Dimethyl Isosorbide Research Articles

Dimethyl Isosorbide and Its Mixtures with Aliphatic/Aromatic Hydrocarbons: Binary and Ternary Liquid–Liquid Equilibria and Thermodynamic Characterization

Dimethyl Isosorbide and Its Mixtures with Aliphatic/Aromatic Hydrocarbons: Binary and Ternary Liquid–Liquid Equilibria and Thermodynamic Characterization

Enhancing Sustainability in PLA Membrane Preparation through the Use of Biobased Solvents.

For the first time, ultrafiltration (UF) green membranes were prepared through a sustainable route by using PLA as a biopolymer and dihydrolevoclucosenone, whose trade name is Cyrene™ (Cyr), dimethyl isosorbide (DMI), and ethyl lactate (EL) as biobased solvents. The influence of physical-chemical properties of the solvent on the final membrane morphology and performance was evaluated. The variation of polymer concentration in the casting solution, as well as the presence of Pluronic® (Plu) as a pore former agent, were assessed as well. The obtained results highlighted that the final morphology of a membrane was strictly connected with the interplaying of thermodynamic factors as well as kinetic ones, primarily dope solution viscosity. The pore size of the resulting PLA membranes ranged from 0.02 to 0.09 μm. Membrane thickness and porosity varied in the range of 0.090-0.133 mm of 75-87%, respectively, and DMI led to the most porous membranes. The addition of Plu to the casting solution showed a beneficial effect on the membrane contact angle, allowing the formation of hydrophilic membranes (contact angle < 90°), and promoted the increase of pore size as well as the reduction of membrane crystallinity. PLA membranes were tested for pure water permeability (10-390 L/m2 h bar).

Development of a Versatile Lipid Core for Nanostructured Lipid Carriers (NLCs) Using Design of Experiments (DoE) and Raman Mapping.

The objective of this study was to develop a versatile lipid core for the 'brick-dust type of drugs' (poorly water-soluble and poorly lipid-soluble drugs). In the first step, excipients of different polarities were classified according to their behavior in aqueous solutions. Subsequently, binary mixtures were prepared with cetyl palmitate (Crodamol™ CP pharma, Campinas, São Paulo, Brazil) as the solid lipid, and its miscibility with other excipients was evaluated using Raman mapping and classical least squares (CLS). Based on the results, the excipients Crodamol™ CP pharma (hydrophobic), Super Refined™ DMI (dimethyl isosorbide; hydrophilic, Mill Hall, PA, USA), and Super Refined™ Lauryl Lactate (lauryl lactate, medium polarity, Mill Hall, PA, USA) were chosen to compose the lipid core. The ideal proportion of these excipients was determined using a mixture design and the standard deviation (STD) of image histograms as the response variables. After statistical evaluation of the DoE results, the final composition was determined, and drugs with different logP (0 to 10) and physicochemical characteristics were evaluated in the optimized mixture. The drugs butamben (Sigma-Aldrich Co., Spruce Street, St. Louis, MO, USA), tacrolimus (NutriFarm, São Paulo, Brazil), atorvastatin calcium, and resveratrol (Botica da Terra, Campinas, Brazil) presented a homogeneous distribution in the optimized lipid core, indicating that this is a promising system to be used in nanostructured lipid carrier (NLC) formulations of such types of drugs.

New Skin-Relevant Cell Coculture Model With Stratum Corneum-Like Layer.

