特非那定片溶出度测定

目的评价市场上6个批号的特非那定片的质量。方法采用桨法作为溶出度测定法，HPLC作为特非那定浓度测定方法，再通过weibull's方程获得溶出度参数。结果仅有2个批号的特非那定片达到卫生部部颁标准。结论我们应该关注市场上特非那定片的质量。     

HPLC determination of olanzapine and carbamazepine in their nicotinamide cocrystals and investigation of the dissolution profiles of cocrystal tablet formulations

Abstract

Cocrystals have recently gained importance in the pharmaceutical industry. In this study, olanzapine and carbamazepine cocrystals were synthesized by using nicotinamide as cocrystal forming agent to achieve improvements in the physicochemical characteristics of the active ingredients. An HPLC method was developed to determine the amount, thus, the stoichiometric ratios of olanzapine and carbamazepine in the synthesized cocrystals. Olanzapine:nicotinamide and olanzapine tablet formulations were prepared and the developed HPLC method was applied successfully in order to compare the dissolution profiles of these formulations. An ACE 5 CN, 25?cm?×?4.6?mm, 5?µm column was used and a gradient elution program was performed for simultaneous determination of olanzapine, carbamazepine and nicotinamide. Phosphate buffer (pH 5.0, 25?mM) and methanol was used in a ratio from 80:20 to 70:30 while the flow rate was 1?mL?min^?1 for the elution of the compounds within 12?min. In conclusion, two different aims were achieved, the first one was to indicate the stoichiometric ratios of the active ingredients olanzapine and carbamazepine with nicotinamide in their cocrystals, and the second one was the comparison of the dissolution profiles of the olanzapine and olanzapine:nicotinamide cocrystal formulations. It was found that the cocrystal formulation with nicotinamide improved the dissolution profile of olanzapine.     

Ketoconazole ion-exchange fiber complex: a novel method to reduce the individual difference of bioavailability in oral administration caused by gastric anacidity

Water insoluble faintly alkaline drugs often have potential absorption problem in gastrointestinal tract in oral administration for patients with gastric anacidity. The purpose of the present study is to develop a novel method to improve the absorption of the water insoluble faintly alkaline drug in peroral administration. This method is based on ion exchange of ion-exchange fibers. Water-insoluble faintly alkaline drug ketoconazole was used as a model drug. Ketoconazole and the active groups of the ion-exchange fibers combined into ion pairs based on the acid-base reaction. This drug carrier did not release drugs in deionized water, but in water solution containing other ions it would release the drugs into the solution by ion exchange. Confirmed by the X-ray diffraction and the differential scanning calorimetry (DSC), the ketoconazole combined onto the ion-exchange fibers was in a highly molecular level dispersed state. The improved dissolution of ketoconazole ion-exchange fiber complexes is likely to originate from this ketoconazole’s highly dispersed state. Furthermore, due to this ketoconazole’s highly dispersed state, ketoconazole ion-exchange fiber complexes significantly decreased the individual difference of absorption in oral administration of ketoconazole caused by the fluctuation of the acid degree in the gastric fluid.     

The role of particle physico-chemical properties in pulmonary drug delivery for tuberculosis therapy

Abstract

There is increasing interest in the use of inhaled aerosol drug therapy for the treatment of tuberculosis (TB). A number of methods of preparation of particles have been employed including spray drying, solvent evaporation, emulsion and phospholipid methods to create microparticles, macroaggregated nanoparticles, solid lipid nanoparticles and liposomes. Each of these methods involves the use of different proportions of additives to aid in the particle formation or to achieve important physico-chemical properties such as ease of dispersion. While these approaches all have merit their practical value is limited by constraints on dose and means of delivery as an aerosol in order to achieve a therapeutic effect. A review of a number of approaches is presented and placed in the context of the need for effective aerosol delivery systems for the treatment of TB as a guide to selection of appropriate excipients, processes and delivery strategies to support product development activities.     

A new self-emulsifying formulation of mefenamic acid with enhanced drug dissolution

To enhance the dissolution of poorly soluble mefenamic acid, self-emulsifying formulation (SEF), composing of oil, surfactant and co-surfactant, was formulated. Among the oils and surfactants studied, Imwitor^® 742, Tween^® 60, Cremophore^® EL and Transcutol^® HP were selected as they showed maximal solubility to mefenamic acid. The ternary phase diagram was constructed to find optimal concentration that provided the highest drug loading. The droplet size after dispersion and drug dissolution of selected formulations were investigated. The results showed that the formulation containing Imwitor^® 742, Tween^® 60 and Transcutol^® HP (10:30:60) can encapsulate high amount of mefenamic acid. The dissolution study demonstrated that, in the medium containing surfactant, nearly 100% of mefenamic acid were dissolved from SEF within 5 min while 80% of drugs were dissolved from the commercial product in 45 min. In phosphate buffer (without surfactant), 80% of drug were dissolved from the developed SEF within 5 min while only about 13% of drug were dissolved in 45 min, from the commercial product. The results suggested that the SEF can enhance the dissolution of poorly soluble drug and has a potential to enhance drug absorption and improve bioavailability of drug.     

