Significant Enhancement In Solubility Research Articles

N-alkyl polybenzimidazole: Effect of alkyl chain length

Despite the presence of bulk literature on polybenzimidazole (PBI), unavailability of readily soluble and processable PBI remains as the tallest challenge for the end-use. N-alkyl PBIs (N-PBIs) were synthesized by grafting the alkyl chain in the imidazole backbone to resolve this key constrain. The chain length of substituted alkyl groups was varied to evaluate the influence of chain size on the structures and properties of N-PBIs. Significant enhancement of solubility of N-PBIs compared to parent PBI in formic acid offered the opportunity to fabricate the homogeneous mechanically tough membranes with minimal efforts. The substituted long alkyl chains pushes apart the PBI chains and hence increases the face-to-face packing distance by breaking the self-association between the chains; resulted into less rigid highly soluble N-PBIs. Alkyl chain length dependent weight loss at ∼300°C, presence of two glass transition temperatures and peculiar deep rubbery modulus in storage modulus vs. temperature plots resembled the copolymer molecular structure of N-PBIs. Hydrophobic character of alkyl chains and loosely packed structure of N-PBIs facilitated decrease in water uptake and swelling of the N-PBI membranes compared to parent PBI membrane. The temperature dependent proton conductivity of PA loaded N-PBIs membranes were found to be satisfactory.

Formulation and in Vitro Evaluation of Mouth Dissolving Tablet of Olanzapine Using Solid Dispersion Technique

In the present investigation solid dispersion of olanzapine has been prepared to improve its solubility. Further, using solid dispersion, mouth dissolving tablet was prepared to overcome the problem of swallowing. A Simplex Lattice design was applied using three factors, i.e. superdisintegrants like croscarmellose sodium(X 1 ) crospovidone(X 2 ), and sodium starch glycolate(X 3 ) in tablet formulation. Disintegration time and T 50 (Time required to 50% drug release) taken as responses. Solid dispersion showed significant enhancement in solubility of olanzapine. For mouth dissolving tablet, batch containing 5% croscarmellose sodium alone had minimum disintegration time (44 sec.) and faster drug release (T 50 : 40 sec) compared to other batches.

The effect of prolonged incubation time on the interaction between PAMAM dendrimers and iminodiacetic acid derivatives

Dendrimers, highly branched spherical polymers, are known for their ability to act as solubility enhancers of various types of drugs. In the present study, we investigated the potential of poly(amidoamine) (PAMAM) dendrimers G1-G4 in concentration from 0 to 10 mg/mL for solubility of two iminodiacetic acid derivatives after prolonged (72 hour) incubation time. The experiments were conducted by means of the equilibrium solubility method which is based on the spectrophotometric measurements of compounds’ absorbance solubilized in the presence of PAMAM dendrimers. We reported that PAMAM dendrimers contribute to significant solubility enhancement of tested compounds. This effect is concentration- and generation- dependent. The results of solubility studies after 72 h incubation time suggest that the interactions between iminodiacetic acid derivatives and PAMAM dendrimers, mainly electrostatic and hydrophobic, are stable in aqueous environment.

Evaluation of poly(amidoamine) dendrimers as potential carriers of iminodiacetic derivatives using solubility studies and 2D-NOESY NMR spectroscopy

The interactions between dendrimers and different types of drugs are nowadays one of the most actively investigated areas of the pharmaceutical sciences. The interactions between dendrimers and drugs can be divided into: internal encapsulation, external electrostatic interaction, and covalent conjugation. In the present study, we investigated the potential of poly(amidoamine) (PAMAM) dendrimers for solubility of four iminodiacetic acid derivatives. We reported that PAMAM dendrimers contribute to significant solubility enhancement of iminodiacetic acid analogues. The nature of the dendrimer–drug complexes was investigated by 1H NMR and 2D-NOESY spectroscopy. The 1H NMR analysis proved that the water-soluble supramolecular structure of the complex was formed on the basis of ionic interactions between terminal amine groups of dendrimers and carboxyl groups of drug molecules, as well as internal encapsulation. The 2D-NOESY analysis revealed interactions between the primary amine groups of PAMAM dendrimers and the analogues of iminodiacetic acid. The results of solubility studies together with 1H NMR and 2D-NOESY experiments suggest that the interactions between PAMAM dendrimers of generation 1–4 and derivatives of iminodiacetic acid are based on electrostatic interactions and internal encapsulation. Electronic supplementary material The online version of this article (doi:10.1007/s10867-012-9277-5) contains supplementary material, which is available to authorized users.

