Solubility Of Testosterone Research Articles

Design, synthesis, and characterization of pharmaceutical cocrystal of testosterone and 4, 4-dihydroxybiphenyl

Testosterone (T) is a steroid hormone with poor solubility, which can maintain muscle strength and enhance physical strength. The cocrystal (T·DOD·H2O) of testosterone and 4, 4-dihydroxyl biphenyl (DOD) was synthesized using solution crystallization technology in the stoichiometric ratio of 1: 1, and then characterized by single crystal X-ray diffraction (SXRD), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetry (TG). Subsequently, the solubility and powder dissolution rate of the cocrystal were tested, and the results show that the solubility of the cocrystal is increased by 8.37 times and the powder dissolution rate is risen to 34.1 times compared with the pure testosterone. Obviously, the solubility of testosterone is highly increased by pharmaceutical cocrystal, which is a potential strategy of improving poorly soluble active pharmaceutical ingredients.

Solubilities of Testosterone, Methyltestosterone and Nandrolone in Alkanols

Solubilities of Testosterone, Methyltestosterone and Nandrolone in Alkanols

Some solute-solvent complexes involving testosterone and testosterone propionate.

Solute-solvent interactions have been studied by observing the influences of carbon tetrachloride, carbon disulphide, ethyl oleate, isopropyl myristate and octanol on the solubilities of testosterone and testosterone propionate in an inert solvent (cyclohexane). Complexation with testosterone was detected, but there was no evidence of complexation between testosterone propionate and these solvents. The solvent-induced infrared shifts were due to non-specific solvent effects. The existence of solute-solvent complexes between the two solutes and chloroform, previously detected by infrared absorption, was confirmed. The solubility technique, which has previously only been used with solid complexing agents, is adaptable to liquid complexing agents, but has limitations.

Feasibility of on-line supercritical fluid extraction of steroids from aqueous-based matrices with analysis via gas chromatography-mass spectrometry.

The solubility of testosterone, boldenone, androstenone, etiocholanolone, and epitestosterone are measured in pure supercritical CO2. Testosterone exhibited the highest solubility in supercritical CO2. The solubility of all steroids except epitestosterone increased by one order of magnitude with increasing pressure from 100 to 400 atm. Epitestosterone had the lowest solubility in supercritical CO2 and its solubility was not affected by pressure. The extraction efficiency of steroids from an aqueous saline environment exceeded 95%. Because of the partial solubility of water in supercritical CO2, the addition of a moisture trap after the aqueous vessel is necessary to prevent the plugging and deterioration of the gas chromatographic (GC) column. It is demonstrated that on-line supercritical fluid extraction-GC-mass spectrometry is feasible for the quantitative extraction and analysis of steroids from both saline and urine solutions. However, it is determined that the adsorbent vessel filled with Hydromatrix is not sufficient to trap all the moisture, and after 3 to 4 extractions, the GC column efficiency lowered.

Release of testosterone from an osmotic pump tablet utilizing (SBE) 7m-β-cyclodextrin as both a solubilizing and an osmotic pump agent

A controlled porosity osmotic pump system for poorly water soluble drugs has been developed using sulfobutyl ether-β-cyclodextrin sodium salt, (SBE) 7m-β-CD, which can act as both a solubilizing and an osmotic agent. The release of testosterone, a poorly water soluble drug (0.039 mg/ml at 37°C), was evaluated using a new model device. The effect of (SBE) 7m-β-CD as the solubilizing and osmotic pump agent was compared with hydroxypropyl-β-cyclodextrin (HP-β-CD), a neutral cyclodextrin, and a sugar mixture (osmotic agent only). Testosterone release from the device was significantly faster with (SBE) 7m-β-CD than with HP-β-CD or the sugar mixture. The solubility of testosterone in the device increased to 76.7 mg/ml through complexation with (SBE) 7m-β-CD in the imbibed water. It appears that testosterone release from the device in the presence of (SBE) 7m-β-CD was mainly due to osmotic pumping while for HP-β-CD the major contribution appears to be due to diffusion. In the case of the sugar mixture, testosterone was poorly released, presumably due to the absence of a solubilizer. Therefore, it was concluded that (SBE) 7m-β-CD provides novel properties for the development of controlled- porosity osmotic pump tablets for poor solubility drugs.

