BACKGROUND & AIMS: :Staphylococcal abscesses contain two types of lipids which are bactericidal for Staphylococcus aureus. These include a group of long chain unsaturated free fatty acids and another as yet unidentified lipid with unique properties. When abscess homogenates are incubated with S. aureus culture filtrates, the amount of bactericidal activity is increased. This phenomenon is called activation. To determine the source of increased bactericidal activity during activation, individual types of lipid were isolated from abscess homogenates and examined for their ability to be activated. Activation was found to result from the release of long chain unsaturated fatty acids from glycerides, presumably by the action of staphylococcal lipase.

背景与目标： ：葡萄球菌脓肿含有两种对金黄色葡萄球菌具有杀菌作用的脂质。这些包括一组长链不饱和游离脂肪酸和另一种尚未鉴定的具有独特性质的脂质。当脓肿匀浆与金黄色葡萄球菌培养滤液一起孵育时，杀菌活性增加。这种现象称为激活。为了确定活化过程中杀菌活性增加的来源，从脓肿匀浆中分离了各种类型的脂质，并检查了它们的活化能力。发现活化是由甘油酯释放长链不饱和脂肪酸引起的，大概是由于葡萄球菌脂肪酶的作用。

BACKGROUND & AIMS: :Gamma linolenic acid (GLA, 18:3, cis- 6,9,12- octadecatrienoic acid), an important compound in n- 6 eicosanoid family biosynthesis, occurs in the lipids of a few plant and microbial sources. This study focused on the screening of microbial strains with suitable lipase activity for enrichment of GLA by selective hydrolysis of the borage oil (21.6 % of GLA/total fatty acids). Firstly, 352 microrganisms were tested for their lipolytic capacity using screening techniques on agar plates containing borage oil, strains were then selected and screened for their activity (U/mg) using both submerged fermentation (SmF) and solid state fermentation (SSF). The rate of hydrolysis and the selective preference of these hydrolytic enzymes towards fatty acids, with a special focus on enrichment of GLA were studied and compared with those obtained by two commercially-available lipases. Only one of the lipases tested during this study displayed selectivity, discriminating the GLA during the hydrolysis reaction. Using the enzymatic extract from Geotrichum candidum as a biocatalyst of the reaction, it was possible to obtain a percentage of 41.7% of GLA in acylglycerols fraction when the borage oil was treated in a fixed-bed reactor for 24 hours at 30ºC.

背景与目标： γ亚麻酸（GLA，18：3，顺式6,6,9,12-十八碳三烯酸）是n-6类二十烷酸家族生物合成中的重要化合物，它存在于一些植物和微生物来源的脂质中。这项研究的重点是筛选具有合适脂肪酶活性的微生物菌株，以通过琉璃苣油的选择性水解（GLA /总脂肪酸的21.6％）来富集GLA。首先，在含有琉璃苣油的琼脂平板上使用筛选技术对352种微生物的脂解能力进行了测试，然后选择菌株，并通过深层发酵（SmF）和固态发酵（SSF）对其活性（U / mg）进行了筛选。研究了水解速率和这些水解酶对脂肪酸的选择性偏爱，特别侧重于GLA的富集，并将其与通过两种市售脂肪酶获得的酶进行了比较。在这项研究中测试的脂肪酶中只有一种具有选择性，在水解反应过程中可区分GLA。使用来自假丝酵母的酶提取物作为反应的生物催化剂，当将琉璃苣油在固定床反应器中于30ºC处理24小时时，可以得到酰基甘油馏分中GLA的41.7％百分比。