Two-dimensional (2D) cell culture is an important tool in the discovery of skin-active agents. Fibroblasts and keratinocytes, more rarely fibroblast-keratinocyte cocultures, are usually used for that purpose, where test compounds are added by mixing with the overlaying growth medium. However, such an approach is suboptimal because it lacks the stratum corneum component. The stratum corneum acts as a selective gatekeeper and opposes the intradermal permeation of many compounds that are bioactive when placed in direct contact with cells. One solution is to use reconstituted epidermis, but this approach is costly and time consuming. Here, a model is proposed, where the simplicity and convenience of the 2D cell culture is combined with the advantage of a hydrophobic barrier reminiscent of the skin horny layer. This model was tested with skin-relevant solvents, as well as with "naked" hydrophilic and encapsulated compounds. Cell viability and collagen stimulation were used as readouts. The results showed that the incorporation of a stratum corneum-substitute barrier on top of a 2D cell culture reduced the cytotoxicity of a common cosmetic solvent, dimethyl isosorbide (DMI), in cell culture and modified the bioactivity of the added actives (magnesium ascorbyl phosphate [MAP] and oligomeric proanthocyanidins [OPCs]/levan biopolymer), which became dependent on their ability to penetrate through a lipidic layer. Taken together, these results indicate a better physiological relevance of this cell culture model in workflows aimed at the discovery and analysis of skin-active compounds than conventional 2D systems.

Eco-friendly synthesis of high-performance polyimide materials using bio-based greener solvents: Towards sustainable technologies in space environment

Polyimide-based materials offer high thermal stability, mechanical strength, and resistance to UV and solar radiation, making them ideal candidates for use in demanding space missions. In particular, polyimide membranes find practical application in large deployable and inflatable structures, as well as in solar propulsion sails for deep space missions. In this work, thermally stable polyimides with fully aromatic structure and trifluoromethyl functional groups were synthesized by a two-step method using bio-based alternative solvents, namely dimethyl isosorbide (DMI) and dihydrolevoglucosenone (Cyrene). These solvents are considered environmentally friendly and greener alternatives compared to conventional dipolar aprotic solvents like dimethylacetamide (DMAc). Using the in-house-made aromatic polyimides, membranes were fabricated and their properties were compared to those made of PI synthesized using conventional routes in DMAc. Different routes for solvent removal were investigated during membrane fabrication. Several key characteristics were considered to assess the effect of using greener solvents on the final properties of the polyimide materials, including hydrophobicity degree from water contact angle (WCA), thermal behavior from differential scanning calorimetry (DSC), and viscoelastic properties from dynamic-mechanical analysis (DMA). These analyses provide insights into the thermal and mechanical response of the PI materials under varying temperatures and loads, which is essential for designing structures that can withstand the harsh conditions of space, such as in solar sail propulsion systems.

Furandicarboxylate Polyesters: A Comprehensive ADMET Study of a Novel Class of Furan-Based α,ω-Diene Monomers.

The present research article delves into the preparation of a new class of bio-based polyesters from α,ω-diene furandicarboxylate monomers. In particular, it exploits the use of acyclic diene metathesis polymerisation (ADMET) on 2,5-furandicarboxylic acid (FDCA)-derived compounds. First, a library of furan-based α,ω-diene monomers was prepared via acid- or base-catalyzed transesterification of 2,5-furandicarboxylic acid dimethyl ester (FDME) with commercially available alcohols incorporating terminal olefins, i. e., allyl alcohol, but-3-en-1-ol, hex-5-en-1-ol and dec-9-en-1-ol. Then, the novel monomers were subjected to ADMET polymerisation employing different catalysts and reaction conditions. Interestingly, first-generation Grubbs catalyst was found to be the best promoter for ADMET polymerisation. This catalyst allowed the preparation of a new family of bio-based polyesters with molecular weights up to 26.4 kDa, with good thermal stability, and adaptable cis-trans conformations. Results also revealed that the monomer structure had a direct impact on the polymerisation efficiency and the resulting thermal properties. The effect of green bio-based solvents such as Cyrene™, dimethyl isosorbide (DMI) and γ-valerolactone (GVL) on the polymerisation process was also studied. Data collected showed that the solvent concentration influenced both the yield and length of polymers formed. Furthermore, some co-polymerisation experiments were conducted; the successful integration of different monomers in the resulting copolymer was shown to affect the glass transition temperature (Tg) of the resulting materials.

