以脱氢枞胺拆分布洛芬

目的:使用脱氢枞胺拆分布洛芬,拆分得到药用价值高的(S)-型对映体;方法:当n(Am1):n(Ibupro-fen)=1:1反应时,形成酰胺;分别选择用甲醇、乙醇作为溶剂,分别结晶得到非对映异构体酰胺;酰胺在一定比例的乙酸、浓盐酸条件下冷凝回流水解;结果与结论:脱氢枞胺可以拆分消旋布洛芬,拆分得到的左、右旋布洛芬在旋光仪上测得各次的旋光值。

Preparation and Crystal Modification of Ibuprofen-Loaded Solid Lipid Microparticles

An emulsion-congealing technique is used to prepare solid lipid microparticles （SLM） containing ibuprofen with glyceryl behenate, tripalmitin and beewax as excipients. The difference of the solubility parameters between the excipients and ibuprofen are used to analyze their compatibility. Both the solubility parameter analysis and the experimental results show that glyceryl behenate is the best among the three excipients. The solid particles disperse well in aqueous phase when the drug loading reaches 10% （relative to lipid only）. Glycerides exhibit marked polymorphism and their rapid rates of crystallization accelerate the formation of metastable crystal modification. The metastable crystal modification characterizes high drug loading capacity but less stability. Increasing the content of lipophilic drug in a lipid matrix facilitates the transformation of excipients to more stable polymorphic forms.

Enhancement of UV-assisted TiO_2 degradation of ibuprofen using Fenton hybrid process at circumneutral pH

A synergistic UV/TiO2/Fenton(PCF)process is investigated for the degradation of ibuprofen(IBP)at circumneutral pH.The IBP decay in the PCF process is much faster than that with the conventional UV,UV/H2O2,Fenton,photo‐Fenton,and photocatalysis processes.The kinetics analysis showed that the IBP decay follows a two‐stage pseudo‐first order profile,that is,a fast IBP decay(k1)followed by a slow decay(k2).The effects of various parameters,including initial pH level,dosage of Fenton’s reagent and TiO2,wavelength of UV irradiation,and initial IBP concentration,are evaluated.The optimum pH level,[Fe2+]0,[Fe2+]0/[H2O2]0 molar ratio,and[TiO2]0 are determined to be approximately 4.22,0.20 mmol/L,1/40,and 1.0 g/L,respectively.The IBP decay at circumneutral pH(i.e.,6.0–8.0 for wastewater)shows the same IBP decay efficiency as that at the optimum pH of 4.22 after 30 min,which suggests that the PCF process is applicable for the treatment of wastewater in the circumneutral pH range.The lnk1 and lnk2 are observed to be linearly correlated to 1/pH0,[IBP]0,[H2O2]0,[H2O2]0/[Fe2+]0 and ln[TiO2]0.Mathematical models are therefore derived to predict the IBP decay.

Resolving Ketoprofen Using n-Octyl-d-glucamine as an Optical Resolution Agent

The process of resolution of racemic ketoprofen using n-octyl-d-glucamine as an optical resolution agent was investigated. The process consists of preparation of the diastereomer salt of ketoprofen with n-octyl-d-glucamine, liberation of S-(+)-ketoprofen from its diastereomer salt and recovery of the remaining ketoprofen and n-octyl-d- glucamine. The suitable conditions for preparation of the diastereomer salt were methanol and ethyl acetate (1.1 by volume) as the solvent, the ratio of solvent volume to ketoprofen mass at 8ml:1g, and the molar ratio of ketoprofen to n-octyl-d-glucamine at 1:1. The preferred approach to liberate S-(+)-ketoprofen from its diastereomer salt was alkali dissolution, acid adjustment and ethyl acetate extraction. Racemization of the recovered ketoprofen could be achieved by reacting the recovered ketoprofen with 10% NaOH at 507 kPa for 6h. The recovered n-octyl-d- glucamine could be refined by acid dissolution and alkali adjustment. S-(+)-ketoprofen can be obtained with high optical purity and yield, showing that the present process is a practical and efficient one which can be used in industrial scale for preparation of S-(+)-ketoprofen.

Chiral Separation of Ibuprofen by Supercritical Fluid Chromatography

The separation method using chiral stationary phase （CSP） for the preparation of enantioselective compound was widely used. In this work, supercritical fluid chromatography（SFC） was proposed to resolve the chiral mixtures. To determine the optimum operating conditions for the chiral separation of the racemic ibuprofen, the retention factors and resolutions with the change in pressure, temperature and the content of IPA （%, by volume） in supercritical CO2 were investigated. Experiments showed that the retention factor decreased with the increase of pressure and decrease in temperature. The retention factor was also influenced by the content of IPA in mobile phase, as the content of IPA in the supercritical fluid increased, the retention factor decreased. The resolution of the enantiomers became worse with the increase of IPA in the supercritical fluid. Through optimizing the experimental conditions, a SFC procedure with 13MPa, 311.15K and 4% IPA in CO2 was obtained. The peak shape of the enantiomers was symmetric with supercritical fluid chromatography when compared to the asymmetric peak shape obtained by the conventional liquid chromatography. This work demonstrated that the developed supercritical fluid chromatography procedure was suitable for the chiral separation of ibuprofen enantiomers.

