Solutol HS-15
(Synonyms: Polyethylene glycol 12-hydroxystearate) 目录号 : GC30012
Solutol HS-15是一种经过临床批准的辅料，具有神经保护作用。
Cas No.:61909-81-7
Sample solution is provided at 25 µL, 10mM.
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| Cell experiment [1]: | |
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Cell lines |
Rat hepatocytes |
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Preparation Method |
Hepatocytes were isolated from the in situ perfusion of a whole liver from male Wistar rats. The uptake of colchicine into the cells was determined using a centrifugal filtration technique through a silicone oil layer. These samples were incubated either in the presence or in the absence of Solutol HS 15 at different concentrations (0.0003, 0.003, and 0.03%, w/v) |
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Reaction Conditions |
0.0003, 0.003, and 0.03%, w/v |
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Applications |
Solutol HS-15 did not impact the uptake of colchicine. At a Solutol HS 15 concentration above its CMC (0.03%, w/v), the amount of colchicine taken up into the cells as well as its uptake velocity were significantly decreased. At 4 °C, a temperature at which active transport processes should be significantly slowed down, Solutol HS 15 at 0.03% did not affect colchicine uptake and/or its association with the cells. |
| Animal experiment [2]: | |
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Animal models |
Rat (MCAO and ACA models of ischemia) |
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Preparation Method |
Solutol HS 15 and dimethyl sulfoxide were dissolved in sterile saline (0.9 % NaCl). 600ml microliters of Solutol HS 15 was heated to 37 °C and dissolved in 1.4 mL of sterile saline to achieve 2 ml/kg injected (IV bolus or IP, daily for 14 days) into the rat used in MCAO and ACA models of ischemia. |
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Dosage form |
2 ml/kg IV bolus or IP, daily for 14 days |
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Applications |
Solutol HS-15 (2 ml/kg, IP) was injected chronically for 14 days (once daily). For focal ischemia experiments, Solutol HS-15 was administered following reperfusion after 2 h of middle cerebral artery occlusion (MCAO). Following ACA, the number of surviving hippocampal neurons was enhanced by Solutol-treated HS15 (68 %) rats as compared to ACA only-treated groups. Infarct volume was decreased by Solutol HS-15 (78 %) as compared to saline (vehicle) in MCAO-treated animals. Solutol HS-15 provide robust neuroprotection in both paradigms of ischemia. |
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References: [1]. GonzÁlez R C B, Boess F, Durr E, et al. In vitro investigation on the impact of Solutol HS 15 on the uptake of colchicine into rat hepatocytes[J]. International journal of pharmaceutics, 2004, 279(1-2): 27-31. |
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Solutol HS-15 , a clinically approved excipient, has neuroprotective properties[1,2]. Solutol HS 15 (polyoxyethylene esters of 12-hydroxystearic acid) is non-ionic surfactant, with low toxicity in vivo, was shown to reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug-sensitive KB 3-1 cells[3]. Solutol HS-15 also acts as a permeability enhancer[4].
Solutol HS 15 produced a 35-, 28-, and 42-fold reduction in the resistance of KB 8-5-11 cells to colchicine, vinblastine, and doxorubicin, respectively,at a concentration of 10% of its own IC50 (mean concentration of drug that causes 50% inhibition of cell growth compared to controls). Like verapamil, Solutol HS 15 promoted a 50-fold accumulation of rhodamine 123 in KB 8-5-11 cells, as measured by flow cytometry. Also, Solutol HS 15 and verapamil reduced the efflux of rhodamine 123 from KB 8-5-11 cells previously loaded with rhodamine 123 to a similar low rate. Solutol HS 15 did not affect the transport of alanine or glucose into KB 8-5-11 cells, indicating that its effect upon membrane active transport is not entirely nonspecific.
Solutol HS 15 is a third generation surfactant carrier used to improve the solubility and bioavailability [5,6]. Solutol HS 15 was the most effective to increase the solubility of Pioglitazone HCl by approximately 33 fold whereas Cremophor RH 40 increased approximately 27 folds. Suitability of Solutol HS 15 has earlier been demonstrated with its physiological compatibility and safety [7].There was simultaneous increase in concentration of micelles along with increase in concentration of Solutol HS 15, because the concentration of Solutol HS 15 used in this study was higher than its critical micelle concentration [8]. This study revealed that Solutol HS 15 is an effective carrier in enhancing solubility and stability of the Pioglitazone HCl. [9]
Solutol HS 15 merits consideration as a potential therapeutic agent because of its effectiveness for reversing multidrug resistance in vitro and its low toxicity in vivo. With proper timing and dosage, administration of Solutol HS-15 can be an effective therapy against cerebral ischemia. Following ACA, the number of surviving hippocampal neurons was enhanced by Solutol-treated HS15 (68 %) rats as compared to ACA only-treated groups. Infarct volume was decreased by Solutol HS-15 (78 %) as compared to saline (vehicle) in MCAO-treated animals. Solutol HS-15 provide robust neuroprotection in both paradigms of ischemia. This may prove therapeutically beneficial since Solutol HS-15 is already administered as a solublizing agent to patients.