Preparation, Characterization and <i>in Vivo</i> Evaluation of Antihyperglycemic Activity of Microwave Generated Repaglinide Solid Dispersion

The influence of microwave technology on the in vitro dissolution rate and in vivo antihyperglycemic activity of a poorly water soluble drug, repaglinide (RG) was studied. Solid dispersions were prepared by conventional fusion method and microwave method using poloxamer 188. The dispersions were characterized by solubility study, dissolution study, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). Microwave generated solid dispersions exhibited remarkable improvement in solubility and dissolution rate compared to that of pure RG. Results of DSC, XRD and SEM study showed conversion of crystalline form of RG to amorphous form. In vivo studies revealed that the microwave generated solid dispersion showed significant improvements in antihyperglycemic activity as compared to RG alone, thus confirming the advantage of improved pharmacological activity of RG by microwave method. In conclusion, microwave method could be considered as simple, efficient and solvent free promising alternative method to prepare solid dispersion of poorly water soluble drug RG with significant enhancement in solubility, dissolution rate and antihyperglycemic activity.

A Bifunctional Dimethylsulfoxide Substitute Enhances the Aqueous Solubility of Small Organic Molecules

An oxetane-substituted sulfoxide has demonstrated potential as a dimethylsulfoxide substitute for enhancing the dissolution of organic compounds with poor aqueous solubilities. This sulfoxide may find utility in applications of library storage and biological assays. For the model compounds studied, significant solubility enhancements were observed using the sulfoxide as a cosolvent in aqueous media. Brine shrimp, breast cancer (MDA-MB-231), and liver cell line (HepG2) toxicity data for the new additive are also presented, in addition to comparative IC(50) values for a series of PKD1 inhibitors.

Equilibrium solubilities of a p-toluenesulfonamide and sulfanilamide mixture in supercritical carbon dioxide with and without ethanol

Supercritical separation processes for a multi-component mixture of solutes are of practical interest. In this study, the experimental equilibrium solubilities of two solute mixtures, p-toluenesulfonamide ( p-TSA) and sulfanilamide (SNA), in supercritical carbon dioxide (SC CO 2) were measured at temperatures of 308, 318 and 328 K and pressures in the range of 11.0–21.0 MPa using a dynamic flow method. The effect of cosolvent on the multi-component system was investigated by the addition of a 3.5 mol% ethanol. In the ternary system ( p-TSA + SNA + CO 2), the solubility of SNA increased as compared to its binary system (SNA + CO 2), while the solubility of p-TSA decreased. In the quaternary system ( p-TSA + SNA + ethanol + CO 2), a significant solubility enhancement was observed for both p-TSA and SNA. The selectivity, which is thought to imply the intermolecular interactions between p-TSA and SNA, was also enhanced by the presence of ethanol so that the two solutes could be separated by a max. purity of 99.4%. The influence of the hydrogen bond interaction on solubility was discussed. The equations of Chrastil, Méndez-Santiago and Teja, and their modified forms were used to correlate the experimental data.

Co-solvent solubilization of some poorly-soluble antidiabetic drugs

Co-solvent solubilization approach has been used to enhance the solubility of seven antidiabetic drugs: gliclazide, glyburide, glipizide, glimepiride, repaglinide, pioglitazone, and roziglitazone. Solubility in water, phosphate buffer (pH 7.4), six co-solvent solutions prepared in water as well as phosphate buffer (pH 7.4) and pH-solubility profile of various drugs have been determined at 25°C. Aqueous solubility of various drugs was found to be less than 0.04 mg/mL. Solubility of gliclazide, glipizide and repaglinide increased by 3-6 times by using phosphate buffer (pH 7.4) as solvent. Solubility enhancement by pH modification was not sufficient. Significant enhancement in solubility could be achieved by the use of co-solvents. The combined effect of co-solvent and buffer was synergistic and enormous increase in solubility of sulfonylureas and repaglinide could be achieved. In the case of glitazones, however, co-solvent alone caused significant enhancement; the presence of buffer had negative effect on the solubilization potential of the co-solvents. Up to 763, 316, 153, 524, 297, 792 and 513 times increase in solubility could be achieved in the case of gliclazide, glyburide, glimepiride, glipizide, repaglinide, pioglitazone and rosiglitazone, respectively.

The complexation of aqueous metal ions relevant to biological applications. 1. Poorly soluble zinc salts and enhanced solubility with added amino acid

The effect of added amino acid (glycine, alanine and serine) on the solubility of zinc citrate, zinc succinate and zinc oxalate was investigated. Equilibrated solutions were prepared and titrated to endpoint at pH 5.5 with Na2EDTA using Xylenol Orange indicator. In every case, a significant enhancement in solubility was seen as the amino acid increased from 1 to 50 molar excess. The increase was non-linear, and, with zinc succinate, showed saturation effects. In these cases, solution composition may be more complicated than initially thought, including mixed-ligand complexes and increasing percent free metal ion as the proportion of amino acid increases.