BACKGROUND & AIMS: :Lard obtained from the rendering of fatty porcine tissue is used in cosmetic products, as are several of its derivatives. These derivatives include Lard Glycerides (mono-, di-, and triglycerides derived from Lard), Lard Glyceride (the monoglycerides only), Hydrogenated Lard Glycerides, Hydrogenated Lard Glyceride, and Hydrogenated Lard. The latter three are produced by controlled hydrogenation of the described precursor. These ingredients function as skin-conditioning agents and, with the exception of Lard, as viscosity-increasing agents in several cosmetic products. No information was available regarding the fate during processing of impurities such as pesticides or heavy metals that may be found in animal tissue. Lard itself is established by the Food and Drug Administration (FDA) as a GRAS (generally recognized as safe) substance. Animal studies report adverse effects expected with the feeding of high fat diets, but other animal toxicity data were not available. Lard was not mutagenic in transgenic mice. Cell proliferation assays showed more proliferation in mice fed Lard compared to those fed plant-source fats, but another study showed no difference. Cocarcinogenic effects were observed when high-fat diets containing Lard were fed, with known carcinogens, to mice, rats, and hamsters. Consistent with the FDA GRAS determination, it was concluded that these ingredients may be used safely in cosmetic formulations. However, it was considered important to limit the presence of heavy metals and/or polychlorinated biphenyl (PCB) or other pesticide contamination. Accordingly, limits were established as follows: lead, not more than 0.1 ppm; arsenic (as As), < or =3 ppm; mercury (as Hg), < or =1 ppm; and total PCB/pesticide contamination, not more than 40 ppm, with not more than 10 ppm for any specific residue.

背景与目标： ：从脂肪猪组织中提炼得到的猪油及其一些衍生物也用于化妆品中。这些衍生物包括猪油甘油酯（衍生自猪油的甘油单酯，甘油二酯和甘油三酯），猪油甘油酯（仅甘油单酯），氢化猪油甘油酯，氢化猪油甘油酯和氢化猪油。后三种通过所描述的前体的受控氢化来生产。这些成分用作皮肤调理剂，除猪油以外，还用作几种化妆品中的增粘剂。没有关于动物组织中可能存在的杂质（例如农药或重金属）加工过程中命运的信息。猪油本身是由美国食品药品监督管理局（FDA）建立的一种公认的GRAS物质。动物研究报告了高脂饮食喂养可能带来的不良影响，但尚无其他动物毒性数据。猪油在转基因小鼠中没有致突变性。细胞增殖试验显示，与饲喂植物来源脂肪的小鼠相比，饲喂猪油的小鼠具有更高的增殖能力，但另一项研究表明没有差异。当将含有猪油的高脂饮食与已知致癌物一起喂食小鼠，大鼠和仓鼠时，会观察到致癌作用。与FDA GRAS的测定一致，得出的结论是，这些成分可以安全地用于化妆品配方中。但是，重要的是限制重金属和/或多氯联苯（PCB）或其他农药污染的存在。因此，限值如下：铅，不超过0.1 ppm；铅，不超过0.1 ppm。砷（以As计），≤3 ppm；汞（以Hg计），<或= 1 ppm;总PCB /农药污染，不超过40 ppm，任何特定残留物不超过10 ppm。

BACKGROUND & AIMS: PURPOSE:Assessment of the extrudability of mixtures of saturated polyglycolysed glycerides used as carriers for poorly soluble drugs. METHODS:Three different mixtures of saturated polyglycolysed glycerides were extruded in a ram extruder at different rates and using different dies. The force applied to the ram and its displacement were recorded and used to determine the "specific work of extrusion" and pursuit rheometric determinations, according to the Bagley's approach. RESULTS:As the melting range of the mixtures, or the length of the dies increased, the higher the "specific work of extrusion" observed. From the rheometric analysis, viscoelastic properties were identified and decomposed into plastic and elastic components. The elastic component contributed more to the total pressure loss, and for the majority of the cases, was higher than the plastic component. From the Bagley plot it was possible to calculate the wall shear stress (sigma w), that increased with the melting range of the materials and the shear rate applied (gamma). The viscosity (eta) decreased as the shear rate increased, reflecting a non-Newtonian behavior of the materials. Finally, materials showing lower viscosities required less work to produce the extrudates. CONCLUSIONS:This study has (a) shown the possibility of preparing extrudates from different mixtures of polyglycolysed glycerides alone in a non-aqueous environment, (b) demonstrated the usefulness of the "specific work of extrusion," and (c) revealed through the rheometric studies the viscoelastic nature of the materials quantifying the contribution of the elastic and the plastic components for the total pressure loss.

