Hansen Solubility Parameters Values Research Articles

Tolterodine Tartrate Loaded Cationic Elastic Liposomes for Transdermal Delivery: In Vitro, Ex Vivo, and In Vivo Evaluations.

Tolterodine tartrate (TOTA) is a first-line therapy to treat overactive urinary bladder (OAB). Oral delivery causes high hepatic clearance, xerostomia, headache, constipation, and blurred vision. We addressed Hansen solubility parameter (HSP) and Design Expert oriented optimized cationic elastic liposomes for transdermal application. The experimental solubility was conducted in HSPiP predicted excipients to tailor formulations using surfactants, stearylamine, ethanol, and phosphatidylcholine (PC). These were evaluated for formulation characteristics. The optimized OTEL1 and OTEL1-G (gel) were compared against the drug solution (DS) and liposomes. In vitro and ex vivo studies were accomplished to investigate the insights into the mechanistic understanding of TOTA release and permeation ability. Finally, confocal laser scanning microscopy (CLSM) supported ex vivo results. HSP values of TOTA were closely related to tween-80, stearylamine, and human's skin. The size (153nm), %EE (87.6%), and PDI (0.25) values of OTEL1 were in good agreement to the predicted values (161nm, 80.4%, and 0.31) with high desirability (0.963). Spherical and smooth OTEL1 (including OTEL1-G and liposomes) vesicles followed non-Fickian drug release as compared to DS (Fickian) as evidence with n > 0.5 (Korsmeyer and Peppas coefficient). OTEL1 (containing lipid and surfactant as 90mg and 13.8mg, respectively) exhibited 2.6 and 1.8-folds higher permeation flux than DS and liposomes, respectively. Biocompatible cationic OTEL1 was safe and non-hemolytic. OTEL1 was promised as a lead vesicular approach and an alternative to conventional oral therapy to treat OAB in children and advanced age patients.

Predicting the binding affinity of chemicals to estrogen receptor using Hansen solubility parameters

Receptor-binding tests for the receptors of various substances are widely employed to identify drug candidates and predict the biological effects of chemical substances. Here, the results of chemicals binding to estrogen receptor (ER) reported in a validation study of the Organization for Economic Cooperation and Development TG 455 and the Hansen solubility parameter (HSP) values of the test substances were compared and examined using the Hansen sphere method, thus predicting potential HSPs that correspond to the ER-binding domain of agonists. Based on the results of the validation study and the HSP values of the test chemicals, a Hansen solubility sphere was created, and the ER potential parameter corresponding to the ER was obtained. The binding potential of the test substances to ER was predicted by comparing this potential parameter with the HSP of each test substance. These results indicate that ER binding properties can be predicted with high accuracy using the concept of HSP.

Are Hansen solubility parameters relevant in predicting the post-treatment effect on polyamide-based TFC membranes?

This study investigates the impact of solvent post-treatment on polyamide-based thin film composite (TFC) membranes, specifically examining the effect on commercial nanofiltration (NF) and reverse osmosis (RO) membranes. Na2SO4 rejection and increase in pure water permeance (PWP) were considered as the output parameters. The disparity in Hansen solubility parameters (HSP) between the post-treatment solution and the polyamide layer of the TFC membrane, denoted by Ra, is well adapted to understand the enhancement in water permeance through the membranes upon treatment. Aqueous solutions of dimethylformamide with a Ra value of 4, acetonitrile with a Ra value of 8.3, and ethanol with a Ra value of 12.7 were used as the post-treatment solutions. Our experimental design, based on the Box-Behnken design of Response Surface Methodology, incorporates variables such as the concentration of the solvent in the solution (% v/v), Ra value, and treatment time (s). Our findings demonstrate that the effect of post-treatment on the TFC membranes is not governed by the Ra value. Notably, while the post-treatment with the aqueous solution of acetonitrile, 80% v/v for 30 s, had considerable effects on NF membranes (124.5% enhancement in PWP; reduction of 3.5% in Na2SO4 rejection), its impact on RO membranes was negligible. Several factors explain this discrepancy, including the limitations of the HSP model for composite polymers, the inaccuracy of the PWP or salt rejection as a swelling indicator, variations in the HSP values of the polyamide layers for different membranes, and possible modifications in the interface between the support membrane and the polyamide layer. In summary, our study provides insights into the complex interactions between solvents and composite membranes, indicating that HSP alone is not a decisive factor in predicting post-treatment effects on polyamide-based TFC membranes.

