布洛芬乙酯的分子筛催化合成

消旋布洛芬乙酯作为微生物拆分消旋药物布洛芬获取ｓ（＋ ）－布洛芬的前体。今采用ＨＺＳＭ－５ 分子筛作为催化剂，消旋布洛芬与乙醇摩尔比为１∶１．２，苯为溶剂及带水剂，成功地合成了消旋布洛芬乙酯。结果表明，反应条件温和，产物容易提纯，产率达９２％ 。产物结构经ＩＲ、ＧＣ－ＭＳ、ＮＭＲ鉴定。     

Thermogravimetric characterization of chitosan/alginate microparticles loaded with different drugs

Summary  The thermal behavior of several chitosan/alginate /drug microparticle formulations containing ciprofloxacin, ibuprofen, ketoprofen or tannic acid was investigated by thermogravimetry in inert atmosphere in the temperature range of 25 – 900^oC. The chemical composition and the method used for drug incorporation influenced the thermal stability of the products. It was found that the entrapment of the drug in chitosan, alginate or chitosan/alginate complex modifies the degradation mechanism introducing new degradation steps by comparison with raw polymers. The activation energy for the main degradation step is also changed.     

Thermo‐ and pH‐sensitive hydrogels based on 2‐(2‐methoxyethoxy)ethyl methacrylate and methacrylic acid

Hydrogels based on commercially available 2‐(2‐methoxyethoxy)ethyl methacrylate (MEO₂MA), with methacrylic acid (MAA) as comonomer, are studied. The incorporation of an ionizable monomer, such as MAA, in a thermosensitive system leads to the formation of hydrogels able to respond to pH and temperature according to their monomeric composition. Thus, at low pH, the acid groups of MAA are protonated, and they do not contribute to increase the hydrophilic balance, and collapse of the hydrogels occurs around room temperature. For temperatures below that of collapse, the degree of swelling increases with increasing MEO₂MA content. In contrast, at neutral or basic pH, the ionization of the acid groups contributes to increase the hydrophilicity and the osmotic pressure, leading to polyelectrolyte behaviour. In this regime, the swelling capacity increases and the thermosensitivity decreases with increasing MAA content in the hydrogels. These properties make poly(MEO₂MA‐co‐MAA) hydrogels suitable candidates for use in oral controlled delivery of hydrophobic drugs. This possibility is explored using ibuprofen as a model drug, after a complete study of the swelling kinetics. Copyright © 2010 Society of Chemical Industry     

The Effect of Clove Oil on the Transdermal Delivery of Ibuprofen in the Rabbit by In Vitro and In Vivo Methods

The study was designed to evaluate skin permeation enhancement effect of essential oils from Eugenia caryophyllata (clove oil) in rabbits and to compare the in vitro absorption and in vivo permeation using ibuprofen as a model drug. The in vitro results indicated a significant permeation enhancement effect of the clove oil. The group with 1% oil appeared to the flux (239 μg/cm²/hr), and 3% oil was 293 μg/cm²/hr to some extent similar with 2% azone group (327 μg/cm²/hr). The enhancement ratio of clove oil was 7.3. In vivo results also demonstrated that clove oil showed a significant permeation enhancement effect, but the enhancement of clove oil was relatively weak than in vitro. The group with 3% oil exhibited the higher value of area under the curve (AUC) of 80.8 μg/mL·hr, which was 2.4 times the high of control. The AUC value of 3% oil group was similar to that of 2% azone group (89.8 μg/mL·hr). The GC-MS results indicated eugenol and acetyleugenol identified from clove oil might mainly contribute to enhance in vitro and in vivo absorption of ibuprofen because of its large quantities (90.93%).     