背景与目标： 用途：评估用作难溶性药物载体的饱和聚乙二醇水解甘油酯混合物的可挤出性。
方法：将三种不同的饱和多聚甘油水解甘油酯混合物以不同的速率和使用不同的模具在ram挤出机中挤出。根据Bagley的方法，记录施加在撞锤上的力及其位移，并将其用于确定“挤压的特定功”并进行流变测定。
结果：随着混合物的熔化范围或模具长度的增加，观察到的“挤出比功”越高。通过流变分析，可以识别粘弹性并分解为塑性和弹性成分。弹性成分对总压力损失的贡献更大，并且在大多数情况下高于塑料成分。根据Bagley图，可以计算壁剪切应力（σw），该应力随材料的熔化范围和施加的剪切速率（γ）而增加。粘度（η）随着剪切速率的增加而降低，反映出材料的非牛顿行为。最后，显示出较低粘度的材料需要较少的工作来生产挤出物。
结论：这项研究表明：（a）在非水环境中，仅由聚甘油水解甘油酯的不同混合物制备挤出物的可能性；（b）证明了“挤出的特殊作用”的有效性；（c）通过流变学研究了材料的粘弹性，量化了弹性和塑料成分对总压力损失的贡献。

BACKGROUND & AIMS: :The effects of propranolol or phentolamine on the metabolism of phospholipids, diacylglycerol, and triacylglycerol were studied in the bovine retina in vitro. Lipid labeling was followed during short-term incubation of intact bovine retinas with [U-14C]glycerol and [1-14C]palmitic acid. Each of these precursors was recovered in the appropriate lipid moiety. Most of the [14C]glycerol appeared progressively in triacylglycerol (TG) through the sequence from phosphatidic acid (PA) to diacylglycerol (DG). Labeled palmitate appeared in much lower quantities than labeled glycerol in all glycerolipids except phosphatidylcholine (PC). Propranolol and phentolamine greatly enhanced the [14C]glycerol specific activities of PA, phosphatidylinositol (PI), and phosphatidylserine (PS), whereas labeling in other glycerolipids was much lower than in controls. The labeling in TG with both precursors was found to be less than 50% of the control values; however, a late increase in DG labeling was observed. The effects of these drugs on broken cell preparations were also described, although lipid synthesis from labeled glycerol in these preparations was only 9% that of intact retinas. It appeared that an amphiphilic cationic structure was necessary to produce these drug effects; propranolol glycol, the hydrophobic moiety of propranolol, did not elicit the same effects. It is suggested that, among other changes, the drugs inhibited phosphatidate phosphohydrolase and redirected the flux predominantly toward PI. Support for the proposed multiple lipid effects elicited by these drugs was provided by the dual changes found in the labeling of DG.

背景与目标： ：在牛视网膜中研究了心得安或酚妥拉明对磷脂，二酰基甘油和三酰基甘油代谢的影响。在完整牛视网膜与[U-14C]甘油和[1-14C]棕榈酸短期孵育期间，进行脂质标记。这些前体中的每一种都在适当的脂质部分中回收。通过从磷脂酸（PA）到二酰基甘油（DG）的序列，大多数[14C]甘油逐渐出现在三酰基甘油（TG）中。在除磷脂酰胆碱（PC）以外的所有甘油脂中，标记的棕榈酸酯的含量均远低于标记的甘油。普萘洛尔和酚妥拉明极大地增强了PA，磷脂酰肌醇（PI）和磷脂酰丝氨酸（PS）的[14C]甘油比活性，而其他甘油脂中的标记则大大低于对照。发现两种前体在TG中的标记均小于对照值的50％。但是，观察到DG标记的增加较晚。还描述了这些药物对破碎细胞制剂的作用，尽管这些制剂中标记甘油的脂质合成仅为完整视网膜的9％。看来，两亲性阳离子结构是产生这些药物作用所必需的。普萘洛尔的疏水部分普萘洛尔二醇没有引起相同的作用。建议除其他变化外，药物抑制磷脂酰磷酸水解酶并使通量主要转向PI。 DG标记中的双重变化为这些药物引起的多种脂质效应提供了支持。