Comparative Optical Separation of Racemic Ibuprofen by Using Chiral Stationary Phase

Ibuprofen is widely used as a non-steroidal anti-inflammatory drug and produced as racemic mixture. Its pharmacological activity resides only in S-(+)-enantiomer, and R-()-enantiomer is not only inactive but also has many side effects. Thus it is necessary to separate R-enantiomer from racemic ibuprofen. We studied optical separation of racemic Ibuprofen with chiral high performance liquid chromatography (HPLC). Out of three different chiral stationary phases, which were selected on the basis of structure and availability, two were found to be ef-fective. There was optimum eluent composition for each stationary phase for good resolution in optical separation. Resolution decreased with increase of eluent flow rate, but effect of injection volume on resolution was insignificant at high eluent flow rate.

Ibuprofenβcyclodextrin Inclusion Complex: Preparation, Characterization, PhysicoChemical Properties and In vitro Dissolution Behavior

Inclusion complexation between ibuprofen (IBF) and βcyclodextrin (βCD) was investigated. Phase solubility studies of the complexation suggested the formation of a 1:3 complex and a 2:3 complex between IBF and βCD at room temperature (23℃) and at 37℃ respectively. Solid inclusion complexes were prepared by the homogeneous coprecipitation method. Scanning electron microscopy, differential scanning calorimetry, IR spectroscopy, and Xray diffractometry were used for the characterization and evaluation of the complexes. The solubility and dissolution rate of the complexes formed were found to have improved considerably over that of the physical mixture and the drug alone, indicating that βcyclodextrin played an important role in the solubilization of ibuprofen.

Separation and characterization of degradation/interaction products of codeine phosphate in ibuprofen arginate/codeine phosphate combination formulation by HPLC coupled with MS analysis

A simple HPLC method was developed and validated according to the ICH guidelines to detect and quantify the related substances of codeine phosphate in the raw material and in its combination formulation with ibuprofen before and after forced degradation. These products were further identified by using HPLC-TOF/MS and MS/MS techniques. Good separations were obtained on a C18 （250 min×4.6 mm, 5 μm） column maintained at 50 ℃ with linear gradient elution by a mixture of mobile phase A （ammonium acetate （pH 6.0 regulated with acetic acid, 0.04 M）-acetonitrile （92：8, v/v）） and mobile phase B （acetonitrile） at a flow rate of 1 mL/min. UV detection was set at 245 nm. Codeine was found to be instable under oxidation with the production of mainly two stereoisomers of codeine N-oxide. A new degradation product, not reported previously, was detected under alkaline hydrolysis, which was identified as 6-hydroxy-3-methoxy-17-methyl-7,8-didehydromorphinan-5-ol and shortly named as deshydrolevomethorphandiol. The esterification of codeine by ibuprofen occurred in very small amount and only under acidic stress. These results contribute to the understanding of the degradation behavior of codeine and its interaction with ibuprofen. The developed method is sensitive and precise and could be applied for the quality control of codeine bulk drug, preparations of codeine phosphate, and its combination with ibuprofen.

Acupuncture for Primary Dysmenorrhea: A Randomized Controlled Trial

Objective： To observe the clinical therapeutic effects of acupuncture treatment for primary dysmenorrhea. Methods： 122 cases of primary dysmenorrhea were randomly divided into three groups. Fifty-two cases in the acupuncture group were treated with acupuncture. Forty cases in the medication group were treated with oral administration of Ibuprofen. Thirty cases in the placebo group were treated with oral administration of vitamin B1. The therapeutic effects were observed after treatments for three menstrual cycles. Results： The total effective rate was 96.2% in the acupuncture group, 80.0% in the medication group and 13.3% in the placebo group. By statistical management, the differences among the acupuncture group, the medication group, and placebo group were statistically significant （P〈0.05）. Conclusion： Both acupuncture and western medication are effective for primary dysmenorrhea and acupuncture treatment is better than Ibuprofen

Analysis of alternation with ibuprofen and acetaminophen in outpatient and emergency departments of a children’s hospital

In the present study,we retrospectively analyzed 105382 prescriptions of antipyretic drugs for children(0–14 years of age)in the outpatient and emergency departments of Ningbo Women and Children’s Hospital from January to December 2019.Ibuprofen and acetaminophen are relatively safe and the most commonly used drugs in daily life.Due to different dosage forms,there are acetaminophen suspension drops,acetaminophen oral solution,ibuprofen suspension,and ibuprofen suppositories for children.Through investigation,we found that the age of antipyretic drugs used by children in our hospital ranged from 3 months to 14 years old,which could be divided into two groups:single drug use and alternating use of ibuprofen and acetaminophen,with an alternating use rate of 3.19%.There were differences between the two groups in terms of age,gender,the proportion of emergency departments use,and the amount of single prescription(P<0.05).The age of the alternating use group was younger,and the male proportion,the proportion of emergency departments use,single prescription amount of the alternating use group were higher.In the alternating use group,ibuprofen and acetaminophen of different dosage forms were used alternatively.After pair comparison analysis,they only had an age difference(P<0.008),which was in line with the principle that different dosage forms are suitable for different ages.The method of alternation with ibuprofen and acetaminophen is mainly used in the emergency departments and children of younger age because most of the children have a refractory fever,which is complicated and changes relatively fast.There was no record of adverse reactions about alternation of ibuprofen and acetaminophen in the software system of adverse reactions.However,this study was a retrospective analysis,and there were risks of missing records.Therefore,alternating use of ibuprofen and acetaminophen still couldn’t ignore the risk of adverse reactions.