Initial Salt Screening Procedures for Manufacturing Ibuprofen

The aim of this paper is to design initial salt screening procedures for manufacturing ibuprofen. Salt forms of a pharmaceutical acid racemic (R,S)-(±)-ibuprofen and their “developable” synthetic routes were ferreted out simultaneously through the screening of seven bases of sodium hydroxide, potassium hydroxide, l-arginine, l-histidine, l-lysine, diethanolamine, and tris(hydroxymethyl)aminomethane (THAM), and the match with the use of nine organic solvents of methanol, dimethyl sulfoxide, ethanol, N,?N-dimethylformamide, acetonitrile, isopropyl alcohol, 1,4-dioxane, acetone, and tetrahydrofuran mainly in the presence of water in 20 mL scintillation vials. Racemic (R,S)-(±)-sodium ibuprofen dihydrate, a well-known ibuprofen salt and the newly discovered racemic (R,S)-(±)-THAM ibuprofen, appeared as white-squared powders with a molecular weight of 327.42 g/mol, a melting point of 160.17°C, and the apparent solubility product, K′_sp, of 6.0 × 10^?4 M² at 25°C were successfully synthesized by the initial salt screening methods. The new amine salt of ibuprofen was monoclinic and had a space group of P2₁/c and lattice parameters of a = 17.578(8)°, b = 10.428(4)°, c = 9.991(4) Å, α = 90.00°, β = 97.17(1)°, γ = 90.00°, and V = 1,817.05(244) ų. The aspect ratio of the amine salt crystals of ibuprofen of ≈ 1.0 implied that the crystals had a better flowability than the sodium salt counterparts. This amine salt of ibuprofen was more stable in moist or dried atmospheres and was more hydrophobic than the sodium salt of ibuprofen. Moreover, the slow dissolution of this amine salt of ibuprofen might have made it less bitter and more suitable as a sustained release drug than the sodium salt of ibuprofen. The future work is to search for the different polymorphs of this amine salt of ibuprofen and to extend the initial salt screening working logics to the formation of co-crystals.     

高效毛细管电泳-电堆积柱上富集法分离与测定5种药品中布洛芬的含量

建立高效毛细管电泳-电堆积柱上富集法分离与测定5种药品中布洛芬含量的方法。在220nm波长处以间苯二酚为内标物,分离电压为20kV,分离温度为25℃,用10mmol·L-1硼砂缓冲液(pH=9.2)作毛细管电泳的运行液,被测组分与内标物得到快速分离。布洛芬的进样浓度在10～400mg·L-1范围内与电泳峰面积呈良好的线性关系,r=0.9997,平均回收率100.9%,最低定量浓度为0.35mg·L-1。该方法简捷、快速、重现性好,可用于布洛芬药物的质量控制。     

Facile synthesis and fractal feature of pH-responsive poly(acrylic acid) hollow microspheres for ibuprofen delivery

The pH-responsive hollow poly(acrylic acid) (HPAA) microspheres with regulated cavity structure and various shell thicknesses were synthesized. Their structural parameters and textural properties were characterized by various techniques. The ibuprofen loading results indicate the good drug loading capabilities of HPAA microspheres from 13.81 to 17.18%. Their ibuprofen release properties demonstrated their good pH sensitivity and distance-controlled drug diffusion process. Specially, the small-angle X-ray scattering technique was used to suggest the surface roughness and structural irregularities of HPAA before and after drug loading and releasing. These findings clearly indicate the potential of HPAA microspheres to be used as promising candidates in drug delivery.     

Preparation of ibuprofen/lipid composite microparticles by supercritical fluid technique

Using the CO₂-and N₂-assisted atomization processes, the production of ibuprofen/lipid composite microparticles is investigated, in which the lipid includes myristic acid and tripalmitin. The produced composite particles show similar morphology to that of the purelipids obtained by the same process. In the case of the N₂-assisted process, the average size of composite particles is slightly larger than that of the pure lipid particles due to the difficulty of solidification when using N₂. In the case of the CO₂-assisted process, the average size of composite particles is slightly smaller than that of the pure myristic acid particles, but slightly larger than that of the pure tripalmitin particles. The dissolution study reveals that the drug release from the ibuprofen/myristic acid particles is enhanced in comparison with that of the unprocessed ibuprofen. For the particles produced by the N₂-assisted process, the X-ray diffraction (XRD) patterns clearly indicate the encapsulation of ibuprofen into myristic acid. The obtained ibuprofen/tripalmitin composite particles with 5% or 20% of ibuprofen (in mass) evidently show the controlled drug release: only about 20% of the drug is released in 500 min from the ibuprofen/tripalmitin composite particles consisting of 20% ibuprofen prepared by the CO₂-assisted process, and the same release is obtained from the ibuprofen/tripalmitin composite particles containing 5% ibuprofen prepared by the N₂-assisted process. __________ Translated from Modern Chemical Industry, 2007, 27(Suppl. 2): 398–402 [译自: 现代化工]     