BACKGROUND & AIMS: :The Dufour's gland of Anthophora abrupta, a solitary bee, secretes a complex mixture of liquid triglycerides containing one long-chain and two shortchain fatty acids. This is applied inside the earthen brood cells and added to the provision, where it is converted, perhaps by enzymes from the bee's saliva or gut, to solid diglycerides that are later eaten by the bee larvae. This use of Dufour's gland secretion as food and its nutritive function are reminiscent of the royal jelly secreted by honey bees.

背景与目标： ：蜜蜂Anthophora abrupta的杜福尔腺分泌一种液体甘油三酸酯的复杂混合物，该混合物包含一个长链脂肪酸和两个短链脂肪酸。这被应用到土育细胞内部，并添加到食物中，在那里它可能被蜜蜂唾液或肠道中的酶转化为固体甘油二酸酯，随后被蜜蜂幼虫食用。杜福尔腺分泌物作为食物的这种用途及其营养功能使人联想到蜜蜂分泌的蜂王浆。

BACKGROUND & AIMS: :In this paper, the reaction of enzymatic trans-esterification of glycerides with ethanol in a reaction medium containing hexane at a temperature of 37 degrees C has been studied. The enzyme was Lipase from Mucor miehei, immobilized on ionic exchange resin, aimed at achieving high catalytic specific surface and recovering, regenerating and reusing the biocatalyst. A kinetic analysis has been carried out to identify the reaction path; the rate equation and kinetic parameters have been also calculated. The kinetic model has been validated by comparison between predicted and experimental results. Mass transport resistances estimation was undertaken in order to verify that the kinetics found was intrinsic. Model potentialities in terms of reactors design and optimization are also shown.

背景与目标： ：在本文中，已经研究了在37摄氏度的温度下，在含有己烷的反应介质中，甘油酯与乙醇的酶促酯交换反应。该酶是来自Mucor miehei的脂肪酶，固定在离子交换树脂上，旨在获得高催化比表面并回收，再生和再利用生物催化剂。进行了动力学分析以识别反应路径。还计算了速率方程和动力学参数。通过比较预测结果和实验结果验证了动力学模型。为了验证所发现的动力学是固有的，进行了对传质阻力的估计。还显示了在反应堆设计和优化方面的模型潜力。

BACKGROUND & AIMS: :Lipid-based formulations are a viable option to address modern drug delivery challenges such as increasing the oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs), or sustaining the drug release of molecules intended for chronic diseases. Esters of fatty acids and glycerol (glycerides) and polyethylene-glycols (polyoxylglycerides) are two main classes of lipid-based excipients used by oral, dermal, rectal, vaginal or parenteral routes. These lipid-based materials are more and more commonly used in pharmaceutical drug products but there is still a lack of understanding of how the manufacturing processes, processing aids, or additives can impact the chemical stability of APIs within the drug product. In that regard, this review summarizes the key parameters to look at when formulating with lipid-based excipients in order to anticipate a possible impact on drug stability or variation of excipient functionality. The introduction presents the chemistry of natural lipids, fatty acids and their properties in relation to the extraction and refinement processes. Then, the key parameters during the manufacturing process influencing the quality of lipid-based excipients are provided. Finally, their critical characteristics are discussed in relation with their intended functionality and ability to interact with APIs and others excipients within the formulation.

