Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Influence of high pressure compaction on solubility and intrinsic dissolution of ibuprofen binary mixtures employing standard excipients.

ABSTRACT: Enabling formulations often depend on functional excipients. However, the question remains whether excipients regarded as standard establish similar interactions and subsequently improvement of solubility when employed at unusual manufacturing process conditions. In this study, compaction of API under high pressure in the presence of hydrophilic excipients is proposed as a technique to improve the solubility and/or dissolution rate with an acceptable preservation of the supersaturation state. Binary mixtures of ibuprofen (IBU) with hydroxypropyl cellulose, isomalt, mannitol and sorbitol were compacted applying high pressure (500 MPa) with and without a previous co-milling step. Intrinsic dissolution rate (IDR) was selected to characterize and evaluate dissolution performance. The IDR of neat IBU increased from 5 to 88 fold and the aqueous solubility in the range of 3 to 54%. Regarding the polyols isomalt showed the highest impact on solubility and dissolution, without changing the crystallinity of IBU independent of a co-milling step. Even higher impact was achieved in combination with HPC. However, only without a previous co-milling step, ibuprofen remained crystalline, while co-milling induced an amorphous IBU-content of 38%. Based on XRPD and DSC findings, higher IDR and solubility values correlated with crystal modifications as well as IBU/excipient interactions.

SUBMITTER: Ibraheem B

PROVIDER: S-EPMC8022821 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Immediate-Release Nifedipine Binary Dry Powder Mixtures with Nanocellulose Featuring Enhanced Solubility and Dissolution Rate.

Project description:Nifedipine (NIF) is a 1,4-dihydropyridine-based calcium channel blocker with poor solubility, whose bioavailability is highly dependent on the type of formulation. Dry powder mixtures of 20% w/w NIF with microcrystalline cellulose (MCC) and its high surface area nanocellulose analogue, which is namely Cladophora (CLAD) cellulose, were produced by heating at the melting temperature of the drug for 1 h. Non-heated samples were used as a reference. The solid-state properties of the mixtures were characterized by scanning electron microscopy, differential scanning calorimetry and X-ray diffraction. The drug release was studied in biorelevant media, including simulated gastric fluid (SGF), fasted-state simulated intestinal fluid (FaSIF) and fed-state simulated intestinal fluid (FeSIF). An enhanced apparent solubility and faster dissolution rate of NIF were observed in the heated mixture of NIF with CLAD-H in all tested biorelevant media (i.e., SGF, FaSIF and FeSIF), which was due to NIF amorphization in the high surface area nanocellulose powder. Ordinary MCC, which is essentially non-porous, did not produce an enhancement of a similar magnitude. The results of the study suggest that dry powder formulation using high surface area nanocellulose is a facile new strategy for formulating calcium channel blocker drugs, which could potentially be a viable alternative to currently used soft gel liquid capsules.

| S-EPMC6359467 | biostudies-literature

Solubility of Organosolv Lignin in γ-Valerolactone/Water Binary Mixtures.

Project description:The solubility of lignin in a mixture of γ-valerolactone (GVL) and water at different weight ratios was measured using the Hildebrand solubility parameters. Based on the molecular structure of lignin, its solubility parameter (δ-value) was calculated as 25.5 MPa1/2 . The δ-value for aqueous GVL solvent increased from 23.1 MPa1/2 for pure GVL to 45.6 MPa1/2 for pure water. Therefore, the lignin solubility was predicted to increase with increasing GVL concentration in the aqueous mixture up to approximately 92-96 wt % of GVL. A ternary diagram describing the phase behavior of water-GVL-lignin mixtures at room temperature was constructed based on the experimental results. The three-component system exhibited a complex behavior with a liquid-liquid and solid-liquid-liquid phase split. The efficiency of the selected fractionation trials in a previous work was validated using the ternary solubility diagram. A promising recovery pathway and lignin isolation method were deduced from the results of this work.

| S-EPMC6586022 | biostudies-literature

Solubility Determination and Correlation of Warfarin Sodium 2?Propanol Solvate in Pure, Binary, and Ternary Solvent Mixtures.

Project description:The solubility of warfarin sodium isopropanol solvate (WS·IPA), a widely used anticoagulant, was determined at temperatures ranging from 278.15 to 333.15 K in four pure solvents (acetone, ethanol, IPA, and water), five binary solvent mixtures (IPA + acetone, IPA + ethanol, IPA + water, IPA + heptane, and IPA + hexane), and five ternary solvent mixtures (IPA + acetone + heptane, IPA + acetone + hexane, IPA + ethanol + heptane, IPA + ethanol + hexane, and IPA + water + heptane) using the polythermal method. It was demonstrated that the solubility of WS·IPA increases with increasing temperature in the pure solvents and at constant solvent composition in the solvent mixtures. In addition, the solubility of WS·IPA in IPA increases with increasing content of acetone, ethanol, and water, which act as cosolvents, and decreases with increasing content of heptane and hexane, which act as antisolvents. The experimental solubility data of WS·IPA in pure solvents and binary and ternary solvent mixtures were correlated using the modified Apelblat and ?h model equations. The correlated solubility data agree with the experimental data based on the relative deviation and the average relative deviation (ARD %) values. Thus, the correlated and experimentally derived solubility data of WS·IPA provide a pathway to engineer advanced pharmaceutical crystallization processes for WS·IPA.

| S-EPMC7291792 | biostudies-literature

Exploring the Solubility Limits of Edaravone in Neat Solvents and Binary Mixtures: Experimental and Machine Learning Study.

