Influence of Type and Level of Water-Soluble Additives on Drug Release and Surface and Mechanical Properties of Surelease® Films

Ethylcellulose in combination with water-soluble additives has been used in the development of microporous membrane-coated dosage forms. In the present study, application of three types of water-soluble additives, namely polyethylene glycols (PEG 400, 3350, and 8000), maltodextrins (Maltrin M150, M100, and M040 in the order of lower to higher average polymer size and molecular weight; dextrose equivalence 16.9, 11.1, and 4.8, respectively), and xylitol, as porosity modifiers in the films of a commercially available aqueous ethylcellulose dispersion (Surelease/E-7-7060 plasticized with glyceryl tricaprylate/caprate) was investigated. The effect of type and level of these additives on drug release characteristics and surface and mechanical properties of the polymeric films was studied. Each additive was incorporated at 20 and 30% levels in the polymeric dispersion based on its solids content. Ibuprofen tablets were coated using the polymeric dispersion with and without additive at 3% w/w coat level in a fluid-bed equipment. The coated tablets were evaluated for their drug release rate, coat reflectivity (gloss), Brinell hardness, and elastic modulus. Differential scanning calorimetric analysis of the films was performed to determine the physico-chemical changes in the applied film-coats. The rate of drug release, hence film porosity, was observed to be dependent on the type and level of the additive added. The molecular weight of the additive and its concentration in the polymeric dispersion had significant influence on the rate of drug release, hardness, and elasticity of the film-coats.     

Accelerated degradation of ibuprofen in tablets

The forced degradation of 11 ibuprofen tablet brands was carried out according to current industry best practices. The results indicated an incompatibility between ibuprofen and two common tablet excipients (polyethylene glycol and polysorbate 80) that were observed to accelerate the degradation of ibuprofen in tablets stored for three weeks at 70°C/75% RH. Studies of binary drug/excipient samples supported the conclusion. One degradant that was observed at increased levels was 4-isobutylacetophenone (4-IBAP), which is a known toxin.     

布洛芬注射液的研制

目的：制备布洛芬注射液,建立其质量控制方法,并考察其稳定性和安全性。方法：优化处方组成与制备工艺,并进行性状、鉴别、检查等质量研究,采用高效液相色谱法测定有关物质和含量,稳定性试验考察其稳定性,血管刺激性试验、溶血性试验以及过敏性试验评价其用药的安全性。结果：药品经酸、碱、氧化、高温、光照破坏后所产生的杂质峰均能与主峰...     

LC-MS/MS法测定布洛芬颗粒剂的人体生物等效性研究

目的研究布洛芬颗粒在健康人体内的药动学及其生物利用度,以评价其与布洛芬混悬液的生物等效性。方法 23例健康男性志愿受试者,采用随机、开放、单剂量、双周期自身交叉试验设计。分别口服布洛芬颗粒(受试制剂)与布洛芬混悬液(参比制剂)后,采用液相色谱-串联质谱(LC-MS/MS)法测定血浆中布洛芬的药物浓度。结果受试制剂与参比制剂的Cmax分别为(17.438 6±5.304 0)、(18.557 7±4.641 7)mg/L,AUC0-24分别为(59.000 3±13.935 3)、(58.506 4±16.720 2)mg/(h·L),AUC0-∞分别为(59.718 0±14.020 0)、(59.227 8±16.815 8)mg/(h·L),Tmax分别为(1.478 3±0.922 9)、(1.021 7±0.822 0)h。结论空腹口服布洛芬颗粒受试制剂与参比制剂具有生物等效性。     

Design and Evaluation of Ethyl Cellulose Based Matrix Tablets of Ibuprofen with pH Modulated Release Kinetics

Controlled release preparations have been reported to reduce the gastro irritant and ulcerogenic effects of non steroidal antiinflammatory drugs. In the present study, an attempt was made to develop matrix tablet-based controlled release formulations of ibuprofen, using ethyl cellulose as the rate-controlling polymer. In order to prevent initial release of the drug in the acidic environment of the stomach, cellulose acetate phthalate was incorporated in the matrix in varying amounts. It was found that with increasing the proportion of ethyl cellulose in the matrix, the drug release was extended for 14-16 h. Incorporation of cellulose acetate phthalate in ethyl cellulose matrix provided very low initial release of the drug in the first 2-3 h followed by enhanced release rate in alkaline medium owing to the high solubility of cellulose acetate phthalate at basic pH which led to creation of a porous matrix. It was concluded that combination of cellulose acetate phthalate with ethyl cellulose in the matrix base can be an effective means of developing a controlled release formulation of ibuprofen with very low initial release followed with controlled release up to 14-16 h.     

Optimization of ibuprofen gel formulations using experimental design technique for enhanced transdermal penetration

The aims of this study were to develop a transdermal gel formulation for ibuprofen using experimental design techniques and to evaluate its pharmacokinetic properties. The three factors chosen for factorial design were the concentrations of drug, polyoxyethylene(5)cetyl/oleyl ether and ethanol and the levels of each factor were low, medium and high. Skin permeation rates and lag times of ibuprofen were evaluated using the Franz-type diffusion cell in order to optimize the gel formulation. The permeation rate of ibuprofen significantly increased in proportion to the drug concentration, but significantly decreased in proportion to POE(5)cetyl/oleyl ether concentration. Ethanol concentration was inversely proportional to the lag time. The pharmacokinetic properties of the optimized formulation were compared with those of two marketed products in rats. The relative bioavailability of ibuprofen gel compared to the two marketed products was 228.8% and 181.0%. In conclusion, a transdermal ibuprofen gel was formulated successfully using the technique of experimental design and these results helped in finding the optimum formulation for transdermal drug release.     

Isotopic ratios to detect infringements of patents or proprietary processes of pharmaceuticals: two case studies

Because of the increasing problem of drug counterfeiting and the potential danger related as well as the economic losses involved, the pharmaceutical industry and the regulatory instances are interested in the development of anti-counterfeiting and patent protection methodologies. In this paper, the evaluation of measured isotopic ratios by means of explorative chemometric techniques was performed to distinguish groups in two data sets containing samples of acetyl salicylic acid and ibuprofen, respectively. The samples in the data sets originated from different countries and manufacturers. For both compounds a clear distinction of groups of samples could be obtained. These groups could be explained based on the origin of the samples, both geographically as well as based on the manufacturer. Hypotheses were formulated concerning the synthetic pathways of the molecules and they were linked to the groups obtained with the chemometric tools.     

布洛芬原料药及部分杂质的细胞毒性研究

摘 要 目的：评价布洛芬原料药及6种杂质的细胞毒性。方法: 不同浓度的布洛芬原料药及6种杂质作用于小鼠成纤维细胞（L929）72 h后,显微镜观察细胞毒性。结果: 在布洛芬原料药中,杂质B的细胞毒性最弱,为轻微毒性;杂质N、D、J、V细胞毒性均呈中度毒性,杂质E的细胞毒性呈现重度细胞毒性。结论:在该原料药中,同等浓度条件下,杂质E的毒性最强,应对其在布洛芬制剂中的含量进行严格地控制。