背景与目标： ：基于脂质的制剂是解决现代药物输送挑战的可行选择，例如增加水溶性差的活性药物成分（API）的口服生物利用度，或维持用于慢性疾病的分子的药物释放。脂肪酸和甘油（甘油酯）和聚乙二醇（聚氧化甘油酯）的酯是通过口服，皮肤，直肠，阴道，肠胃外或肠胃外途径使用的两大类基于脂质的赋形剂。这些基于脂质的材料越来越多地用于药物产品中，但仍缺乏对制造过程，加工助剂或添加剂如何影响药物产品中API的化学稳定性的了解。在这方面，本综述总结了与基于脂质的赋形剂一起配制时要考虑的关键参数，以预期对药物稳定性或赋形剂功能变化的可能影响。引言介绍了天然脂质，脂肪酸的化学性质及其与提取和精制过程有关的特性。然后，提供了在制造过程中影响脂质基辅料质量的关键参数。最后，讨论了它们的关键特性及其预期功能和与制剂中API和其他赋形剂相互作用的能力。

BACKGROUND & AIMS: :Specimens of either sex of the freshwater catfish, Clarias batrachus, were exposed to safe and sublethal concentrations of gamma-BHC (2 and 8 ppm) and cythion (1 and 4 ppm) for 4 weeks during different phases of annual reproductive cycle. Their effects on free fatty acids (FFA) and acyl glycerides, viz., monoglycerides (MG), diglycerides (DG), and triglycerides (TG), were studied in liver, plasma, gonads, and muscle. During the preparatory phase, both pesticides suppressed the levels of FFA and acylglycerides (MG, DG, and TG) in liver of either sex but had no effect on their levels in plasma, ovary, and muscle; however, FFA and TG were reduced in testis. Unlike the preparatory phase, in the prespawning phase different lipids responded variedly to the concentrations of both Cythion and gamma-BHC. In the female, FFA in liver and plasma was raised but in ovary and muscle it was decreased. Acylglycerides in studied tissues were also reduced except ovarian TG which was increased by both pesticides at safe concentrations. Contrary to this, in the male these lipids were raised in liver and testis. Moreover, during the spawning phase, these pesticides enhanced the hepatic FFA together with acylglycerides in the female but failed to elicit any change in their levels in the male. Plasma levels of FFA and TG were reduced in the female; however, in the male FFA was raised and TG remained unchanged. Ovarian FFA and TG were decreased and increased, respectively. During the postspawning phase, none of the lipid fractions could be affected in the male except hepatic FFA which was reduced; however, in the female TG along with FFA was decreased.

背景与目标： ：在年度繁殖周期的不同阶段，淡水cat鱼的两栖标本都被暴露于安全和致死浓度的γ-BHC（2和8 ppm）和胱硫醚（1和4 ppm）的浓度达4周。在肝脏，血浆，性腺和肌肉中研究了它们对游离脂肪酸（FFA）和酰基甘油酯（即甘油一酸酯（MG​​），甘油二酸酯（DG）和甘油三酸酯（TG））的影响。在准备阶段，两种农药均抑制了男女肝脏中FFA和酰基甘油酯（MG，DG和TG）的含量，但对血浆，卵巢和肌肉的含量没有影响。但是，睾丸中的FFA和TG降低了。与准备阶段不同，在产卵阶段，不同的脂质对Cythion和γ-BHC的浓度都有不同的反应。在女性中，肝脏和血浆中的FFA升高，但在卵巢和肌肉中的FFA降低。被研究的组织中的甘油三酸酯也减少了，但卵巢TG却被安全浓度下的两种农药所增加。与此相反，在男性中，这些脂质在肝脏和睾丸中升高。而且，在产卵阶段，这些农药在雌性动物中增强了肝FFA和酰基甘油酯，但在雄性动物中并未引起其含量变化。女性血浆中FFA和TG含量降低；但是，雄性FFA升高了，TG保持不变。卵巢FFA和TG分别降低和升高。在产卵后阶段，除了肝脏中FFA含量降低外，其他脂类成分都不会受到影响。然而，女性TG与FFA一起下降。

BACKGROUND & AIMS: :In vitro and in vivo experiments were carried out with medium-chain glycerides. In vitro, cholesterol gallstones were rapidly dissolved by medium-chain glycerides; control experiments with saline solution failed to modify the size of the stones. In vivo, medium-chain glycerides were instilled through an intraductal tube in 12 patients with retained bile duct stones. Perfusions lasted 2-10 days. After perfusion, stones disappeared in six cases, were reduced in size in one case, and remained unchanged in five cases. In five cases, nausea, vomiting, diarrhea, or pain were observed. Medium-chain glyceride infusion rapidly dissolves cholesterol gallstones, but is commonly associated with mild to severe side effects.