Molecular and Thermodynamic Aspects of Solubility Advantage from Solid Dispersions

The solubility behavior of solid dispersions of two drugs with similar structures was studied. Valdecoxib (VLB) and etoricoxib (ETB) were used as model drugs, and their solid dispersions were prepared with 1, 2, 5, 10, 15, and 20% w/w poly(vinylpyrrolidone) (PVP) by the quench cooling method. The interactions between the drug and polymer molecules were studied by Fourier transform infrared spectroscopy (FT-IR). The thermodynamic aspects of solubility behavior were studied by plotting van't Hoff plots. Both the drugs showed significant differences in their solubility behavior. In the case of VLB, solubility was found to increase significantly with increasing PVP concentration. ETB however did not show any significant solubility enhancement and was found to have decreased solubility at high PVP concentrations. H-bonding interactions were established between VLB and PVP molecules, while none were observed in ETB-PVP dispersions. Solution thermodynamics of amorphous and crystalline forms of both the drugs were studied by van't Hoff plots. The results obtained showed very high negative value of Gibbs free energy for VLB as compared to ETB, thus demonstrating high spontaneity of VLB solubilization. Entropy of amorphous VLB was found to be highly favorable, while being slightly unfavorable for ETB. From this study H-bonding interactions were found to play a major role in dictating the solubility behavior of these drugs from solid dispersions.

Oxygenated fuel induced cosolvent effects on the dissolution of polynuclear aromatic hydrocarbons from contaminated soil

The cosolvent-induced dissolution of polynuclear aromatic hydrocarbons (PAHs) from contaminated soil caused by oxygenated fuel spills was studied. Oxygenated fuel induces a solvent flushing effect on the contaminated soil due to the high content of oxygenated compounds (i.e., methanol, ethanol, and methyl tert butyl ether (MTBE)). The miscible displacement techniques were applied to evaluate the increased potential for secondary contamination in an impacted site. Significant solubility enhancement of the 18 PAHs monitored during fuel spill simulation and cosolvent flushing is clearly evident when compared to normal water dissolution. The breakthrough concentration profile for each PAH constituent was integrated over the cumulative effluent volume (i.e., the zeroth moment) to determine the total PAH mass removed during the experiment. The removal efficiency of PAHs ranges from 46.6% to 99.9% in three oxygenated fuels (i.e., M85, E85, and oxygenated gasoline) during the fuel spill. Several factors including hydrophobicity of compounds, nonequilibrium dissolution due to nonuniform coal tar distribution, and heterogeneous media properties affect the oxygenated compound-induced dissolution process. This study provides a basis to predict the facilitated transport of hydrophobic organic compounds from subsurface environment due to the cosolvent effects of oxygenated fuels.

Arsenic(III) carbonate complexing

A recent hypothesis that As(III) forms strong complexes with (bi)carbonate is tested by measuring the solubility of As 2O 3 in concentrated (up to 0.72 m) bicarbonate solutions at near-neutral pH and 25.0 ± 1.8 °C. A small, but statistically significant solubility enhancement is observed in NaHCO 3-containing solutions compared to NaCl solutions of essentially the same ionic strength. The effect is well-explained by formation of a single complex: As ( OH ) 3 0 + HCO 3 - = As ( OH ) 2 CO 3 - + H 2 O , K c = 0.22 ± 0.04 (corrected to infinite dilution). This complex’s small stability constant value is consistent with a published, quantum-based computational prediction. The measurements also yield a value for the solubility of arsenolite that agrees reasonably with recently reported values: 1 / 2 As 2 O 3 ( arsenolite ) + 3 / 2 H 2 O = As ( OH ) 3 0 , K s = 0.178 ± 0.004 (also corrected to infinite dilution). The new data show that As(III) carbonate complexes will be negligible at carbonate concentrations found in most natural waters, but could be significant, though minor, in extremely carbonate-rich waters, such as found in interior drainage basins.

Solubility of CF2-Modified Polybutadiene and Polyisoprene in Supercritical Carbon Dioxide