References:
[1]. Lin H W, Saul I, Gresia V L, et al. Fatty acid methyl esters and Solutol HS 15 confer neuroprotection after focal and global cerebral ischemia[J]. Translational stroke research, 2014, 5(1): 109-117.
[2]. Ku S, Velagaleti R. Solutol HS-15 as a novel excipient[J]. 2010.
[3]. Coon J S, Knudson W, Clodfelter K, et al. Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance[J]. Cancer research, 1991, 51(3): 897-902.
[4]. Shubber S, et al. Mechanism of mucosal permeability enhancement of CriticalSorb? (Solutol? HS15) investigated in vitro in cell cultures. Pharm Res. 2015 Feb;32(2):516-27.
[5].Shamma RN, Basha M. Soluplus: A novel polymeric solubilizer for optimization of Carvedilol solid dispersions: Formulation design and effect of method of preparation. Powder Technol 2013;237:406-14.
[6].Song CK, Yoon IS, Kim DD. Poloxamer-based solid dispersions for oral delivery of docetaxel: Differential effects of F68 and P85 on oral docetaxel bioavailability. Int J Pharm 2016;507(1-2):102-8.
[7].Han HK, Lee BJ, Lee HK. Enhanced dissolution and bioavailability of biochanin A via the preparation of solid dispersion: In vitro and in vivo evaluation. Int J Pharm 2011;415(1-2):89-94.
[8].Bravo GonzÁlez RC, Boess F, Durr E, Schaub N, Bittner B. In vitro investigation on the impact of Solutol HS 15 on the uptake of colchicine into rat hepatocytes. Int J Pharm 2004;279(1-2):27-31.
[9]. Swain R P, Subudhi B B, Ramesh P. Effect of Solutol HS 15 in Solid Dispersions of Pioglitazone Hydrochloride: in vitro and in vivo Evaluation[J]. Indian Journal of Pharmaceutical Sciences, 2019, 81(2): 317-325.
Solutol HS-15是一种经过临床批准的辅料，具有神经保护作用。它是一种非离子表面活性剂，化学名称为12-羟基硬脂酸聚氧乙烯酯（polyoxyethylene esters of 12-hydroxystearic acid），在体内毒性低，并能够完全逆转KB 8-5和KB 8-5-11人类表皮样癌细胞的多药耐药性，在敏感的KB 3-1细胞中不会增强药物毒性。此外，Solutol HS-15还可以作为渗透增强剂。
Solutol HS 15可以在其IC50的10%浓度下，分别使KB 8-5-11细胞对秋水仙碱、长春新碱和多柔比星的抗药性降低35倍、28倍和42倍。与维拉帕米类似，Solutol HS 15通过流式细胞术测量，在KB 8-5-11细胞中促进了罗丹明123的50倍积累。此外，Solutol HS 15和维拉帕米将预先装载有罗丹明123的KB 8-5-11细胞从中排出罗丹明123到相似低速率。 Solutol HS 15不影响丙氨酸或葡萄糖进入KB 8-5-11 细胞，表明它对膜活性转运作用并非完全无特异性。
Solutol HS 15是一种第三代表面活性剂载体，用于提高溶解度和生物利用度。使用Solutol HS 15可以将Pioglitazone HCl的溶解度提高约33倍，而Cremophor RH 40只能增加约27倍。此前已经证明了Solutol HS 15具有生理相容性和安全性。随着Solutol HS 15浓度的增加，胶束浓度也同时增加，因为本研究中使用的Solutol HS 15浓度高于其临界胶束浓度。该研究揭示了Solutol HS 15在提高Pioglitazone HCl的溶解度和稳定性方面是一种有效的载体。
Solutol HS 15是一种潜在的治疗药物，因为它在体外可以有效地逆转多药耐药性，并且在体内毒性较低。通过正确的时间和剂量，给予Solutol HS-15可以成为对抗脑缺血的有效治疗方法。 ACA后，与仅接受ACA处理组相比，接受Solutol-treated HS15（68％）处理的大鼠存活海马神经元数量增加了。 MCAO处理动物中，与盐水（载体）相比，Solutol HS-15减少了梗死面积（78％）。 Solutol HS-15在两种缺血范式中都提供强有力的神经保护作用。这可能会证明具有治疗上的益处，因为已将Solutol HS-15作为溶解剂给予患者使用。
| Cas No. | 61909-81-7 | SDF | |
| 别名 | Polyethylene glycol 12-hydroxystearate | ||
| Canonical SMILES | CCCCCCC(O)CCCCCCCCCCC(OCCO)=O.[n] | ||
| 分子式 | (C2H4O)nC18H36O3 | 分子量 | |
| 溶解度 | Water : 25 mg/mL | 储存条件 | Store at 4°C, sealed storage, away from moisture |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Mechanistic study of solubility enhancement of nifedipine using vitamin E TPGS or Solutol HS-15
Drug Deliv 2006 May-Jun;13(3):201-6.16556572 10.1080/10717540500316094