UV–VIS-NIR optical properties of micrometric-thick polyimide membranes for lightweight devices in space

The optical properties of micrometric-thick polyimide membranes were analyzed between 200 nm and 2500 nm to assess their potential use as substrates for the fabrication of wide optical devices for space applications. These membranes were prepared from fully aromatic polyimides containing trifluoromethyl functional groups which have already been used in space and have shown excellent resistance to the space environment. Various membranes have been synthesized using two different solvents and thermal treatments. Spectrophotometric and ellipsometric measurements were performed to estimate the spectral refractive index (n) and extinction coefficient (k) of various membranes synthesized using a standard solvent, such as N,N-dimethylacetamide (DMAc) and an alternative bio-based solvent, that is dimethyl isosorbide (DMI). The investigation has been extended to consider the morphological properties of the surface and the consequences they have on the diffusion of incident light. This work demonstrates that it is possible to use a green and non-hazardous solvent for the synthesis of thin polyimide membranes, even in the perspective of a large-scale manufacturing process that is greener and more sustainable. Using similar synthesis methods, the surface topography of the polyimide obtained with DMI is found to be smoother. Results suggest that membranes obtained by this bio-based solvent can also be used for optical devices where the scattered component of reflected and transmitted radiation needs to be minimized.

Novel Prospects of Non-aqueous Solvents for Designing Injectables Parenteral Formulation

The most efficient method for delivering pharmaceutically active compounds with a limited therapeutic index and low bioavailability is via parenteral administration. Depending on the patient's location and the type of ailment being treated, injectable medication products are quite different and specialized. Water-insoluble medications have long been dissolved using non-aqueous solvents in subcutaneous or intramuscular pharmaceutical formulations. The necessity for these transporters has grown recently as a result of the drug discovery process' production of numerous medicines with poor water solubility. The formulator uses nonaqueous solvents to create stable, practical parenteral dosage forms. The drawbacks of suspensions, such as non-uniform dosing caking and the potential sluggish release of the medication when it is not wanted, are avoided by using a parenteral solution. These organic solvents, which are thought to be inert chemically and physiologically, could have toxicological and pharmacological consequences. Therefore, prior to their administration, especially when given undiluted, it is crucial to understand the tolerance and activity of nonaqueous solvents. Propylene glycol, polyethylene glycols, and ethanol are examples of well-researched organic solvents. Other solvents include those described for specific applications (dimethyl sulfoxide, N-methyl-2-pyrrolidone, glycofurol, Solketal, glycerol formal, acetone), those not reported for intravascular applications but potentially useful (tetrahydrofurfuryl alcohol, diglyme, dimethyl isosorbide, e In addition to some specialized and infrequently used nonaqueous solvents, this overview discusses their toxicity, chemical and physical characteristics, and applications in parenteral formulations.

Skin penetration of caffeine from commercial eye creams and eye creams designed and optimized based on Hansen solubility parameters

Computer-aided formulation design can streamline and speed up product development. In this study, ingredient screening and optimizing software, Formulating for Efficacy® (FFE), was used to design and optimize creams for the topical delivery of caffeine. FFE was set up to optimize lipophilic active ingredients, therefore, this study challenged the program’s capabilities. The effect of two chemical penetration enhancers, including dimethyl isosorbide (DMI) and ethoxydiglycol (EDG), were studied based on their favorable Hansen Solubility Parameter physicochemical input parameters for the skin delivery of caffeine in the FFE® software application. Four oil-in-water emulsions containing 2% caffeine were formulated, one without a chemical penetration enhancer, one with five percent of DMI, one with five percent of EDG, and one with 2.5% of DMI and EDG each (DMI + EDG). Additionally, three commercial products were used as reference products. The cumulative amount of caffeine released and permeated, and the flux across Strat-M® membranes were determined using Franz diffusion cells. The eye creams had skin-compatible pH, excellent spreadability for the application area, were opaque emulsions with 14–17 μm droplet size, and were stable at 25 °C for 6 months. All four eye creams formulated released over 85% of caffeine in 24 h, outperforming the commercial products. DMI + EDG cream provided the highest permeation in vitro in 24 h, which was significantly higher than the commercial products (p < 0.05). FFE proved to be a valuable and quick tool to aid in the topical delivery of caffeine.