A Procedure for Rational Probe Liquids Selection to Determine Hansen Solubility Parameters

AbstractHansen Solubility Parameters (HSP), viewed in the context of similarity whenever dispersion is focused, offer valuable insights into the surface characteristics of nanoparticles. However, existing methods for determining HSP via the sedimentation of nanoparticles require multiple probe liquids, resulting in time‐consuming, costly experiments with potential health risks. To address this, we developed a two‐step strategy that enables a systematic selection of liquids. The key element of the approach is to first identify the rough location of the Hansen sphere in the three‐dimensional Hansen space using a well‐chosen set of probe liquids of different polarities and chemical structures. Then, depending on the outcome of the first step, a particular choice of liquids is made for the final HSP determination. Taken together, the introduced procedure reduces the amount of required liquids for experiments from currently more than ten to a maximum of seven chosen based on a well‐defined, coherent methodology. Validation was performed on carbon black, non‐pigmentary nano‐scale titania, silicon/carbon composites, and lanthanum cobaltite particles, i. e., relevant materials that are commonly utilized in fuel cells, batteries, cyclohexene oxidation, catalytic combustion, photocatalysis, and heterogeneous Fenton reactions. The study showcases the potential to save time, costs, and efficiently determine HSP values in a comparable manner.

From Hansen solubility parameters to new anti-icing, viscoelastic sponges of terpolymer of tetrafluoroethylene, vinylidenefluoride, and hexafluoropropylene (THV)

THV, a relatively new hydrophobic polymer, has found wide application from explosives to sensors. Therefore, we decided to determine its Hansen Solubility Parameters (HSP) – one of the most important parameters in polymers processing. Studied 41 liquids can be divided into four groups: very good solvents (1), causing gelation (2) causing soaking or color change (3), and inert (4) and HSP values were calculated. We also proposed green chemistry solvents for THV. At the next stage, two solvents from group 1, and two from group 2, and their mixtures, were selected to determine the effect of a solvent on the THV sponge properties. The sponges were characterized by total pore volumes, porosity, mechanical properties, and surface morphology. Moreover, thermal, and anti-icing properties were studied for different film thicknesses. This holistic approach, together with a theoretical description of the icing process via a dynamic growth angle model, makes it possible to relate the sponge morphology to thermal, mechanical, hydrophobic, and anti-icing properties, showing that the studied sponges are strongly hydrophobic or superhydrophobic with a water contact angle (WCA) as large as 160° for THVAC. Considering anti-icing properties, total freezing time, delaying of recalescence, and possible ice removal by wind or vibration, the sponge obtained from the mixture of DMF and acetone (THVDMFAC) seems to be optimal. This sponge has the highest Young’s modulus, high thermal stability, and anti-freezing properties thus, it can be successfully applied in anti-icing covers in, for example, wind turbine blades.

HSPiP, Computational Modeling, and QbD-Assisted Optimized Method Validation of 5-Fluorouracil for Transdermal Products.

This study addressed the simplest and most efficient HPLC (high-performance liquid chromatography) method for the estimation of 5-fluorouracil (5-FU) from rat blood plasma by implementing the Hansen solubility parameters (HSP), computation prediction program, and QbD (quality by design) tool. The mobile phase selection was based on the HSP predictions and experimental data. The Taguchi model identified seven variables (preoptimization) to screen two factors (mobile phase ratio as A and column temperature as B) at three levels as input parameters in "CCD (central composite design)" optimization (retention time as Y1 and peak area as Y2). The stability study (freeze-thaw cycle and short- and long-term stability) was conducted in the rat plasma. Results showed that HSPiP-based HSP values and computational model-based predictions were well simulated with the experimental solubility data. Acetonitrile (ACN) was relatively suitable over methanol as evidenced by the experimental solubility value, HSP predicted parameters (δh of 5-FU - δh of ACN = 8.3-8.3 = 0 as high interactive solvent whereas δh of 5-FU - δh of methanol = 8.3-21.7 = -13.4), and instrumental conditions. CCD-based dependent variables (Y1 and Y2) exhibited the best fit of the model as evidenced by a high value of combined desirability (0.978). The most robust method was adopted at A = 96:4 and B = 40 °C to get earlier Y1 and high Y2 as evidenced by high desirability (D) = 0.978 (quadratic model with p < 0.0023). The estimated values of LLOD and LLOQ were found to be 0.11 and 0.36 μg/mL, respectively with an accuracy range of 94.4-98.7%. Thus, the adopted method was the most robust, reliable, and reproducible methodology for pharmacokinetic parameters after the transdermal application of formulations in the rat.

