Characterization of recrystallized itraconazole prepared by cooling and anti-solvent crystallization

The objective of the present study was to alter the crystal habit of itraconazole (ITZ) by cooling and anti-solvent crystallization and characterize its properties. ITZ was recrystallized in different solvents and the effects of each solvent on morphology of crystals, dissolution behavior and solid state of recrystallized drug particles were investigated. The results revealed that ITZ crystals recrystallized by cooling and anti-solvent crystallization showed the different crystal habits from the untreated ITZ. Using cooling crystallization tended to provide needle-shaped crystals while the crystals obtained from anti-solvent crystallization showed more flaky, plate shape. This indicated the importance of preparation method on nucleation and crystal growth. No change in drug polymorphism was observed, according to determination of thermal property and crystalline state by differential scanning calorimetry and powder X-ray diffractometry, respectively. The recrystallized ITZ showed higher drug dissolution than untreated ITZ and the highest drug dissolution was observed from the samples recrystallized in the presence of PEG 200, which provided the small plate-shaped crystals with tremendously increased in surface area. However, the increasing of drug dissolution is relatively small, therefore, further development may be required.     

海洋产物的剂型研究进展

基金项目:国家自然科学基金(82374038);连云港市中医药科技发展计划项目     

氟马西尼的药理、药效和剂型应用进展

氟马西尼作为苯二氮GFDA1（BDZ）受体拮抗剂,能特异性结合中枢BDZ受体,减少γ-氨基丁酸（GABA）的释放,从而拮抗BDZ类、非BDZ类药物引起的抗焦虑、镇静催眠、麻醉等作用。根据其作用靶点和方式,就目前氟马西尼在临床、科研上的应用和剂型进展做一综述。     

Pharmacokinetic evaluation of novel sustained-release dosage forms of valproic acid in humans

Five new sustained-release dosage forms of valproic acid (VPA) were developed. The new sustained-release formulations were administered to six healthy subjects for comparison with a standard tablet and an i.v. preparation of the drug. Three of the formulations exhibited a more prolonged and uniform absorption rate and yielded more sustained serum levels after ingestion. These three formulations maintained serum therapeutic levels of VPA for 24 h after a single oral administration of 1 g, and were bioequivalent to a marketed standard tablet of VPA. The absorption profile of the various oral formulations was analysed pharmacokinetically, using the Loo-Riegelman procedure.     

Relative bioavailability of three commercial quinidine dosage forms

Bioavailabilities of three quinidine formulations were compared. Two tablets of each dosage form were administered to 12 healthy volunteers according to a repeated Latin square design; plasma levels of unchanged and total drug were determined. Quinidine was absorbed significantly more rapidly from one of the formulations than the other two; the bioavailability of this formulation, calculated from intact drug data, normalized for subject differences, was also significantly greater than that of the other two, 68 and 76 per cent respectively. Individual comparisons of area under the curve (AUC) indicated that estimated relative bioavailability depends on the specificity of the assay, the adjustment of the AUC for the area beyond the last measurable plasma concentration and the normalization of the AUC. The data suggest there is a correlation between dissolution rate and peak plasma concentration.     

Simultaneous determination of metronidazole and miconazole in pharmaceutical dosage forms by RP-HPLC

A reversed-phase high performance liquid chromatography (RP-HPLC) method with UV detection is described for the simultaneous determination of metronidazole and miconazole in pharmaceutical dosage forms. Chromatography was carried out on a C18 reversed-phase column, using a mixture of methanol-water (40+60, v/v) as a mobile phase, at a flow rate of 1.0 ml min⁻¹. Sulfamethoxazole was used as an internal standard and detection was performed using a diode array detector at 254 nm. The method produced linear responses in the concentration ranges 10-70 and 1-20 μg ml⁻¹ with detection limits 0.33 and 0.27 μg ml⁻¹ for metronidazole and micanozole, respectively. This procedure was found to be convenient and reproducible for analysis of these drugs in ovule dosage forms.     

Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion--Part I

Solid dispersions containing different ratios of itraconazole and hydroxypropylmethylcellulose (HPMC) were prepared by solvent casting. Based on dose, differential scanning calorimetry and dissolution results, a drug/polymer ratio of 40/60 w/w was selected in order to prepare dispersions by melt extrusion. The melt extrusion process was characterized using a design of experiments (DOE) approach. All parameter settings resulted in the formation of an amorphous solid dispersion whereby HPMC 2910 5 mPas prevents re-crystallization of the drug during cooling. Dissolution measurements demonstrated that a significantly increased dissolution rate was obtained with the amorphous solid dispersion compared to the physical mixture. The outcome of DOE further indicated that melt extrusion is very robust with regard to the itraconazole/HPMC melt extrudate characteristics. Stability studies demonstrated that the itraconazole/HPMC 40/60 w/w milled melt extrudate formulation is chemically and physically stable for periods in excess of 6 months as indicated by the absence of degradation products or re-crystallization of the drug.     