Project description:This study explores the edaravone solubility space encompassing both neat and binary dissolution media. Efforts were made to reveal the inherent concentration limits of common pure and mixed solvents. For this purpose, the published solubility data of the title drug were scrupulously inspected and cured, which made the dataset consistent and coherent. However, the lack of some important types of solvents in the collection called for an extension of the available pool of edaravone solubility data. Hence, new measurements were performed to collect edaravone solubility values in polar non-protic and diprotic media. Such an extended set of data was used in the machine learning process for tuning the parameters of regressor models and formulating the ensemble for predicting new data. In both phases, namely the model training and ensemble formulation, close attention was paid not only to minimizing the deviation of computed values from the experimental ones but also to ensuring high predictive power and accurate solubility computations for new systems. Furthermore, the environmental friendliness characteristics determined based on the common green solvent selection criteria, were included in the analysis. Our applied protocol led to the conclusion that the solubility space defined by ordinary solvents is limited, and it is unlikely to find solvents that are better suited for edaravone dissolution than those described in this manuscript. The theoretical framework presented in this study provides a precise guideline for conducting experiments, as well as saving time and resources in the pursuit of new findings.

| S-EPMC10574143 | biostudies-literature

Controlled Suspensions Enable Rapid Determinations of Intrinsic Dissolution Rate and Apparent Solubility of Poorly Water-Soluble Compounds.

Project description:To develop a small-scale set-up to rapidly and accurately determine the intrinsic dissolution rate (IDR) and apparent solubility of poorly water-soluble compounds.The IDR and apparent solubility (Sapp) were measured in fasted state simulated intestinal fluid (FaSSIF) for six model compounds using wet-milled controlled suspensions (1.0% (w/w) PVP and 0.2% (w/w) SDS) and the μDISS Profiler. Particle size distribution was measured using a Zetasizer and the total surface area was calculated making use of the density of the compound. Powder and disc dissolution were performed and compared to the IDR of the controlled suspensions.The IDR values obtained from the controlled suspensions were in excellent agreement with IDR from disc measurements. The method used low amount of compound (μg-scale) and the experiments were completed within a few minutes. The IDR values ranged from 0.2-70.6 μg/min/cm2 and the IDR/Sapp ratio ranged from 0.015 to 0.23. This ratio was used to indicate particle size sensitivity on intestinal concentrations reached for poorly water-soluble compounds.The established method is a new, desirable tool that provides the means for rapid and highly accurate measurements of the IDR and apparent solubility in biorelevant dissolution media. The IDR/Sapp is proposed as a measure of particle size sensitivity when significant solubilization may occur.

| S-EPMC5533823 | biostudies-other

Binary Mixtures of Some Active Pharmaceutical Ingredients with Fatty Alcohols-The Criteria of Successful Eutectic Formation and Dissolution Improvement.

Project description:Pharmaceutical eutectics are solid mixtures, where the crystals of active pharmaceutical ingredients (APIs) are finely divided in the phase-separated microstructures. The size reduction makes the eutectic formation a viable option to improve the dissolution rate of the poorly soluble APIs. In the present study, ibuprofen, naproxen, and sorafenib were investigated in terms of their phase behaviors with fatty alcohols, such as tetradecanol, octadecanol, and docosanol. Among the studied APIs, only ibuprofen was able to form eutectics with the fatty alcohols, and this was in agreement with the feasibility prediction based on the van 't Hoff equation and solubility parameters. In vitro release behavior was significantly improved for the ibuprofen/octadecanol eutectic mixture, although the practical insolubility of octadecanol in water was the opposite of the outstanding hydrophilicity of usual eutectic formers. The feasibility prediction and the choice of eutectic formers in the present study will be useful in advancing the utility of the pharmaceutical eutectics.

| S-EPMC7698041 | biostudies-literature

Solubility of Sulfamethazine in the Binary Mixture of Acetonitrile + Methanol from 278.15 to 318.15 K: Measurement, Dissolution Thermodynamics, Preferential Solvation, and Correlation.