Characterization of piroctone olamine for topical delivery to the skin.

Dandruff and its more severe related condition, seborrheic dermatitis affects a high proportion of the population at some point in their life. Piroctone olamine, also known as Octopirox® (OPX) is the monoethanolamine salt of piroctone and is an antifungal agent widely used for the management of dandruff. The aim of the present work was to characterize the physicochemical properties of piroctone olamine and to conduct pre-formulation studies for the development of novel topical formulations of this active. An HPLC method was developed and validated for the analysis of OPX. The melting point was determined using the DSC Q2000 (TA Instruments, USA). The distribution coefficient (logD(O/PBS) ) and partition coefficient (log Po/w ) was determined in phosphate-buffered saline (PBS) AND deionized (DI) water using the shake flask method. All experiments were performed at room temperature. The solubility was determined experimentally by adding amount of active to a solvent. The samples were kept at 32° ± 1°C for 48 h in a water bath. The stability of the compound was determined in a range of solvents by preparing solutions of 1mg mL-1 in the relevant solvents. These solutions were kept and stirred throughout the experiment at 32 ± 1°C, and aliquots were taken at 24, 48 and 96 h. The HPLC method was developed successfully; however, samples at the lower end of the calibration curve showed lower degrees of precision and accuracy. Based on experiments with DSC, the melting point was observed at an onset temperature of 132.4°C. The LogD was determined to be 1.84. The compound had the highest solubility in methanol (278.4mg mL-1 ) and propylene glycol (PG), with a value of 248.8mg mL-1 . The lowest solubility for OPX was in dimethyl isosorbide (9.9mg mL-1 ), Labrafac™ (3.6mg mL-1 ) and isostearyl isostearate (0.5mg mL-1 ). Over the 4 days, OPX showed stability in ethanol and PG, while a notable decrease in OPX was observed in PBS and DI water at 32 ± 1°C. The physicochemical properties of OPX were characterized to find suitable excipients able to target the epidermis for topical delivery. Building on these findings, future work will focus on the development of novel topical formulation of OPX.

Biobased dimethyl isosorbide as an efficient solvent for alkaline hydrolysis of waste polyethylene terephthalate to terephthalic acid

Biobased DMI showed good ability to rapidly dissolve PET with a solubility of 0.3 gPET gDMI−1 at 170 °C in 10 min and DMI-based solvents were highly effective for alkaline hydrolysis of PET to generate TPA with a yield of 99.6% at 100 °C in 30 min.

Enabling efficient dissolution and fractionation of lignin by renewable and adjustable dimethyl isosorbide-based solvent systems

Efficient dissolution is highly important for upgrading of lignin into useful chemicals, which relays on the development of robust solvent systems. Herein, a novel, green, and robust solvent system for lignin dissolution was developed using biomass-derived dimethyl isosorbide (DMI) and water. Interestingly, the developed DMI-based solvent systems showed good ability to dissolve different types of lignin, i.e., alkali lignin (AL), enzymatic hydrolysis lignin (EHL), kraft lignin (KL) and dealkaline lignin (DAL), by tuning the weight ratio of DMI and water. Systematic investigations revealed that the lignin solubility correlated with Hansen solubility parameters and Kamlet-Taft parameters although the relationship varied with the lignin type. More importantly, lignin (with AL as an example) fractions with controlled molar mass could be obtained via gradient precipitation by gradually increasing the water content in the solvent system. Additionally, DMI had a good recyclability, and the recycled DMI showed no obvious decrease in the ability to dissolve lignin. This work provided an innovative and green solvent system to dissolve lignin, contributing to the realization of a “closed-loop” biorefinery process.

Lignin Nanoparticles as Sustainable Photoprotective Carriers for Sunscreen Filters.