Testosterone Skin Permeation Enhancement by Menthol through Formation of Eutectic with Drug and Interaction with Skin Lipids

□ The aim of this investigation was to elucidate the mechanism of skin permeation enhancement of the lipophilic drug, testosterone, by menthol. Menthol was found to form eutectic mixtures with testosterone, cholesteryl oleate, and ceramides. DSC measurements showed that menthol drastically lowers the Tm of testosterone, from 153.7 to 39.9°C. The decrease in Tm resulted in an increase in the solubility of testosterone in an aqueous ethanol vehicle by 2.8-fold, which caused a corresponding 2.8-fold increase in the flux of testosterone. A further increase in skin flux, to eight times the base line, could be attributed to the effect of menthol on the skin barrier properties. This assumption is supported by DSC results showing that menthol decreases the Tm of cholesteryl oleate and ceramides and modifies the thermogram profile of isolated stratum corneum. The results of this investigation indicate that menthol affects skin permeation by a dual mechanism: by forming a eutectic with the penetrating compound, thereby increasing its solubility, and by altering the barrier properties of the stratum corneum. Moreover, this study indicates that both types of interactions must be taken into consideration when using chemical enhancers and that decreasing the melting temperature of the permeant through formation of a eutectic could be one approach for increasing solubility and permeation rates.

Extended Hildebrand Solubility Approach: Testosterone and Testosterone Propionate in Binary Solvents

Solubilities of testosterone and testosterone propionate in binary solvents composed of the inert solvent, cyclohexane, combined with the active solvents, chloroform, octanol, ethyl oleate, and isopropyl myristate, were investigated with the extended Hildebrand solubility approach. Using multiple linear regression, it was possible to obtain fits of the experimental curves for testosterone and testosterone propionate in the various binary solvents and to express these in the form of regression equations. Certain parameters, mainly K and log α2, were employed to define the regions of self-association, nonspecific solvation, specific solvation, and strong solvation or complexation.

Micellar Solubilization of Testosterone II: In Aqueous Solutions of Some Ionic Surfactants

The solubility of testosterone at 25° was determined in aqueous solutions containing varying concentrations of dodecyltrimethylammonium bromide (DTAB), hexadecyl-trimethylammonium bromide (HTAB), and potassium laurate (KL). After the initial stages of solubilization, a linear relationship was observed between the amount of testosterone solubilized and the molar concentration of the surfactant. The order of increasing solubilizing capacity was DTAB < HTAB < KL. The environment of solubilized testosterone, as investigated by the Z-value method, was found to be quite polar in all cases. At low concentrations of DTAB and HTAB the Z value was similar to that in water. As the concentration of the quaternary ammonium bromides increased, a precipitous drop in Z value, corresponding to a sudden decrease in environmental polarity, was observed in the region of the critical micelle concentration. With further increase in the concentration of DTAB and HTAB the Z value remained reasonably constant. In low KL concentrations the Z value of the testosterone environment was higher (more polar) than in water. With increasing concentrations of KL the Z value displayed behavior similar to that in DTAB and HTAB. In general, solutions of ionic surfactants showed higher Z values than those of the nonionic surfactants examined previously.

Micellar solubilization of testosterone I In aqueous solutions of polysorbates

The solubility of testosterone in aqueous solutions of partially purified polysorbate 20, 40, and 60 was determined by measuring the area under the ultraviolet spectral peaks. There was solubilization below the critical micelle concentration. A linear relationship was observed between the amount of testosterone solubilized and the per cent polysorbate concentration. Polysorbate 60 exhibited the greatest solubilizing capacity and polysorbate 20 the least. The Z-value method for determining solvent polarity was employed to investigate the polarity of the environment in which testosterone was solubilized. At low polysorbate concentrations the Z-value was similar to that in water. As the polysorbate concentration increased, the Z-value decreased. This decrease in Z-value paralleled the increase in solubility of testosterone.

Interactions of testosterone with amino acids

The solubility of testosterone in buffered solutions of 18 l-amino acids was determined. In solutions of l-tryptophan, l-tyrosine, l-phenylalanine, l-histidine, l-arginine, and l-lysine a significant increase was obtained above that observed in buffer alone at the corresponding ionic strength. The largest effect was obtained with l-tryptophan. A slight increase in solubility was noted in solutions of l-methionine and l-proline. With the other ten amino acids no increase was noted.

THE METABOLISM OF INTRAVENOUS TESTOSTERONE BY EXPERIMENTAL ANIMALS1,2

ALTHOUGH it has never been isolated from blood, testosterone is usually considered to be the circulating androgen secreted by the testis. With the demonstration by Bischoff (1948) of the high solubility of testosterone in serum albumin, it became possible to administer large doses of free testosterone dissolved in serum albumin intravenously and to study the fate, distribution, and excretion of circulating testosterone.