Isostearyl Alcohol Research Articles

In vitro and in vivo evaluation under finite conditions of a transdermal oil-in-water type emulsified formulation of propiverine hydrochloride.

A transdermal oil-in-water type emulsified formulation containing propiverine hydrochloride, used for treatment of an overactive bladder (OAB), was evaluated for in vitro skin permeation under finite conditions and in vivo transdermal absorption. Propiverine hydrochloride solubility was determined using 1,3-butyleneglycol, polyoxyethylene (2) oleylether, isostearyl alcohol, and lauryl alcohol. The solubility increased as the solubility parameter value increased. In vitro skin permeation in hairless mouse skin and in vivo transdermal absorption in rats were measured using propiverine hydrochloride dissolved in a simple solution containing these solvents. Dependent on the increase in in vitro flux, the in vivo area under the curve up to 72 h (AUC0-72) was increased. Therefore, the emulsified formulation was prepared containing these ingredients using polyoxyethylene (20) stearylether for optimization. The emulsified formulation was used to conduct in vivo single- and repeated-dose absorption studies in rats. After single-dose transdermal administration of the emulsified formulation, the AUC0-72 was equivalent to that of the simple solution. Furthermore, results using the emulsified formulation indicated an increase in AUC0-72 and significant extension of the elimination half-life, in comparison with oral administration. After repeated-dose administration, a significant minimum plasma concentration was observed compared with oral administration. These results demonstrate that the emulsified formulation is a good option for transdermal delivery of propiverine hydrochloride.

Synthesis and physical properties of new estolide esters

Vegetable oil-based oils usually fail to meet the rigorous demands of industrial lubricants by not having acceptable low temperature properties, pour point (PP) and/or cloud point (CP). Oleic estolide was produced from oleic fatty acid and a catalytic amount of perchloric acid. The oleic estolide was then esterified with a series of 16 different alcohols that were either branched or linear-chained. The new estolide esters physical properties were recorded and evaluated as a potential industrial lubricant. The linear-chain esters had higher low temperature properties (PP=−9 to −33°C) but still compete well with other commercial bio-based materials. The oleic estolide ethyl ester yielded the best PP at −33°C for the linear-chain series. The branched alcohol produced the best PP (−24 to −39°C) and CP (−30 to <−50°C) with the best PP performers being a 2-hexyldecanol (Jarcol I-16) sample, a 16 carbon-chained branched material, and 2-octyldodecanol (Jarcol I-20), a 20 carbon branched material, with a PP at −39°C. The best CP performers from the same series were the 2-octyldodecanol, with a CP lower than −50°C followed by the 2-hexyldecanol at −42°C. The viscosities (55–209cSt @ 40°C) and viscosity indexes (VIs) (169–192) performed well. The iso-stearyl alcohol (Oxocol 180) sample had the highest viscosity at 40°C of 209.3cSt which was higher than all other materials tested. Finally, these new estolide esters required no additives in order to obtain the improved performance in low temperature physical properties, thus limiting our impact on the environment and replacing fluids that are based on non renewable resources.

Drug release from hydroethanolic gels. Effect of drug's lipophilicity (log P), polymer–drug interactions and solvent lipophilicity

We demonstrate drug release properties from hydroethanolic formulations as a function of the drug's lipophilicity (log P), solvent lipophilicity and drug–polymer interactions, for the first time. A hydrophilic polymer, hydroxypropyl cellulose (HPC), provides the non-Fickian slower release of the lipophilic drug, lidocaine (log P = 2.6) and the burst (Fickian) release of hydrophilic drug, lidocaine hydrochloride (log P ≤ 0). Thus, log P of drugs helps predict the drug release properties. Hydrophobic Eudragit polymers provided the burst release of lidocaine. However, the cationic hydrophobic polymer (Eudragit E100) retained more lidocaine (∼50%) topically than other hydrophobic polymers: Eudragit S100 (anionic) and Eudragit RLPO (cationic copolymer with quaternary ammonium group) (∼25% lidocaine retention) which release lidocaine systematically. Thus, minute changes in functional groups of hydrophobic polymers help tune the lidocaine release topically or systemically. An interaction between HPC and lidocaine as determined by FTIR helps the non-Fickian slower lidocaine release from HPC formulations. However, no interactions between lidocaine and hydrophobic Eudragit polymers explain the Fickian burst release of lidocaine from their formulations. A lipophilic solvent, isostearyl alcohol which when replacing ethanol by 30%, slows the release rate and enhances the topical adsorption of lidocaine. Thus, solvent lipophilicity also modulates drug release properties.