Sunscreen filters may be degraded after prolonged UV exposure with loss of their shielding property and generation of harmful radical species. They are contained in cosmetic formulations in high concentrations, so the improvement of photostability is of relevance for safety concerns. We report here that lignin nanoparticles are sustainable carriers and photostabilizers of two common UV chemical filters, namely, avobenzone and octyl methoxycinnamate. These compounds have been encapsulated by nanoprecipitation into kraft lignin nanoparticles using eco-certified dimethyl isosorbide as a primary solvent and deionized water as an antisolvent. After the encapsulation, both compounds significantly prolonged the half-life stability against UV irradiation. The stabilizing properties of lignin nanoparticles were further improved by coencapsulation of avobenzone and octyl methoxycinnamate with hydroxytyrosol, a natural phenol with antioxidant activity recovered from olive oil wastes and characterized by skin regenerative properties.

Acid catalyzed synthesis of dimethyl isosorbide via dimethyl carbonate chemistry

Dimethyl isosorbide (DMI) is a bio-based solvent that can be used as green alternative for conventional dipolar media (dimethyl sulfoxide, dimethylformamide, and dimethylacetamide). The main synthetic procedures to DMI reported in the literature are based on the methylation of isosorbide employing different alkylating agents including toxic halogen compounds such as alkyl halides. A more sustainable alternative would be to employ dimethyl carbonate (DMC), a well-known green reagent and solvent, considered one of the most promising methylating agents for its good biodegradability and low toxicity. Indeed, in recent years, DMC-promoted methylation of isosorbide has been extensively exploited although mostly in the presence of a base or an amphoteric catalyst. In this work, we report for the first time a comprehensive investigation on the synthesis of DMI via DMC chemistry promoted by heterogeneous acid catalyst (Amberlyst-36 and Purolite CT275DR). Reaction conditions were optimized and then applied for the methylation of isosorbide and its epimers, isoidide and isomannide. Considerations on the related reaction mechanism were reported highlighting the difference in the preferred reaction pathways among this new synthetic approach and the previously reported base-catalyzed procedures.

Efficient pretreatment using dimethyl isosorbide as a biobased solvent for potential complete biomass valorization

Efficient pretreatment under mild conditions (120 °C, 60 min) using biobased dimethyl isosorbide for potential complete biomass valorization.

Nickel-Catalyzed Reductive Cross-Coupling of Aryl Bromides with Vinyl Acetate in Dimethyl Isosorbide as a Sustainable Solvent.

A nickel-catalyzed reductive cross-coupling has been achieved using (hetero)aryl bromides and vinyl acetate as the coupling partners. This mild, applicable method provides a reliable access to a variety of vinyl arenes, heteroarenes, and benzoheterocycles, which should expand the chemical space of precursors to fine chemicals and polymers. Importantly, a sustainable solvent, dimethyl isosorbide, is used, making this protocol more attractive from the point of view of green chemistry.

Olive leaf-derived PPAR agonist complex induces collagen IV synthesis in human skin models.