Evaluation of the losartan solubility in the biowaiver context by shake-flask method and intrinsic dissolution

This study aimed at evaluating the shake-flask use as a universal method to evaluate drug solubility in a biowaiver context as proposed by FDA, EMA and ANVISA. The solubility of losartan was determined in three buffers using the shake-flask method, intrinsic dissolution (ID) and Quantum Chemistry. Moreover, the evaluation of a losartan dissolution profile from coated tablets was conducted. The losartan low solubility in pH 1.2 and high solubility in pH 6.8 were observed using the shake-flask method. However, the solubility results using ID demonstrated its high solubility in pH 1.2 and 6.8. It was not possible to find conclusive results regarding the solubility of the drug in pH 4.5. The studies conducted by Quantum Chemistry provide molecular and electronic data that helped understand the losartan solvation in different pH values. Our experimental results defined that losartan can be classified as a low-solubility drug. In addition, this work shows that shake-flask cannot be a universal method of solubility studies in biowaiver context. Individual analysis will be necessary. The intrinsic dissolution should be considered as a complementary method.     

A Simulated Stomach Duodenum Model Predicting the Effect of Fluid Volume and Prandial Gastric Flow Patterns on Nifedipine Pharmacokinetics From Cosolvent-Based Capsules

Nifedipine is a Biopharmaceutics Classification System class II drug displaying large variability in absorption even when administered as immediate-release soft gelatin capsules of a cosolvent formulation. This in vitro study sought to understand the reasons behind variability in nifedipine absorption, how it can be minimized, and if it can be predicted using in vitro models. A dynamic in vitro simulated stomach duodenum model was used to explore drug concentration–time profiles of nifedipine soft gelatin capsules under conditions simulating how patients take their medicines. Specifically, the effect of prandial gastric emptying patterns and fluid volume administration (250 mL vs. 50 mL water) were investigated. Significant supersaturation of nifedipine was observed. While administration of large and small water volumes gave rise to a similar C_max and area under the curve (AUC_∞), the coefficient of variation in AUC was 4.8% and 49%, respectively, which can be attributed to differences in precipitation kinetics. Fasting and fed gastric emptying patterns also gave rise to a similar AUC; however, C_max was significantly lower in the fed state. These trends are consistent with previously published in vivo results in healthy volunteers. The simulated stomach duodenum provides a good discriminative screening tool for predicting trends in drug concentration profiles of Biopharmaceutics Classification System class II drugs.     

Liquid Oil Marbles: Increasing the Bioavailability of Poorly Water-Soluble Drugs

Many new therapeutic candidates and active pharmaceutical ingredients (APIs) are poorly soluble in an aqueous environment, resulting in their reduced bioavailability. A promising way of enhancing the release of an API and, thus, its bioavailability seems to be the use of liquid oil marbles (LOMs). An LOM system behaves as a solid form but consists of an oil droplet in which an already dissolved API is encapsulated by a powder. This study aims to optimize the oil/powder combination for the development of such systems. LOMs were successfully prepared for 15 oil/powder combinations, and the following properties were investigated: particle mass fraction, dissolution time, and mechanical stability. Furthermore, the release of API from both LOMs and LOMs encapsulated into gelatine capsules was studied.     

亲水凝胶骨架材料制备盐酸多奈哌齐缓释片的可行性研究

目的 采用亲水凝胶骨架材料制备盐酸多奈哌齐缓释片,并对其质量进行评价。方法 采用亲水凝胶骨架材料HPMC K100LV和K4M联用通过干法制粒工艺制备盐酸多奈哌齐缓释片,以溶出曲线相似性f2值作为评价指标,通过正交设计进行处方优化,用高效液相色谱法进行含量和杂质检测,通过加速和长期试验考察片剂稳定性。结果 以该方法制备的盐酸多奈哌齐缓释片质量稳定,具有与原研制剂一致的溶出特征。结论 以该方法制备盐酸多奈哌齐缓释片具有可行性。