Project description:Solubility of sulfamethazine (SMT) in acetonitrile (MeCN) + methanol (MeOH) cosolvents was determined at nine temperatures between 278.15 and 318.15 K. From the solubility data expressed in molar fraction, the thermodynamic functions of solution, transfer and mixing were calculated using the Gibbs and van 't Hoff equations; on the other hand, the solubility data were modeled according to the Wilson models and NRTL. The solubility of SMT is thermo-dependent and is influenced by the solubility parameter of the cosolvent mixtures. In this case, the maximum solubility was achieved in the cosolvent mixture w0.40 at 318.15 K and the minimum in pure MeOH at 278.15 K. According to the thermodynamic functions, the SMT solution process is endothermic in addition to being favored by the entropic factor, and as for the preferential solvation parameter, SMT tends to be preferentially solvated by MeOH in all cosolvent systems; however, δx3,1<0.01, so the results are not conclusive. Finally, according to mean relative deviations (MRD%), the two models could be very useful tools for calculating the solubility of SMT in cosolvent mixtures and temperatures different from those reported in this research.

| S-EPMC8706450 | biostudies-literature

Dissolution of Silk Fibroin in Mixtures of Ionic Liquids and Dimethyl Sulfoxide: On the Relative Importance of Temperature and Binary Solvent Composition.

Project description:We studied the dependence of dissolution of silk fibroin (SF) in mixtures of DMSO with ionic liquids (ILs) on the temperature (T = 40 to 80 °C) and DMSO mole fraction (χDMSO = 0.5 to 0.9). The ILs included BuMeImAcO, C3OMeImAcO, AlBzMe2NAcO, and Bu4NAcO; see the names and structures below. We used design of experiments (DOE) to determine the dependence of mass fraction of dissolved SF (SF-m%) on T and χDMSO. We successfully employed a second-order polynomial to fit the biopolymer dissolution data. The resulting regression coefficients showed that the dissolution of SF in BuMeImAcO-DMSO and C3OMeImAcO-DMSO is more sensitive to variation of T than of χDMSO; the inverse is observed for the quaternary ammonium ILs. Using BuMeImAcO, AlBzMe2NAcO, and molecular dynamics simulations, we attribute the difference in IL efficiency to stronger SF-IL hydrogen bonding with the former IL, which is coupled with the difference in the molecular volumes and the rigidity of the phenyl ring of the latter IL. The order of SF dissolution is BuMeImAcO-DMSO > C3OMeImAcO-DMSO; this was attributed to the formation of intramolecular H-bonding between the ether oxygen in the side chain of the latter IL and the relatively acidic hydrogens of the imidazolium cation. Using DOE, we were able to predict values of SF-m%; this is satisfactory and important because it results in economy of labor, time, and material.

| S-EPMC8747519 | biostudies-literature

Solubility of Azilsartan in Methanol, Ethanol, Acetonitrile, <i>n</i>-Propanol, Isopropanol, Tetrahydrofuran, and Binary Solvent Mixtures between 293.15 and 333.15 K.

Project description:A precise determination method of azilsartan solubility between 293.15 and 333.15 K in several ordinary solvents and some of their aqueous mixtures was established by high-performance liquid chromatography. In all tested solvents, its solubility shows exponential growth with the increase in temperature. This trend is especially pronounced in methanol and ethanol. The order of solubility of azilsartan can be expressed as ethanol > tetrahydrofuran > ethanol/water (8/2, v/v) > methanol > methanol/water (8/2, v/v) > n-propanol > isopropanol > ethanol/Water (5/5, v/v) > acetonitrile. The solubility data of azilsartan were well correlated by the λh model. Moreover, the thermodynamic data including the dissolving enthalpy, entropy, and Gibbs free energy of azilsartan in each solvent were calculated which is crucial to its preparation technology study.

| S-EPMC7097992 | biostudies-literature

Choline-Amino Acid Ionic Liquids as Green Functional Excipients to Enhance Drug Solubility.

Project description:The development of effective forms to incorporate poorly soluble drugs into delivery systems remains a problem. Thus, it is important to find alternatives such as finding excipients that increase drug solubility. Ionic liquids (ILs), particularly choline-based ILs, have been studied as solubility enhancers in drug delivery systems. Nonetheless, to acknowledge this property as a functionality, it needs to be proven at non-toxic concentrations. Hence, herein two choline-amino acid ILs were studied as functional excipients by evaluating their influence on the solubility of the poorly water-soluble ferulic acid and rutin, while considering their safety. The solubility of the drugs was always higher in the presence of the ILs than in water. Ionic liquids did not affect the radical scavenging activity of the drugs or the cell viability. Moreover, stable oil-in-water (O/W) emulsions were prepared containing each drug and the ILs, allowing a significantly higher drug loading. Globally, our results suggest that choline-based ILs may act as green functional excipients, since at non-toxic concentrations they considerably improve drug solubility/loading, without influencing the antioxidant activity of the drugs, the cell viability, or the stability of the formulations.

| S-EPMC6321021 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data