The objective of our study was to find mechanisms responsible for solubility enhancement of nifedipine in solid dispersions of vitamin E TPGS and/or Solutol HS-15. Solid dispersions of nifedipine with selected polymers such as vitamin E TPGS, Solutol HS-15, PEG(1,000), and lipocol C-10 of varying drug/polymer ratios were prepared by a fusion method. The solubility enhancement was found to be in the order of vitamin E TPGS > Solutol HS-15 > lipocol C-10 > PEG(1,000). Lipocol C-10, with a similar hydrophilic-lipophilic value as vitamin E TPGS, showed a comparable retained solubility enhancement during saturation solubility studies but had lower dissolution profile. Overall, vitamin E TPGS showed the best solubility and dissolution performance, while Solutol HS-15 and lipocol C-10 demonstrated moderate solubility enhancements. Solid dispersions of vitamin E TPGS as prepared by microfluidization technique initially showed slightly higher solubility compared with samples prepared by fusion method, but eventually it became the same as the study progressed. However, solid dispersion of Solutol HS-15 as prepared by microfluidization demonstrated a significant, sustained increased in solubility over its sample when prepared by fusion method. Based on these results, we concluded that enhanced solubility using vitamin E TPGS and Solutol HS-15 resulted from a partial conversion of crystalline drug to the amorphous form, increase in wettability of the drug by water soluble polymers, better separation of drug particles, micellar solubilization of drug by high concentrations of surfactant polymers, and interaction between polymer and drug at the molecular level.
In situ controlled crystallization as a tool to improve the dissolution of Glibenclamide
Int J Pharm 2012 May 30;428(1-2):118-20.22426322 10.1016/j.ijpharm.2012.02.046
For pharmaceutical purpose, micro-sized drugs are needed for many delivery systems, such as pulmonary and oral drug delivery systems. Many strategies have been employed to reduce the particle size of poorly water soluble drugs. Microcrystals could be produced by controlled association of drug in order to obtain naturally grown particles. The aim of this work was to increase the aqueous solubility and dissolution of Glibenclamide. The in situ controlled crystallization process was conducted in the presence of the non-ionic surfactants, Cremophor RH40 and Solutol HS-15 (0.75 and 1.5%, w/v), as protective stabilizing agents against agglomeration. In addition, these surfactants inhibit P-glycoprotein that reduces intestinal absorption of Glibenclamide by efflux transportation. Crystal shape was changed and particle size was reduced by about 15-folds, compared to control untreated drug. Differential Scanning Calorimetry (DSC) results indicated no interaction between the drug and the stabilizer. Microcrystals showed marked increase in the drug dissolution, Solutol HS-15 at 1.5% (w/v) concentration showing the highest dissolution efficiency. It could be concluded that in situ controlled crystallization using surfactants are promising method to improve dissolution of Glibeclamide as a model poorly water soluble drug.