Architecture of a Biocompatible Supramolecular Material by Supersaturation-Driven Fabrication of its Fiber Network

The architecture of a biocompatible organogel formed by gelation of a small molecule organic gelator, N-lauroyl-L-glutamic acid di-n-butylamide, in isostearyl alcohol was investigated based on a supersaturation-driven crystallographic mismatch branching mechanism. By controlling the supersaturation of the system, the correlation length that determines the mesh size of the fiber network was finely tuned and the rheological properties of the gel were engineered. This approach is of considerable significance for many gel-based applications, such as controlled release of drugs that requires precise control of the mesh size. A direct cryo-transmission electron microscopy (TEM) imaging technique capable of preserving the network structure was used to visualize its nanostructure.

SMGA gels for the skin permeation of haloperidol

Small molecule gelling agent (SMGA) gels were developed using the gelator GP-1 in the solvents, namely, isostearyl alcohol (ISA) and propylene glycol (PG), to deliver haloperidol through the skin. The concentrations of the drug, haloperidol, the enhancer, farnesol and the gelator, GP-1 are 3 mg/ml, 5% (w/v) and 5% (w/v), respectively. The study employed a three-factor full factorial statistical design to investigate the influence of factor level changes on the permeability coefficient and permeation lag-time of haloperidol. Gels were prepared by raising temperature to 120 °C, followed by natural cooling under room temperature of 22 ± 1 °C. The rheological properties of the gels were examined with a strain-controlled dynamic mechanical method. The in vitro permeation study was conducted with automated flow-through type cells. The gels successfully incorporated the drug and enhancer without losing their aesthetic properties. The in vitro human skin permeation study showed the permeation of the drug in ISA-based gels reached the pseudo steady state faster than PG-based gels and were less affected by gelator. PG-based gels delivered the drug at a faster rate with the incorporation of the enhancer. GP-1 did not influence the drug permeation rate but it increased permeation lag-time. The co-existence of gelator or enhancer increased the lag-time to a larger extent than when used separately. The novel SMGA gels are suitable for topical or transdermal delivery.

Final Report on the Amended Safety Assessment of Diisopropyl Dimer Dilinoleate, Dicetearyl Dimer Dilinoleate, Diisostearyl Dimer Dilinoleate, Dioctyl Dimer Dilinoleate, Dioctyldodecyl Dimer Dilinoleate, and Ditridecyl Dimer Dilinoleate