IntroductionPeroxisome proliferator‐activated receptor (PPAR) agonists are known to modulate the synthesis of dermal lipids and proteins including collagens. Olive (Olea europaea) leaves have been reported to contain PPAR‐binding ligands. Collagen IV, a major dermal‐epidermal junction (DEJ) protein, degrades with both age and disease. Here, we report the formulation of a novel multi‐ligand complex, Linefade, and its effects on collagen IV synthesis.MethodsLinefade prepared from the leaves of Olea europaea contains 2% w/w plant extract solids dissolved in a mixture of glyceryl monoricinoleate and dimethyl isosorbide. In silico docking was performed with PPAR‐α (PDB ID: 2P54). Linefade was evaluated for PPAR‐α‐dependent transcription in a luciferase reporter assay system. Cell viability and collagen IV levels in human dermal fibroblast cultures were measured using the MTT method and ELISA assay, respectively. Transcriptome analysis was conducted on a full‐thickness reconstituted human skin (EpiDermFT) model. Ex vivo cell viability and collagen IV immunostaining were performed on human skin explants.ResultsIn silico docking model of the major constituents (oleanolic acid and glyceryl monoricinoleate) produced a co‐binding affinity of −6.7 Kcal/mole. Linefade significantly increased PPAR‐α transcriptional activity in CHO cells and collagen IV synthesis in adult human dermal fibroblasts. Transcriptome analysis revealed that 1% Linefade modulated the expression of 280 genes with some related to epidermal differentiation, DEJ, PPAR, Nrf2 and retinoid pathways. An ex vivo human explant study showed that 1% Linefade, delivered via a triglycerides excipient, increased collagen IV levels along the dermal–epidermal junction by 52%.ConclusionIn silico modelling and in vitro and ex vivo analyses confirmed Linefade‐mediated activation of PPAR‐α and stimulation of collagen IV synthesis.

Development of Aqueous Formulation Containing the Extracted Mangiferin

Mangiferin, a polyphenol of C-glycosylxanthone, exhibits various bioactivities with poor aqueous solubility. It is known as a potent antioxidant, which leads to remarkable UV protection and anti-aging properties. Mangiferin can be found in many plant species, among which the mango leaf is one of the primary sources. From our study, the extraction yield of mangifein obtained from the leaves of Mangifera indica L. variety Nam Doc Mai was 3.17% with 95.02% ± 0.064 purity (HPTLC analysis). The solubility of mangiferin in the studied pure solvents arranging in descending order were ethoxydiglycol, dimethyl isosorbide, polyethylene glycol 400, polyethylene glycol 600, propylene glycol, dipropylene glycol, glycerin, isopentyldiol, methanol, ethanol and water, whereas the addition of the solvent in water could increase the aqueous solubility of mangiferin. In several cases, the solubility was apparently higher than that dissolved in its pure solvent state. The log-linear solubility model for the cosolvent system was used to calculate the volume fractions of the selected solvents needed to solubilize mangiferin content at the twenty times of the IC50 against DPPH radicals. In conclusion, the developed aqueous formulation contained 0.5% w/v of mangiferin and 20% w/v of polyethylene glycol 600 or dipropylene glycol as a solubilizer in water.

Dermal Delivery of Niacinamide-In Vivo Studies.

In vivo human studies are considered to be the “gold standard” when investigating (trans)dermal delivery of actives. Previously, we reported the effects of a range of vehicles on the delivery of niacinamide (NIA) using conventional Franz cell studies. In the present work, dermal delivery of NIA was investigated in vivo in human subjects using confocal Raman spectroscopy (CRS) and tape stripping (TS). The vehicles investigated included propylene glycol (PG), Transcutol® P (TC), binary combinations of PG with oleic acid (OA) or linolenic acid (LA) and a ternary system comprising of TC, caprylic/capric triglyceride (CCT) and dimethyl isosorbide (DMI). For the CRS studies, higher area under curve (AUC) values for NIA were observed for the PG:LA binary system compared with PG, TC and TC:CCT:DMI (p < 0.05). A very good correlation was found between the in vitro cumulative permeation of NIA and the AUC values from Raman intensity depth profiles, with a Pearson correlation coefficient (R2) of 0.84. In addition, an excellent correlation (R2 = 0.97) was evident for the signal of the solvent PG and the active. CRS was also shown to discriminate between NIA in solution versus crystalline NIA. The findings confirm that CRS is emerging as a powerful approach for dermatopharmacokinetic studies of both actives and excipients in human.

Dimethyl isosorbide via organocatalyst N-methyl pyrrolidine: scaling up, purification and concurrent reaction pathways

High-yielding methylation of isosorbide via DMC chemistry promoted by N-methyl pyrrolidine is herein reported. This study addresses: DMI purification, scale-up tests, insights on the catalyst role and on the reaction pathways leading to DMI.