背景与目标： ：用中链甘油酯进行了体外和体内实验。在体外，胆固醇胆结石可通过中链甘油酯迅速溶解。用盐溶液进行的对照实验未能改变结石的大小。在体内，通过留置胆管结石的12例患者通过导管插入中链甘油酯。灌注持续2-10天。灌注后，结石消失6例，变小1例，5例保持不变。在五例中，观察到恶心，呕吐，腹泻或疼痛。中链甘油酯输注可迅速溶解胆固醇胆结石，但通常会伴有轻度至严重的副作用。

BACKGROUND & AIMS: :The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 60 PEGylated alkyl glycerides. PEGylated alkyl glycerides are mono-, di-, and/or triglycerides that have been modified with ethylene glycol repeat units (in the starting material form as epoxide). Most of the PEGylated alkyl glycerides are reported to function as skin-conditioning agents or surfactants. The Panel reviewed the available animal and clinical data as well as data from the 1999 report for the 5 polyethylene glycol (PEG) glyceryl cocoates and the 2012 report of PEGylated oils, to determine the safety of these ingredients. The Panel concluded these ingredients are safe in the current practices of use and concentration when formulated to be nonirritating; this conclusion supersedes the 1999 conclusion issued on 5 PEG glyceryl cocoate ingredients.

背景与目标： ：化妆品成分安全性专家小组（小组）评估了60种聚乙二醇化烷基甘油酯的安全性。聚乙二醇化的烷基甘油酯是单，双和/或甘油三酸酯，它们已被乙二醇重复单元（以原料形式为环氧化物）改性。据报道，大多数PEG化烷基甘油酯起皮肤调理剂或表面活性剂的作用。专家组审查了现有的动物和临床数据，以及1999年5种聚乙二醇（PEG）甘油酸酯的报告和2012年PEG化油的报告中的数据，以确定这些成分的安全性。专家组得出结论，这些成分在配制为无刺激性时，在目前的使用和浓缩实践中是安全的；该结论取代了1999年发布的关于5种PEG甘油可可酸酯成分的结论。

BACKGROUND & AIMS: :Solid dispersions (SDs) of glibenclamide (GBM); a poorly water-soluble drug and polyglycolized glycerides (Gelucire with the aid of silicon dioxide (Aerosil 200); as an adsorbent, were prepared by spray drying technique. SDs and spray dried GBM in comparison with pure GBM and corresponding physical mixtures (PMs) were initially characterized and then subjected to ageing study up to 3 months. Initial characterization of SDs and spray dried GBM by DSC and XRPD showed that GBM was present in its amorphous form (AGBM). Improvement in the solubility and dissolution rate was observed for all samples. DRIFT spectroscopy revealed presence of hydrogen bonding in SDs. During ageing study, almost no decrease of in vitro drug dissolution was observed, over the period of 3 months as compare with freshly prepared SDs. Slight crystallinity in SDs was observed in the DSC and XRPD studies during ageing. Moreover in vivo study in Swiss Albino mice also justified the improvement in the therapeutic efficacy of amorphous GBM in SDs over pure GBM. Thus, present study demonstrated the high potential of spray drying technique for obtaining stable free flowing SDs of poorly water-soluble drugs using polyglycolized glycerides carriers with the aid of silicon dioxide as an adsorbent.