Diisopropyl Dimer Dilinoleate, Dicetearyl Dimer Dilinoleate, Diisostearyl Dimer Dilinoleate, Dioctyl Dimer Dilinoleate, Dioctyldodecyl Dimer Dilinoleate, and Ditridecyl Dimer Dilinoleate are diesters of their respective alcohols and dilinoleic acid. They function as skin-conditioning agents in a variety of cosmetic products at concentrations around 10%, but may be used at concentrations up to 53% in lipsticks. These ingredients do not absorb radiation in the ultraviolet (UV) UVA or UVB range and the only impurities expected are <0.5% dilinoleic acid, <0.1% isopropyl alcohol or <1% isostearyl alcohol, and/or small amounts of dilinoleic acid and cetearyl alcohol or octyldodecanol, depending on which diester is used. The potential skin penetration of these ingredients was evaluated using an estimate of the octanol/water partition coefficient (logP of 17.7) based on the structure of Diisopropyl Dimer Dilinoleate. This is consistent with the insolubility of these ingredients in water. Safety test data on dilinoleic acid (no adverse effects) were considered relevant because dilinoleic acid is a component of these diesters and a likely breakdown product. The acute oral and dermal LD(50) values for rats of Diisopropyl, Diisostearyl, and Dioctyldodecyl Dimer Dilinoleate were >5.0 g/kg. In a subchronic feeding study, macrophage aggregation was seen in the mesenteric lymph node at the lowest dose level (0.1% in the diet). These ingredients did not produce skin or ocular irritation in animal tests, nor were they comedogenic. Ames testing, clastogenesis in human lymphocytes in culture, and L5178Y mouse lymphoma cell forward mutations were all negative, indicating no dilinoleic acid genotoxicity. No carcinogenicity or reproductive/developmental toxicity data were available; however, structural alerts that would suggest a mutagenic or carcinogenic risk are absent. Significant reproductive/developmental toxicity or other systemic toxicity is not expected with these ingredients because they remain on the skin surface. In clinical studies, cosmetic formulations containing these ingredients did not produce skin irritation or sensitization, although one report of sensitization to dilinoleic acid appeared in the case literature. The Panel did note that the concentration of use of Diisopropyl Dimer Dilinoleate was reportedly as high as 53% in lipsticks, but that the highest concentration tested for irritation/sensitization is 27%. Given the size of these molecules, their relative insolubility in water, their lipophilic nature, and the absence of any significant case reports of allergic reactions, a use concentration of 53% is not likely to be associated with any adverse effects. Accordingly, these diesters were considered safe as used in cosmetic products.

Final Report on the Amended Safety Assessment of Diisopropyl Dimer Dilinoleate, Dicetearyl Dimer Dilinoleate, Diisostearyl Dimer Dilinoleate, Dioctyl Dimer Dilinoleate, Dioctyldodecyl Dimer Dilinoleate, and Ditridecyl Dimer Dilinoleate

Diisopropyl Dimer Dilinoleate, Dicetearyl Dimer Dilinoleate, Diisostearyl Dimer Dilinoleate, Dioctyl Dimer Dilinoleate, Dioctyldodecyl Dimer Dilinoleate, and Ditridecyl Dimer Dilinoleate are diesters of their respective alcohols and dilinoleic acid. They function as skin-conditioning agents in a variety of cosmetic products at concentrations around 10%, but may be used at concentrations up to 53% in lipsticks. These ingredients do not absorb radiation in the ultraviolet (UV) UVA or UVB range and the only impurities expected are &lt;0.5% dilinoleic acid, &lt;0.1% isopropyl alcohol or &lt;1% isostearyl alcohol, and/or small amounts of dilinoleic acid and cetearyl alcohol or octyldodecanol, depending on which diester is used. The potential skin penetration of these ingredients was evaluated using an estimate of the octanol/water partition coefficient (logP of 17.7) based on the structure of Diisopropyl Dimer Dilinoleate. This is consistent with the insolubility of these ingredients in water. Safety test data on dilinoleic acid (no adverse effects) were considered relevant because dilinoleic acid is a component of these diesters and a likely breakdown product. The acute oral and dermal LD50 values for rats of Diisopropyl, Diisostearyl, and Dioctyldodecyl Dimer Dilinoleate were &gt;5.0 g/kg. In a subchronic feeding study, macrophage aggregation was seen in the mesenteric lymph node at the lowest dose level (0.1% in the diet). These ingredients did not produce skin or ocular irritation in animal tests, nor were they comedogenic. Ames testing, clastogenesis in human lymphocytes in culture, and L5178Y mouse lymphoma cell forward mutations were all negative, indicating no dilinoleic acid genotoxicity. No carcinogenicity or reproductive/developmental toxicity data were available; however, structural alerts that would suggest a mutagenic or carcinogenic risk are absent. Significant reproductive/developmental toxicity or other systemic toxicity is not expected with these ingredients because they remain on the skin surface. In clinical studies, cosmetic formulations containing these ingredients did not produce skin irritation or sensitization, although one report of sensitization to dilinoleic acid appeared in the case literature. The Panel did note that the concentration of use of Diisopropyl Dimer Dilinoleate was reportedly as high as 53% in lipsticks, but that the highest concentration tested for irritation/sensitization is 27%. Given the size of these molecules, their relative insolubility in water, their lipophilic nature, and the absence of any significant case reports of allergic reactions, a use concentration of 53% is not likely to be associated with any adverse effects. Accordingly, these diesters were considered safe as used in cosmetic products.