Development of multiferroic CFO:BTO core-shell nanocomposite inks for inkjet printing

Cobalt ferrite (CFO), barium titanate (BTO) core-shell nanoparticles (CFO:BTO NPs) exhibit multiferroic properties through the magnetoelectric effect. Inkjet printing is a direct-write, additive manufacturing technique for fabrication of electronic components and devices. Hansen Solubility Parameters (HSP) are a practical tool to understand solution and dispersion behavior of materials in a mixture. This work applies HSP analysis to improve CFO:BTO NPs synthesis and guide the ink formulation process. The estimated HSP values for CFO:BTO core-shell NPs (dD = 15.5, dP = 11.9, dH = 23, r = 4.6), CFO (dD = 15.9, dP = 10.6, dH = 22.5, r = 4.9), and BTO (dD = 16.6, dP = 9.7, dH = 15.4, r = 5.8) are analyzed. Limits and considerations of the HSP are discussed and results are combined with solvent thermal and fluid properties to develop ink formulations for multi-functional, multi-material inkjet printing applications.

Using NMR solvent relaxation to determine the Hansen solubility parameters of a carbon black and as a quick method to compare the surface quality of carbon blacks

The selection of appropriate solvents into which carbon blacks can be dispersed optimally is important for product manufacture and performance. Molecular-level interactions determine solvent suitability but are difficult to measure; existing experimental approaches require slow/expensive tests of dispersion stability. NMR solvent relaxation measurements are shown to be a fast indicator of solvent suitability, with sensitivity to the solvent-particle intermolecular forces making it a reliable proxy for determining optimum dispersibility. A structured approach to relaxation measurements with a selection of both good and poor solvents yields the Hansen solubility parameters (HSP) for the particle surface. Once obtained, suitable solvents (or solvent mixtures) can be selected from a database of HSP values to match the particle interface. The application of the NMR solvent relaxation approach for determining the HSP values is illustrated for a commercially available carbon black. Furthermore, individual solvent relaxation data for two solvents (e.g., hexane and IPA) with a variety of carbon blacks may be plotted against each other to highlight differences in surface chemistry. Using this approach, results are compared, for the first time, with data from inverse gas chromatography (IGC) with a relatively similar outcome. NMR solvent relaxation analysis provides a quick, facile, and cost-effective methodology to identify the replacement of both powder and solvent raw materials.Graphical

Prediction of acute oral toxicity using the Hansen solubility parameter

Acute oral toxicity is primarily determined using animal testing, as stated in the Organization for Economic Cooperation and Development (OECD) Test Guideline (TG) 420, 423, and 425. Currently, regarding animal welfare, few alternatives to animal testing such as in vitro approaches have been evaluated. Therefore, in this preliminary study examining a new method to determine acute oral toxicity, we investigated whether UN Globally Harmonized System all categories can be predicted using the Hansen solubility parameter (HSP). In particular, Hansen spheres were produced based on oral toxicity information of the test substances and their HSP values, and the respective parameters were identified. A comparison of these potential parameters with the HSP value of each test substance showed an accuracy of 84.1% (53/63), 10.0% (3/30) false negatives, and 21.2% (7/33) false positives. By comparing the HSP of the resulting potential parameters with a test substance, it is possible to predict acute oral toxicity with high accuracy.