The cloud-point behavior of fluorinated polyisoprenes (FPI) and fluorinated polybutadienes (FPBD) in supercritical fluid (SCF) CO2 are reported at temperatures from 60 to 170 °C and pressures from 1000 to 3000 bar. These fluorinated polymers were prepared by the addition of difluorocarbene (CF2) to the parent polydienes yielding a gem-difluorocyclopropane repeating unit, a segment containing both fluorine and a significant dipole moment. Neither the unmodified polyisoprene starting material nor the hydrogenated variant dissolves in CO2 up to temperatures of 155 °C and pressures of 2600 bar. Both FPI and FPBD dissolve in CO2, but pressures in excess of 1000 bar are needed to obtain a single phase. The PFI and PFBD cloud-point curves exhibit temperature minima at approximately 60 and 80 °C, respectively, likely due to an increase in CO2−CO2 and polymer−polymer interactions relative to polymer−CO2 interactions. As the amount of CF2 incorporation in FPI samples decreases, the cloud-point curves shift to higher pressures and to higher temperatures. In a series of FPBD samples, an increase in cloud-point pressure with increase in molecular weight is initially large for molecular weights less than 105 and then becomes much less at higher molecular weights, as also observed for other polymer−SCF solvent mixtures. This methodology for incorporation of fluorine into macromolecules leads to significant enhancement of solubility in CO2.

Aqueous Solubility of Diclofenac Diethylamine in the Presence of Pharmaceutical Additives: A Comparative Study with Diclofenac Sodium

Aqueous solubility of diclofenac diethylamine (DDEA), a nonsteroidal anti-inflammatory drug currently formulated as a topical emulgel, was studied in the presence of pharmaceutical additives and compared with diclofenac sodium (DS). Electrolytes at low concentrations exhibited a salting-in effect on DDEA with peak solubility that was attributed to the association of DDEA into micelles, followed by a salting-out effect at higher concentrations, by which structure formation by DDEA molecules increased and precipitation occurred. For DS, which is not capable of forming micelles, the salting-out effect was dominant due to the common ion effect. Cosolvents displayed significant enhancement in solubility of both salts except glycerol, which showed a slight increase in solubility of DDEA and a decrease in solubility of DS due to transformation into the less soluble hydrate form. Ethanol and polyethylene glycol (PEG) 400 cosolvent systems at all concentrations showed positive deviations from the log-linear solubility equation. In the case of propylene glycol (PG) cosolvent systems, negative deviations were observed at low volume fractions of cosolvent, while positive deviations were observed at high volume fractions of cosolvent for DS and DDEA. The parent drug, being less ionizable and highly nonpolar, showed negative deviations up to 90% PG content. Thus, the positive deviations for DS and DDEA could be attributed to the more ionizable carboxylic group and its higher ability for hydrogen bonding at higher fractions of cosolvent. Polyvinylpyrrolidone (PVP) and PEG4000 or PEG6000 enhanced the solubility of DS and DDEA, with PVP exerting higher solubilizing efficiency and DS showing better solubility than DDEA. Solubilities of DS in Tween 80 (T80) and Pluronic F-127 (PF127) aqueous solutions were almost similar, while the solubility of DDEA in the presence of T80 was higher than the solubility in the presence of PF127. DS appeared to be located more in the polyoxyethylene mantle of the micelles, while DDEA was located more in the core of the micelles.

Solubilities of Mixed Hydroxybenzoic Acid Isomers in Supercritical Carbon Dioxide

Studies of the extraction of solid mixtures with supercritical fluids (SCFs) demonstrate that solute−solute interactions in the SCF phase can be significant. To further explore such interactions, the solubilities of various mixtures of hydroxybenzoic acid (HBA) isomers in supercritical CO2 were determined. Solubility data are reported at pressures ranging from 101 to 203 bar and for temperatures of 318 K and 328 K. Significant solubility enhancements were observed for m-HBA and p-HBA in systems containing the ortho isomer. The degree of solubility enhancement obtained is possibly the result of hydrogen bonding between the isomers in the SCF phase. The solubility data were correlated with a modified form of the Peng−Robinson equation of state.

Water solubility enhancement of some organic pollutants and pesticides by dissolved humic and fulvic acids

Water solubility enhancements by dissolved humic and fulvic acids from soil and aquatic origins and by synthetic organic polymers have been determined for selected organic pollutants and pesticides (p,p'-DDT,2,4,5,2',5'-PCB, 2,4,4'-PCB, 1,2,3,-trichlorobenzene, and lindane). Significant solubility enhancements of relatively water-insoluble solutes by dissolved organic matter (DOM) of soil and aquatic origins may be described in terms of a partition-like interaction of the solutes with the microscopic organic environment of the high-molecular-weight DOM species; the apparent solute solubilities increase linearly with DOM concentration and show no competitive effect between solutes. The K/sub dom/ values of solutes with soil-derived humic acid are approximately 4 times greater than with soil fulvic acid and 5-7 times greater than with aquatic humic and fulvic acids. The effectiveness of DOM in enhancing solute solubility appears to be largely controlled by the DOM molecular size and polarity. The relative inability of high-molecular-weight poly(acrylic acids) to enhance solute solubility is attributed to their high polarities and extended chain structures that do not permit the formation of a sizable intramolecular nonpolar environment. 41 references, 6 figures, 3 tables.