Formation and Novel Thermomechanical Processing of Biocompatible Soft Materials

We demonstrated for the first time the thermo-mechanical processing of the organogels of dibutyllauroyl glutamide as a small molecule gelling agent (SMGA) in a biocompatible solvent, isostearyl alcohol. The study focused on the impact of novel thermomechanical processing parameters such as temperature, strain, and the cooling rate on the microstructure and macroscopic properties of gels. The properties of the gels were analyzed by dynamic light scattering and by rheological and electron microscopy methods. The modification of the thermoreversibility and viscoelastic properties of the gels can be associated with the changes in the micro-/nanofiber network structures. The micro-/nanofiber network structures are stable over a wide range of frequencies. Two temperature domains associated with distinct gelation behaviors and rheological properties were identified for the first time in the gelation of organic solvents using SMGA. The transition from one temperature domain to the next can be linked to the changes in the micro-/nanostructure.

Effect of foreign particles: a comprehensive understanding of 3D heterogeneous nucleation

A general kinetic model to describe both heterogeneous and homogeneous nucleation is put forward. Ranging from low to high supersaturations, heterogeneous nucleation plays a more relevant and comprehensive role in nucleation than expected, depending on the size and “contact angle” of foreign particles. It follows that genuine homogeneous nucleation may only be possible at very high supersaturations, and can become easier when convection is eliminated. The results have been verified by the nucleation experiments of N-lauroyl- l-glutamic acid di- n-butylamide from iso-stearyl alcohol solutions and microgravity experiments for CaCO 3 (calcite) nucleation.

Glyceryl monocaprylate/caprate as a moderate skin penetration enhancer

Eleven widely used lipophilic formulation excipients have been screened for their skin penetration enhancing effects. The excipients tested were glyceryl tricaprylate/caprate, isopropyl myristate, glyceryl monocaprylate/caprate, decyl oleate, polyethylene glycol-6 glyceryl dicaprylate/caprate, isopropyl isostearate, isostearyl isostearate, glyceryl monoisostearate, polyglyceryl-3 diisostearate, vegetable squalane and isostearyl alcohol. Excipient effects were evaluated by measuring skin permeability coefficients towards a model hydrophilic drug, 5-fluorouracil (5-FU), before and after a 6-h treatment with neat excipient. The skin penetration enhancing mixture, 10% (w/w) Azone® in propylene glycol, was used as a positive control. Only one excipient, glyceryl monocaprylate/caprate, had enhancement effects significantly above the buffer control ( p<0.05). This excipient increased 5-FU penetration 10-fold. log P octanol/water and hydrophilic–lipophilic balance values were calculated for each of the excipients. It was concluded that, of the excipients screened, glyceryl monocaprylate/caprate is the only penetration enhancer because (1) it is the least lipophilic, (2) it has surfactant properties, and (3) it has the optimum alkyl chain length for surfactant-type skin penetration enhancers. Since glyceryl monocaprylate/caprate has only moderate enhancement effects, it should be useful as a mild, well-tolerated skin penetration enhancer.

