in biodegradable polymer is described in relation to release rate.     

Formulation and Pharmacokinetic Studies of Acyclovir Controlled-Release Capsules

Acyclovir controlled-release capsules (CRCs) were prepared by a three-step process: [1] melt granulation of acyclovir; [2] coating of granules with ethylcellulose; [3] incorporation of coated granules into hard gelatin capsules. In vitro release experiments showed that the main factors affecting the release rate were the mean particle size of the acyclovir raw material and the amount of coating material applied. Release of acyclovir from the capsules was in accordance with the Higuchi equation. Pharmacokinetic studies in dogs after oral administration of acyclovir controlled-release capsules showed that the formulation was successful in providing slow release of acyclovir and was superior to a commercially available controlled-release formulation.     

Nitrous oxide and nitric oxide fluxes from an upland field in Japan: effect of urea type, placement, and crop residues

Fertilizer type and application mode may influence nitrous oxide(N₂O) and nitric oxide (NO) emissions as well as crop yield. Using astatic chamber method, fluxes of both gases from a Chinese cabbage field inJapan were measured in situ following the application of easily decomposableurea by broadcasting (U-BC) and banding (U-B) and coated urea by banding(CU-B),respectively, at an application rate of 250 kg Nha^–1. The measurements were made throughout the growingseason and continued 3 more months after harvest to determine the effect ofcropresidues on the emissions. Large N₂O fluxes from U-BC occurredwithinabout 2 weeks after the application of the N fertilizer, while that from bothU-B and CU-B was prolonged by about 2 weeks, and significant emissions lasted alonger time but with a smaller emission size. Substantial N₂O fluxesderived from crop residues were observed in the late growing season (especiallyfollowing rainfall) as well as after harvest, at all treatments including thecontrol plots (CK). Large NO fluxes occurred only at U-BC within the first 2weeks through the measurements. Total emissions were estimated to be 38.1,78.3,77.8, and 100.4 mg N₂O-N m^–2 and 0.7,194.9, 8.5, and 11.4 mg NO-N m^–2 at CK, U-BC,U-B,and CU-B, respectively. Statistical analyses indicate that neither the bandmodenor the coated urea was able to significantly reduce the total N₂Oemission through the season, but the band mode substantially reduced the NOemission. However, the application of urea by the band mode presented a 22.8%increase in crop yield as compared with urea applied by broadcasting.Therefore,by improving fertilizer use efficiency to decrease the amount of N needed tobetter meet the crop growing demand, the band mode may be a good agriculturalpractice to also reduce N₂O emission. In addition, the experimentdemonstrated that crop residue is a large source of N₂O emission.