背景与目标： ：格列苯脲（GBM）的固体分散体（SD）;通过喷雾干燥技术制备了水溶性差的药物和聚乙二醇化甘油酯（Gelucire，借助二氧化硅（Aerosil 200）作为吸附剂），将SD和喷雾干燥的GBM与纯GBM和相应的物理混合物（PM）进行了比较首先进行了表征，然后进行了长达3个月的老化研究，通过DSC和XRPD对SD和喷雾干燥的GBM进行了初步表征，结果表明GBM以无定形形式存在（AGBM），并观察到所有化合物的溶解度和溶解速率均有所提高DRIFT光谱显示SD中存在氢键；在老化研究中，与新鲜制备的SD相比，在3个月的时间内几乎没有观察到体外药物溶解的减少；在DSC和DSC中观察到SD的结晶度较小在衰老过程中进行XRPD研究，此外，对瑞士白化病小鼠进行的体内研究也证明了无定形GBM在SD中的治疗效果优于纯GBM。目前的研究表明，喷雾干燥技术在使用聚乙二醇化甘油酯载体和二氧化硅作为吸附剂的情况下获得水溶性差的药物的稳定自由流动SD的潜力很大。

BACKGROUND & AIMS: :Labrasol is a lipid-based self-emulsifying excipient used in the preparation of lipophilic drugs intended for oral delivery. It is mainly composed of PEG esters and glycerides with medium acyl chains, which are potential substrates for digestive lipases. The hydrolysis of Labrasol by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases was investigated in the present study. Classical human pancreatic lipase (HPL) and porcine pancreatic lipase, which are the main lipases involved in the digestion of dietary triglycerides, showed very low levels of activity on the entire Labrasol excipient as well as on separated fractions of glycerides and PEG esters. On the other hand, gastric lipase, pancreatic lipase-related protein 2 (PLRP2) and carboxyl ester hydrolase (CEH) showed high specific activities on Labrasol. These lipases were found to hydrolyze the main components of Labrasol (PEG esters and monoglycerides) used as individual substrates, whereas these esters were found to be poor substrates for HPL. The lipolytic activity of pancreatic extracts and human pancreatic juice on Labrasol(R) is therefore mainly due to the combined action of CEH and PLRP2. These two pancreatic enzymes, together with gastric lipase, are probably the main enzymes involved in the in vivo lipolysis of Labrasol taken orally.

背景与目标： ：Labrasol是一种基于脂质的自乳化赋形剂，用于制备旨在用于口服的亲脂性药物。它主要由具有中等酰基链的PEG酯和甘油酯组成，它们是消化脂肪酶的潜在底物。本研究研究了猪胰腺提取物，人胰液和几种纯化的消化脂肪酶对Labrasol的水解作用。古典人胰脂肪酶（HPL）和猪胰脂肪酶是参与饮食甘油三酸酯消化的主要脂肪酶，它们对整个Labrasol赋形剂以及甘油酯和PEG酯的分离部分均具有非常低的活性。另一方面，胃脂肪酶，胰脂肪酶相关蛋白2（PLRP2）和羧基酯水解酶（CEH）对拉布拉索尔表现出较高的比活性。发现这些脂肪酶水解用作单独底物的Labrasol的主要成分（PEG酯和甘油单酸酯），而发现这些酯是HPL的不良底物。因此，胰腺提取物和人胰液对Labrasol的脂解活性主要归因于CEH和PLRP2的联合作用。这两种胰酶以及胃脂肪酶可能​​是口服服用拉布拉索尔体内脂解的主要酶。

BACKGROUND & AIMS: :1. The specific radioactivity of [(14)C]glycerol released during the incubation of brown fat with [(14)C]glucose is much greater than that of the tissue lipid glycerol. 2. From a study of the release of [(14)C]glycerol from pre-labelled brown fat, it is concluded that the tissue contains a pool of glycerides with a higher rate of turnover than those in the main lipid store. 3. This pool contains newly synthesized glycerides, has a half-life of 25-30min and supplies about 25% of the glycerol liberated by brown fat. 4. Thus, a significant fraction of the total (14)C incorporated from glucose into brown-fat lipids is released as [(14)C]glycerol during an incubation.