口服固体制剂产品生产过程中防止交叉污染及混淆的探讨

本文通过对厂房设施、设备、管理制度、人员培训等方面进行研究探讨,以防止口服固体制剂产品生产过程中的交叉污染以及混淆。     

芍药苷保肝药理作用及新剂型的研究进展

芍药苷是一种单萜糖苷类化合物,其保肝药理活性显著。但芍药苷的脂溶性差导致生物利用度低,起效较慢,限制了其广泛应用,研究和开发芍药苷新剂型以提高生物利用度和药效是当前研究的热点。基于此,本文综合国内外相关文献,对芍药苷保肝药理作用和新剂型的研究进行全面的整理综述,以期为芍药苷的应用和新剂型研发提供理论依据和思路参考。     

Pharmacokinetic analysis of sustained-release dosage forms of theophylline in humans: comparison of single and multiple dose studies

A pharmacokinetic analysis of two sustained-release dosage forms of theophylline (Theo-Dur and Theotrim) was carried out following single and multiple dose administrations of the two formulations in five healthy subjects. Despite the prolonged absorption after administration of the two sustained-release formulations, theoretical predictions of theophylline steady-state levels following multiple dosages based upon data obtained from the single dose study, correlated with the data of the multiple dose study. This study shows that the recommended dose and dosage regimen of new sustained-release formulations of theophylline can be based upon single dose studies. In the population studied, repetitive doses of 450 mg b.i.d. of Theo-Dur and Theotrim maintain steady-state concentrations of theophylline within the drug's therapeutic window.     

如意金黄散对长春瑞滨所致静脉炎的防治作用及其处方优化和剂型选择

目的:探索对如意金黄散进行减方组合后,不同组方对长春瑞滨(用VIN表示)所致静脉炎的防治作用,同时考察其不同剂型的疗效.方法:用均匀设计法结合中药君臣佐使原理对如意金黄散进行拆方组合,以小鼠尾静脉注射VIN造模,以小鼠尾巴肿胀度为疗效指标,观察和比较各组静脉炎的发生、发展及转归情况.结果:大黄、姜黄、生天南星为主的糊剂(D组)、自制如意金黄散全方的糊剂(G组)、大黄、黄柏、厚朴为主的糊剂(F组)及其凝胶剂(F3组)、市售如意金黄散成方的糊剂(Ⅰ组)均显示有效,综合评价认为凝胶剂(F3组)最佳.结论:如意金黄散对VIN所致静脉炎有较明显的防治作用,不同处方及剂型效果有差异.有目的地简化处方可以改善疗效,并有利于针对临床需要进行剂型选择.     

乳癖消现代制剂及其质量控制方法的研究进展

目的 对目前国内销售的乳癖消现代剂型,质量控制方法进行探讨.方法 查阅文献,分类整理,归纳总结.结果 乳癖消现代制剂多为片剂、胶囊剂、贴膏剂等,质量控制方法研究多采用高效液相色谱法,薄层扫描法和气相色谱法.结论 乳癖消现代制剂的研制需以质量稳定、安全、有效为原则,采用现代分析方法,不断完善制剂质量控制的研究.     

Attitude and perception of patients and health care practitioners toward oral sustained release dosage forms in Palestine

Aim

To evaluate the knowledge of health professionals in Palestine regarding the advantages of sustained release dosage forms (SRDFs) over conventional therapy.

Methods

Data were gathered from a questionnaire that was handed out to community pharmacists, physicians and patients. Pharmaceutical industry decision makers were enrolled in this study. Data were analyzed using the SPSS.

Results

Pharmacists (92.9%) and 89.2% of physicians thought that SRDFs improve patient compliance. 81.5% of pharmacists and 77% of physicians were in agreement regarding the capacity of SRDFs to maintain therapeutic activity during night. In this study, 81.5% of pharmacists and 81% of physicians believed that SRDFs provide further advantage with psychiatric patients who forget to take their medications. Pharmacists (63.1%) and only 63.5% of physicians believed that SRDFs yield a time saving for nurses who use SRDFs in hospital. Only 45.3% of physicians and 43.4% of pharmacists thought that SRDFs result in cost saving due to better disease management. Pharmacists (95.2%) and 95.9% of physicians agreed that SRDFs could be the right choice for faith patient’s who must take their medication during the month of Ramadan. Pharmacists (66.7%) and 50.7% of physicians recognize that SRDFs may be unsafe if they are improperly formulated. Bad swallowing was also recognized as inconveniences of SRDFs by 67.9% of pharmacists and 57.3% of physicians. Given the above advantages, 75% of patients showed economical problems regarding the cost of the single course therapy of SRDFs and 100% of interviewed patients were enthusiastic about the advantage of SRDFs during Ramadan.