Predictive Study of Eye Irritation Results Obtained from the STE Method Using Hansen Solubility Parameters

For animal protection, various studies on alternatives to safety tests in animals are being conducted. The short-time exposure (STE) method is described in the Organization for Economic Cooperation and Development Test Guideline 491 as an alternative to eye irritation animal testing. However, its accuracy and labor investment can be improved if the results can be predicted before the experiment. This study evaluated whether Hansen solubility parameter (HSP) values can be used to predict STE results. An HSP sphere was created based on the HSP values and STE results of 48 substances. Substances inside and outside the sphere were designated as dangerous and safe substances, respectively. The safety of each test substance was predicted by comparing the center point (R0) of the sphere with the relative energy difference, i.e., the ratio of each test substance (Ra). The accuracy, false-negativity, and false-positivity of the “irritant” and “non-irritant” designations, as determined by the STE results and Hansen sphere, were 91.7% (44/48), 4.8% (1/21), and 11.1% (3/27), respectively. These results indicate that HSP values can be used to predict STE results with high reproducibility, thereby evaluating the safety of the substances.

Extraction of Functional Components from Freeze-Dried Angelica furcijuga Leaves Using Supercritical Carbon Dioxide.

Angelica furcijuga (A. furcijuga), as a material for traditional Chinese medicine, has been widely used in Asian countries, such as China, Korea, and Japan, for several centuries owing to its therapeutic effects. In this study, A. furcijuga leaves were used as starting materials to extract functional substances using supercritical carbon dioxide (SC-CO2) at pressure and temperature ranges of 20–40 MPa and 40–80 °C, respectively. The extraction process was performed in a semibatch-type system with extraction times of 15–120 min. The high-performance liquid chromatography analysis indicated that kaempferol, ferulic acid, ligustilide, and butylidenephthalide as selected functional substances were successfully extracted under these operating conditions. An operating pressure of 30 MPa with an extraction time of 60 min seems to be an appropriate pressure to extract functional components from A. furcijuga leaves. The Hansen solubility parameter values and statistical analysis showed that SC-CO2 with 10% ethanol addition is a feasible tool to isolate these selected functional substances from the A. furcijuga matrix.

Designing Safer Solvents to Replace Methylene Chloride for Liquid Chromatography Applications Using Thin-Layer Chromatography as a Screening Tool

Methylene chloride, commonly known as dichloromethane (DCM), is a widely used chemical for chromatography separation within the polymer, chemical, and pharmaceutical industries. With the ability to effectively solvate heterocyclic compounds, and properties including a low boiling point, high density, and low cost, DCM has become the solvent of choice for many different applications. However, DCM has high neurotoxicity and is carcinogenic, with exposure linked to damage to the brain and the central nervous system, even at low exposure levels. This research focuses on sustainability and works towards finding safer alternative solvents to replace DCM in pharmaceutical manufacturing. The research was conducted with three active pharmaceutical ingredients (API) widely used in the pharmaceutical industry: acetaminophen, aspirin, and ibuprofen. Thin-layer chromatography (TLC) was used to investigate if an alternative solvent or solvent blend could show comparable separation performance to DCM. The use of the Hansen Solubility Parameter (HSP) theory and solubility testing allowed for the identification of potential alternative solvents or solvent blends to replace DCM. HSP values for the three APIs were experimentally determined and used to identify safer solvents and blends that could potentially replace DCM. Safer solvents or binary solvent blends were down-selected based on their dissolution power, safety, and price. The down-selected solvents (e.g., ethyl acetate) and solvent blends were further evaluated using three chemical hazard classification approaches to find the best fitting nonhazardous replacement to DCM. Several safer solvent blends (e.g., mixtures composed of methyl acetate and ethyl acetate) with adequate TLC performance were identified. Results from this study are expected to provide guidance for identifying and evaluating safer solvents to separate APIs using chromatography.

Design of Over-1000 nm Near-Infrared Fluorescent Polymeric Micellar Nanoparticles by Matching the Solubility Parameter of the Core Polymer and Dye.