背景与目标： ：1。在褐色脂肪与[（14）C]葡萄糖孵育期间释放的[（14）C]甘油的比放射性比组织脂质甘油的比放射性大得多。 2.根据对预先标记的棕色脂肪中[[14] C]甘油释放的研究，得出的结论是，组织中的甘油酯库比主要脂质库中的甘油酯转化率更高。 3.该池包含新合成的甘油酯，半衰期为25-30分钟，并提供约25％的棕色脂肪释放的甘油。 4.因此，在孵育过程中，从葡萄糖掺入褐脂脂质的总（14）C中有很大一部分作为[（14）C]甘油释放。

BACKGROUND & AIMS: OBJECTIVES:Cefuroxime axetil (CA), a poorly soluble, broad spectrum cephalosporin ester prodrug, is hydrolysed by intestinal esterase prior to absorption, leading to poor and variable bioavailability. The objective was therefore to formulate a stable amorphous solid dispersion of the drug with enhanced solubility and stability against enzymatic degradation. METHODS:Spray drying was used to obtain a solid dispersion of CA with Gelucire 50/13 and Aerosil 200 (SDCAGA), and a solid dispersion of CA with polyvinyl pyrrolidone (SDCAP); amorphous CA (ACA) was obtained by spray drying CA alone. The formulations were characterized by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy studies, and compared for solubility, dissolution and bioavailability in rats. KEY FINDINGS:SDCAP and SDCAGA showed improved solubility and dissolution profiles owing to amorphization and formation of solid dispersions with hydrophilic carriers. The improved stability of amorphous CA in solid dispersions compared to ACA alone was attributed to hydrogen bonding interactions involving the amide of CA with the carbonyl of polyvinyl pyrrolidone in SDCAP, whereas in SDCAGA the interactions were at multiple sites involving the amide and carbonyl of CA with the carbonyl and hydroxyl of Gelucire 50/13. However, SDCAGA showed superior bioavailability compared to SDCAP, ACA and CA. CONCLUSIONS:Improvement in physical stability of solid dispersions was attributed to hydrogen bonding, while improvement in bioavailability of SDCAGA compared to SDCAP, in spite of comparable solubility and dissolution profile, may be attributed to Gelucire, which utilizes intestinal esterase for lipolysis, protecting the prodrug from enzymatic degradation to its non-absorbable base form.

背景与目标： 目的：头孢呋辛酯（CA）是一种难溶的广谱头孢菌素酯前药，在吸收前会被肠道酯酶水解，导致生物利用度差且可变。因此，目的是配制具有增加的溶解度和对酶促降解的稳定性的药物的稳定的无定形固体分散体。
方法：采用喷雾干燥法得到CA与Gelucire 50/13和Aerosil 200（SDCAGA）的固体分散体，以及CA与聚乙烯吡咯烷酮（SDCAP）的固体分散体。仅通过喷雾干燥CA获得无定形CA（ACA）。通过差示扫描量热法，X射线粉末衍射，扫描电子显微镜和傅里叶变换红外光谱研究对制剂进行表征，并比较了在大鼠中的溶解度，溶解度和生物利用度。
主要发现：由于无定形和与亲水性载体形成的固体分散体，SDCAP和SDCAGA的溶解度和溶出度得到了改善。与单独的ACA相比，固体分散体中无定形CA的稳定性得到改善，这归因于SDCAP中涉及CA的酰胺与聚乙烯吡咯烷酮的羰基的氢键相互作用，而在SDCAGA中，该相互作用位于CA的酰胺和羰基的多个位点。 Gelucire 50/13的羰基和羟基。但是，SDCAGA与SDCAP，ACA和CA相比，具有更高的生物利用度。
结论：固相分散体物理稳定性的提高归因于氢键结合，尽管SDCAGA的生物利用度与SDCAP相比有所改善，尽管溶解度和溶出度相当，但归因于Gelucire，它利用肠道酯酶进行脂解，保护了前药从酶促降解到不可吸收的碱形式。