Conclusion

The advantages of SRDFs are not completely understood by Palestinian health professionals. Pharmaceutical industries should pay more attention to the development and advertising of SRDFs due to the valuable advantages of these dosage forms.     

Floating dosage forms to prolong gastro-retention--the characterisation of calcium alginate beads

Floating calcium alginate beads, designed to improve drug bioavailability from oral preparations compared with that from many commercially available and modified release products, have been investigated as a possible gastro-retentive dosage form. A model drug, riboflavin, was also incorporated into the formula.

The aims of the current work were (a) to obtain information regarding the structure, floating ability and changes that occurred when the dosage form was placed in aqueous media, (b) to investigate riboflavin release from the calcium alginate beads in physiologically relevant media prior to in vivo investigations.

Physical properties of the calcium alginate beads were investigated. Using SEM and ESEM, externally the calcium alginate beads were spherical in shape, and internally, air filled cavities were present thereby enabling floatation of the beads. The calcium alginate beads remained buoyant for times in excess of 13 h, and the density of the calcium alginate beads was <1.000 g cm⁻³. Riboflavin release from the calcium alginate beads showed that riboflavin release was slow in acidic media, whilst in more alkali media, riboflavin release was more rapid.

The characterisation studies showed that the calcium alginate beads could be considered as a potential gastro-retentive dosage form.     

阿联酋与我国药品品种和剂型的比较分析

目的 了解阿联酋药品市场供应情况,为我国药品进入阿联酋提供参考。方法 收集并整理阿联酋药品市场现有药品品种和剂型的相关数据,将其与我国供应的药品品种及剂型进行对比分析。结果 截至2021年12月31日,阿联酋现有药品品规数5 395个,品种数1 637个;根据《新编药物治疗学》（第18版）统计结果,我国药品品种数有1 558个。两国药品品种重合数为604个,两国药品品种差异主要集中在消化道及代谢用药、全身用抗感染药、神经系统用药以及抗寄生虫药、杀虫药和驱虫药等方面。阿联酋现有药品剂型194个,口服给药、注射给药、皮肤给药剂型位列前三位,呼吸系统的药械组合数量远多于我国。结论 中阿两国药品品种和剂型既有共性,也存在差异性,提示我国药品品种在进入阿联酋前,还需对品种进行细化分析;同时我国也可借鉴阿联酋经验,加强新型药械组合的研究力度,以进一步丰富国内药品市场。     

Determination of meprobamate in pharmaceutical dosage forms also containing carbromal by liquid chromatography and indirect photometric detection

In a pharmaceutical form also containing carbromal, meprobamate could not be quantified selectively by classical methods described in pharmacopoeias due to a significant interference from carbromal. Consequently, reversed-phase HPLC methods have been developed to separate the two active ingredients using indirect photometric detection to visualize and determine meprobamate which has very poor chromophoric properties. Different parameters influencing the sensitivity of the indirect response, such as the nature of the highly absorbing compound added to the mobile phase (the marker) as well as the methanol content and the pH of this phase, have been studied. Two chromatographic systems containing benzoic acid or cinnamic acid as the marker, have been optimized and validated. Good linearity and reproducibility have been obtained with both systems but the cinnamic acid method has the advantage that meprobamate and carbromal can be determined simultaneously at 273 nm.     

Characterization of nifedipine microparticles prepared by hot air coating technique

In the present work, the Hot Air Coating (HAC) technique was used to prepare microparticulate systems containing nifedipine. Binary mixtures constituting of nifedipine and cetearyl alcohol (CA) in different proportions (30:70, 50:50, 70:30) were studied: they were homogenized by mixing or milling before spray treatment and successively subjected to a coating procedure with the HAC apparatus fed with air at 120 degrees C under a pressure of 4.5 atm. Morphology, entrapment efficiency, drug stability, thermal behaviour and the drug dissolution profile of HAC-treated and non-treated materials were examined and compared. The HAC products show the possession of physical and physico-chemical properties and dissolution behaviour different from those of the initial physical mixtures. The operative conditions employed in the spray process allow the obtaining of microparticles containing relevant percentages of the drug (at least up to 50%). Moreover, the experimental results give evidence that the milling pre-treatment of mixtures, unlike mixing, has significant effects on the properties of the lipid-coated microparticles.