Polymeric micellar nanoparticles (PNPs) encapsulating over-thousand-nanometer (OTN) near-infrared (NIR) fluorescent dye molecules in block polymers having hydrophobic and hydrophilic chains are promising agents for the dynamic imaging of deep tissue. To achieve OTN-NIR fluorescent PNPs (OTN-PNPs) having high brightness, it is crucial to increase the affinity between the core polymer and dye molecules by matching their polarities; thus, criteria and methods to evaluate the affinity are required. In this study, we used the Hansen solubility parameter (HSP), including the polarity term, to evaluate the affinity between the two substances. HSP values of the OTN-NIR fluorescent dye IR-1061 and four core polymers, poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), poly(ε-caprolactone) (PCL), and polystyrene (PSt), were calculated using the Hansen solubility sphere method and molecular group contribution method, respectively. The relative energy density between IR-1061 and each core polymer calculated using their HSP values revealed that the affinities of PLGA and PLA for IR-1061 are higher than those of PCL and PSt. Therefore, OTN-PNPs composed of PLGA, PLA, and PCL core polymers were prepared and compared. The OTN-PNPs having PLGA and PLA cores could be loaded with larger amounts of IR-1061, had higher photoluminescence intensities, and showed higher stability in phosphate buffered saline than those having PCL cores. Moreover, the OTN-PNPs having PLGA or PLA cores were used for the dynamic imaging of live mice. Thus, matching the solubility parameters of the core polymer and dye molecule is a useful approach for designing high-performance OTN-NIR fluorescent probes.

An alternative predictor of eye irritation that utilizes potential parameters of the human corneal epithelium model calculated based on Hansen solubility parameters

Eye irritation predictions are very important in the development of cosmetics and pharmaceuticals. For animal protection, alternative tests are being developed to replace the Draize test, which involves the use of rabbits to test eye irritation. The Vitrigel-eye irritancy test (Vitrigel-EIT), is one such alternative. As a preliminary study, we evaluated if Hansen solubility parameter (HSP) values can be used to predict Vitrigel-EIT results. An Hansen sphere was created based on the HSP values and Vitrigel-EIT results from 61 substances. Substances inside and outside of the sphere were designated as dangerous and safe substances, respectively. The safety of each test substance was predicted by comparing the center point (Ro) of the sphere with the relative energy difference, i.e., the ratio of each test substance (Ra). The accuracy, false negativity, and false positivity of the “irritant” and “nonirritant” designations, as determined by the Vitrigel-EIT results and Hansen sphere, were 91.8% (56/61), 2.3% (1/43), and 22.2% (4/18), respectively. These results indicated that HSP values can be used to predict Vitrigel-EIT results with high reproducibility, and thus are useful for evaluating the safety of substances.

Towards a framework for evaluating and reporting Hansen solubility parameters: applications to particle dispersions.

A thorough understanding of complex interactions within particulate systems is a key for knowledge-based formulations. Hansen solubility parameters (HSP) are widely used to assess the compatibility of the dispersed phase with the continuous phase. At present, the determination of HSP is often based on a liquid ranking list obtained by evaluating a pertinent dispersion parameter using only one pre-selected characterization method. Furthermore, one cannot rule out the possibility of subjective judgment especially for liquids for which it is difficult to decipher the compatibility or underlying interactions. As a result, the end value of HSP might be of little or no information. To overcome these issues, we introduce a generalized and technology-agnostic combinatorics-based procedure. We discuss the principles of the procedure and the implications of evaluating and reporting particle HSP values. We demonstrate the procedure by using SiNx particles synthesized in the gas phase. We leverage the analytical centrifugation data to evaluate stability trajectories of SiNx dispersions in various liquids to deduce particle-liquid compatibility.

Highly accurate predictor of eye irritation utilizing potential parameters of a reconstructed human cornea epithelium model calculated based on Hansen solubility parameters

Concerns regarding animal welfare have led to the need for alternatives to animal eye irritation tests. The reconstructed human cornea-like epithelium (RhCE) test is described in the OECD TG 492 as an alternative to animal eye irritation tests. However, the accuracy and labor investment of this method can be improved if the results can be predicted before the experiment. In this study, we evaluated whether Hansen solubility parameter (HSP) values can be used to predict the results of RhCE method using the LabCyte CORNEA-MODEL for 65 test substances. We found that HSP values can predict the RhCE method with high correlation (accuracy 84.6% (55/65), false-negative rate of 16.2% (7/43), and false-positive rate of 13.6% (3/22). These results indicate that HSP values can be used to predict the results RhCE method using LabCyte CORNEA-MODEL with high reproducibility, and thus are useful for evaluating the safety of substances.