5 Final Report on the Safety Assessment of Cetearyl Alcohol, Cetyl Alcohol, Isostearyl Alcohol, Myristyl Alcohol, and Behenyl Alcohol

Cetearyl, Cetyl, Isostearyl, Myristyl, and Behenyl Alcohols are long-chain aliphatic alcohols that are, at most, only slightly toxic when administered orally at doses of 5 g/kg and greater. In acute dermal toxicity studies (rabbits), doses of up to 2.6 g/kg of Cetyl Alcohol and 2.0 g/kg of a product containing 0.8% Myristyl Alcohol were both practically nontoxic. Mild irritation was observed when a cream containing 3.0% Cetearyl Alcohol was applied to the skin of New Zealand albino rabbits. Cetyl Alcohol (50.0% in petrolatum) applied to abraded and intact skin of albino rabbits produced minimal to slight skin irritation. Cetyl Alcohol was considered to be practically nonirritating when instilled into the eyes of albino rabbits. An aerosol antiperspirant containing 3.0% Myristyl Alcohol induced mild to moderate irritation; a moisturizing lotion containing 0.8% Myristyl Alcohol was nonirritating to rabbit eyes. Corneal irritation was reported following an ocular test using a 5.0% Isostearyl Alcohol antiperspirant. Conjunctival irritation was observed 2 and 6 h after instillation of 1.0% Behenyl Alcohol. Isostearyl Alcohol (5.0% in propylene glycol) and an antiperspirant containing 5.0% Isostearyl Alcohol were not sensitizers in guinea pigs. Cetyl Alcohol was not mutagenic in Salmonella typhimurium LT2 mutant strains in the spot test. Clinical skin irritation and sensitization studies of product formulations containing up to 8.4% Cetyl Alcohol produced no evidence of irritation or sensitization. Moisturizing lotions containing 0.8% Myristyl Alcohol were nonirritating to human skin, and moisturizers containing 0.25% Myristyl Alcohol were neither irritants nor sensitizers. No signs of skin irritation or sensitization were observed in humans following the dermal application of 25% Isostearyl Alcohol. In a human skin sensitization study of a cream containing 3.0% Cetearyl Alcohol, none of the subjects had positive reactions. An analysis of the data and comparison with data from other toxicity studies on long-chain aliphatic alcohols is presented. Based on the available data included in this report, it is concluded that Cetearyl Alcohol, Cetyl Alcohol, Isostearyl Alcohol, Myristyl Alcohol, and Behenyl Alcohol are safe as cosmetic ingredients in the present practices of use.

1 Final Report on the Safety Assessment of Isostearyl Neopentanoate

Isostearyl Neopentanoate, the ester of Isostearyl Alcohol and Neopentanoic Acid, is used in cosmetic products as an emollient at concentrations up to 50 percent. The undiluted ingredient at doses up to 4 ml/kg was shown to be relatively non-toxic in short-and long-term feeding studies. Test data from animal and clinical studies indicate the undiluted ingredient is neither an irritant nor a sensitizer. A cosmetic formulation containing 16 percent Isostearyl Neopentanoate produced no phototoxicity and no photoallergenicity. Mutagenicity, carcinogenicity, and teratogenicity data were not available. Isostearyl Neopentanoate was not considered to be a significant comedogenic agent. On the basis of available data, it is concluded that this ingredient is safe as a cosmetic ingredient in its present practices of use.

Incidence of human skin sensitization to isostearyl alcohol in two separate groups of panelists.

Human repeated insult patch testing with an experimental pump spray antiperspirant formulation elicited sensitization reactions in two separate groups of panelists. After several rechallenges with variations of the formula components, isostearyl alcohol at 5% concentration in the product emerged as the causative agent in both groups. Due to the high content of alcohol in the pump spray antiperspirant, control patch testing was done with 100% ethanol, which served as the vehicle for testing isostearyl alcohol alone. All reactions were negative. Six out of 148 participants in the first group and one of 60 in the second group exhibited sensitization responses to isostearyl alcohol.

Fatty glycols and isostearyl alcohol as lipstick components

AbstractIt is now possible to formulate lipsticks with a minimum number of ingredients. By using isostearyl alcohol as the oil phase and the appropriate vicinal glycols as the wax phase, both of which are good bromo solvents, a wide range of plastic properties may be obtained. The necessity of using oxidation inhibitors and couplers for incompatible bromo solvents is avoided. These raw materials are colorless, nearly odorless and tasteless, nontoxic, nonirritating, oxidation‐stable, miscible with waxes, and are good emollients.