Development and evaluation of nitrendipine nanoemulsion for intranasal delivery
J Biomed Nanotechnol 2009 Feb;5(1):62-8.20055107 10.1166/jbn.2009.031
The clinical efficacy of Nitrendipine (NDP), a potent antihypertensive molecule, is limited due to its low oral bioavailability (10% to 20%) resulting from its extensive first-pass metabolism. The purpose of the present investigation was to enhance the bioavailability of NDP through formulating a nanoemulsion for its intranasal delivery. A Caproyl 90 based nanoemulsion sytem with Tween 80 as the surfactant, Transcutol P and Solutol HS-15 as solubiliser and cosurfactant respectively, was developed. A single isotropic region, which is considered as a bicontinuous nanoemulsion, was identified in the pseudo-ternary phase diagrams developed at various Tween 80: Transcutol P: Solutol HS-15 ratios. NDP was solubilized in a system consisting of Tween 80: Transcutol P: Solutol HS-15 at 1:2:1 weight ratio. The developed nanoemulsion was safe for nasal administration as confirmed by nasal histopathlogy studies with the mean globule size of 98.50 nm. The drug content per actuation was found to be 99.58 +/- 0.05%, with no significant changes over a period of one month. In vivo absorption studies revealed that NDP absorption from the nanoemulsion had a rapid onset of action and a relative bioavailability of 60.44%, significantly greater than the marketed oral tablets.
Self-nanoemulsifying drug delivery system of bruceine D: a new approach for anti-ulcerative colitis
Int J Nanomedicine 2018 Sep 28;13:5887-5907.30319255 PMC6167998
Background: Bruceine D (BD) is a major bioactive component isolated from the traditional Chinese medicinal plant Brucea javanica which has been widely utilized to treat dysentery (also known as ulcerative colitis [UC]). Methods: To improve the water solubility and absolute bioavailability of BD, we developed a self-nanoemulsifying drug delivery system (SNEDDS) composing of MCT (oil), Solutol HS-15 (surfactant), propylene glycol (co-surfactant) and BD. The physicochemical properties and pharmacokinetics of BD-SNEDDS were characterized, and its anti-UC activity and potential mechanism were evaluated in TNBS-induced UC rat model. Results: The prepared nanoemulsion has multiple beneficial aspects including small mean droplet size, low polydispersity index (PDI), high zeta potential (ZP) and excellent stability. Transmission electron microscopy showed that nanoemulsion droplets contained uniform shape and size of globules. Pharmacokinetic studies demonstrated that BD-SNEDDS exhibited enhanced pharmacokinetic parameters as compared with BD-suspension. Moreover, BD-SNEDDS significantly restored the colon length and body weight, reduced disease activity index (DAI) and colon pathology, decreased histological scores, diminished oxidative stress, and suppressed TLR4, MyD88, TRAF6, NF-κB p65 protein expressions in TNBS-induced UC rat model. Conclusion: These results demonstrated that BD-SNEDDS exhibited highly improved oral bioavailability and advanced anti-UC efficacy. In conclusion, our current results provided a foundation for further research of BD-SNEDDS as a potential complementary therapeutic agent for UC treatment.
Novel aqueous nano-scaled formulations of oleic acid stabilized hydrophobic superparamagnetic iron oxide nanocrystals
Drug Dev Ind Pharm 2013 Feb;39(2):186-96.22416888 10.3109/03639045.2012.665927
Background: Novel aqueous nano-scaled formulations were developed for hydrophobic oleic acid stabilized monodisperse superparamagnetic magnetite nanocrystals. Methods: In the study, single and mixed lipid amphiphiles based on Cremophor RH-40 (Crem-RH-40), Solutol HS-15 (Sol-HS-15), Phospholipon-100H (PL-100H) and sucrose ester M-1695 (SE-M-1695) were employed at varying concentrations. Isotonicity and physiological pH adjustments were achieved by using 5% w/v mannitol in 10 mM pH 7.4 phosphate buffer. Mannitol also served as lyoprotectant for the freeze drying of selected formulation. The developed formulations were characterized by photon correlation spectroscopy (PCS) and asymmetric flow field flow fractionation methods for their size and size distributions and morphologies were examined by transmission electron microscopy (TEM). Moreover, the potential magnetic resonance imaging (MRI) contrast agent application of a selected formulation was investigated by (1)H-NMR relaxometric measurements. Results: The results showed that stable formulations of the nanocrystals with hydrodynamic diameters generally below 100 nm were obtained. Among the developed formulations, the one prepared with 0.75% Crem-RH-40, 0.5% PL-100H and 0.25% SE-M-1695 had a mean hydrodynamic diameter of ~64 nm and zeta potential of -20 mV. This formulation exhibited low degree of aggregation, high level of incorporation of magnetite nanocrystals and very good stability profile over a period of 6 months. In addition, it showed transverse and longitudinal relaxivities of 221.8 and 32.1 s(-1)·mM(-1), respectively with r(2)/r(1) ratio of 6.9. Conclusion: This study revealed that mixed lipid-based amphiphiles allow stable aqueous formulations of the normally challenging hydrophobic magnetite nanocrystals with potential in vivo MRI contrast applications.