Fast NMR relaxation, powder wettability and Hansen Solubility Parameter analyses applied to particle dispersibility

The selection of appropriate solvents into which inorganic and organic sub-micron particles can be dispersed is important for product manufacturability and performance. Molecular-level interactions determine solvent suitability but are difficult to measure; existing experimental approaches require slow/expensive tests of dispersion stability. Solvent relaxation NMR measurements are shown to be a fast indicator of solvent suitability, with sensitivity to the solvent-particle intermolecular forces making it a reliable proxy for stability measurements. A structured approach to relaxation measurements with a selection of both good and poor solvents yields the Hansen Solubility Parameters (HSP) for the particle surface. Suitable solvents can be selected from a database of HSP values, and solvents can be blended to match the particle interface. The application of the approach is illustrated using a range of surface modified zinc oxide and aluminum oxide particles, with similarities and differences between the particle surfaces becoming evident through the analysis.

Measurement of Hansen Solubility Parameters of Human Stratum Corneum.

Hansen Solubility Parameters (HSP) of human stratum corneum (SC) represent its polarity and are very important for design and optimization of dermatological formulations. However, there is no directly measured data available in the literature for such a crucial property, which is the subject of the present investigation. HSP of the SC was measured by solvent uptake here. 18 solvents/mixtures with different HSP values were selected and their uptake by the SC was measured at 32 °C. The solvents were then divided into good and bad solvents according to their uptake into the SC. The HSP discrete parts of “atomic dispersion forces (δD)”, “dipolar intermolecular forces (δP)”, and “hydrogen bonding (δH)” were then calculated using uptake data and HSPiP software. Results showed that δD, δP, and δH values of the SC at 32 °C are 16.5, 12, 7.7 respectively. The obtained HSP values, which were measured for the first time here, were then used to interpret enhancement effects of permeation enhancers and the uptake of vehicles by the SC using Relative Energy Difference (RED), with good correlations. SC HSP values can be further used in transdermal drug delivery, cosmetic formulations, safety issues, etc.

Evaluation of the influence of fine particle surface modification with the Hansen solubility parameters

Abstract In this study, we determined the Hansen solubility parameters (HSPs) of metal fine particles by experiments based on the Hansen solubility sphere method. A silane coupling treatment was applied to the metal fine particles to determine the HSPs from their dispersibilities. We examined changes in the HSP values after treatment by a silane coupling. We confirmed that the treatment with silane coupling agents, caused the HSPs of the particles to tend towards the HSPs of the surface treatment agent. We suggest that HSP theory is useful for selection of silane coupling agents.

Application of Multivariate Adaptive Regression Splines (MARSplines) for Predicting Hansen Solubility Parameters Based on 1D and 2D Molecular Descriptors Computed from SMILES String

A new method of Hansen solubility parameters (HSPs) prediction was developed by combining the multivariate adaptive regression splines (MARSplines) methodology with a simple multivariable regression involving 1D and 2D PaDEL molecular descriptors. In order to adopt the MARSplines approach to QSPR/QSAR problems, several optimization procedures were proposed and tested. The effectiveness of the obtained models was checked via standard QSPR/QSAR internal validation procedures provided by the QSARINS software and by predicting the solubility classification of polymers and drug-like solid solutes in collections of solvents. By utilizing information derived only from SMILES strings, the obtained models allow for computing all of the three Hansen solubility parameters including dispersion, polarization, and hydrogen bonding. Although several descriptors are required for proper parameters estimation, the proposed procedure is simple and straightforward and does not require a molecular geometry optimization. The obtained HSP values are highly correlated with experimental data, and their application for solving solubility problems leads to essentially the same quality as for the original parameters. Based on provided models, it is possible to characterize any solvent and liquid solute for which HSP data are unavailable.