Catalytic conversions in water. Part 5: Carbonylation of 1-(4-isobutylphenyl)ethanol to ibuprofen catalysed by water-soluble palladium–phosphine complexes in a two-phase system

1-(4-Isobutylphenyl)ethanol (IBPE) was carbonylated to 2-(4-isobutylphenyl)propionic acid (ibuprofen) in an aqueous/organic two phase system using the water-soluble Pd(tppts)₃ catalyst [tppts = P(C₆H₄-m-SO₃Na)₃] in the presence of p-CH₃C₆H₄SO₃H at 363 K, 15 MPa CO pressure and a palladium concentration of 150 ppm without addition of organic solvents. Under these conditions the conversion of IBPE was 83% and the selectivity to ibuprofen 82% with no decomposition of the Pd(tppts)₃ catalyst. Both the activity and selectivity were strongly influenced by the tppts/Pd molar ratio and the nature of the added Brønsted acid. Maximum efficiency was observed for P/Pd = 10. Acids of weakly or non-coordinating anions, such as p-CH₃C₆H₄SO₃H, CF₃COOH or HPF₆ afforded carbonylation. No catalytic activity was observed in the presence of acids of strongly coordinating anions, such as HI. The water-soluble Pd/dppps catalyst [dppps = Ar_2-nPh_nP-(CH₂)₃-PPh_n′Ar_2-n′; Ar = C₆H₄-m-SO₃Na; n = nń = 0: 86% and n = 0, nń = 1: 14%] exhibited low catalytic activity and the major product obtained was the linear isomer of ibuprofen, 3-(4-isobutylphenyl)propionic acid (3-IPPA) with selectivities up to 78%. Replacement of tppts by a ligand containing less −SO₃Na groups such as monosulphonated triphenylphosphine (tppms) gives rise to a dramatic drop in the catalytic activity and selectivity to ibuprofen. No catalytic activity was observed using palladium catalysts modified with 2-pyridyldiphenylphosphine (PyPPh₂) and tris(2-pyridyl)phosphine (PPy₃) which are both water soluble in their protonated form. A catalytic cycle is proposed to explain the observed results. ©1997 SCI     

水-有机溶剂混溶体系中催化抗体催化拆分布洛芳脂

The asymmetric hydrolysis of racemic ibuprofen ester is one of the most important methods for chiral separation of ibuprofen. In this work, a catalytic antibody that accelerates the rate of enantioselective hydrolysis of ibuprofen methyl ester was obtained against an immunogen consisting of tetrahedral phosphonate hapten attached to bovine serum albumin (BSA). The catalytic activity of the catalytic antibody in the water-miscible organic-solvent system composed of a buffer solution and N, N-dimethylformamide (DMF) was studied. With 6% DMF in the buffer solution (containing catalytic antibody 0.25 μmol, 0.2 mol•L－1 phosphate buffer, pH 8) at 37°C for 10 h, a good conversion (48.7%) and high enantiomeric excess (>99%) could be reached. The kinetic analysis of the catalytic antibody-catalyzed reaction showed that the hydrolysis in the water-miscible organic-solvent system with DMF in buffer solution followed the Michaelis-Menten kinetics. The catalytic efficiency (Kcat/Km) was enhanced to 151.91 L•mmol－1•min－1, twice as large as that for the buffer solution only.