PubMed Health⌕ Search

Biomedical subjects

S H Yalkowsky

Publications and source records attributed to S H Yalkowsky.

At least 73 records · Page 4Linked to original sources
PubMed1990

Melting point, boiling point, and symmetry.

The relationship between the melting point of a compound and its chemical structure remains poorly understood. The melting point of a compound can be related to certain of its other physical chemical properties. The boiling point of a compound can be determined from additive constitutive properties, but the melting point can be estimated only with the aid of nonadditive constitutive parameters. The melting point of some non-hydrogen-bonding, rigid compounds can be estimated by the equation MP = 0.772 * BP + 110.8 * SIGMAL + 11.56 * ORTHO + 31.9 * EXPAN - 240.7 where MP is the melting point of the compound in Kelvin, BP is the boiling point, SIGMAL is the logarithm of the symmetry number, EXPAN is the cube of the eccentricity of the compound, and ORTHO indicates the number of groups that are ortho to another group.

Chemical Phenomena↗
PubMed1990

Particle size and content uniformity.

The requirements of the USP Content Uniformity test are translated into physical and mathematical parameters. Assuming spherical particle sizes with a log normal distribution, the mean particle size and particle size distribution required to insure a high probability of passing the content uniformity test are calculated. On the basis of these calculations it is shown that satisfactory tablets of low doses cannot be manufactured from a drug that does not meet certain particle size distribution specifications. It is recommended that particle size specifications for low dose drugs include a requirement for a limit to size distribution.

Particle Size↗
PubMed1989

Enhanced intestinal absorption of cyclosporine in rats through the reduction of emulsion droplet size.

The intestinal absorption of cyclosporine was measured in situ in rats using an olive oil emulsion prepared by either stirring or homogenization. The surface area of the homogenized dosage form was twice that of the stirred dosage form. The apparent permeability of cyclosporine from the homogenized emulsion was about twice that of the emulsion prepared by stirring. The examination of absorption in different intestinal segment lengths suggested the presence of an "absorption window." The absorption of cyclosporine appeared to be concentration independent and, therefore, non-carrier mediated. The dependence of absorption upon the intestinal perfusion rate suggested that the stagnant aqueous layer is the rate-limiting barrier in cyclosporine absorption. These results indicate that the bioavailability of cyclosporine administered in an emulsion can possibly be increased by enhancing its rate of absorption through the reduction of droplet size.

Animals↗
PubMed1988

Water solubility: a critique of the solvatochromic approach.

The reasoning and some of the assumptions behind the solvatochromic approach to water solubility are evaluated, particularly in relation to its claims. It is shown that the contribution of the pi term is uncertain, and that it can be dropped from the correlation without substantially affecting the degree of fit. The solvatochromic method is compared with the long-standing relationship between solubility and the octanol-water partition coefficient, and it is demonstrated that the latter offers a far superior route to solubility estimation.

Chemistry, Pharmaceutical↗
PubMed1988

Solubility and partitioning. IX: Solubility of hydantoins in water.

An expression for estimating the aqueous solubility of weak electrolytes under different conditions of temperature and pH has been proposed in a previous publication. The expression, based on the additivity of free energy, separates solubility into three independent contributions. In the present work, the equation is tested with a different set of 18 solutes within the range of temperature of 20 to 50 degrees C and of pH of 1 to 10. The results show that the theoretical relationship between aqueous solubility and the three independent contributions used in the equation is in excellent agreement with the experimental data.

Chemical Phenomena↗
PubMed1987

Solubility and partitioning. VII: Solubility of barbiturates in water.

The solubility equation of Yalkowsky was used to estimate the aqueous solubility of 33 barbiturates in the temperature range of 5 to 45 degrees C. The equation was extended by adding a term which accounts for the effect of pH on the solubility of the drug. The extended equation is successful in estimating the aqueous solubility of this series of drugs under different conditions of temperature and pH. The results indicate that the extended equation can be used to estimate the aqueous solubility of nonelectrolytes as well as weak electrolytes.

Barbiturates↗
PubMed1987

Cosolvency and deviations from log-linear solubilization.

The solubilities of three nonpolar drugs, phenytoin, diazepam, and benzocaine, have been measured in 14 cosolvent-water binary mixtures. The observed solubilities were examined for deviations from solubilities calculated by the equation log Sm = f log Sc + (1 - f) log Sw, where Sm is the solubility of the drug in the cosolvent-water mixture, Sc is the solubility of the drug in neat cosolvent, f is the volume fraction of cosolvent, and Sw is the solubility of the drug in water. When presented graphically, the patterns of the deviations were similar for all three drugs in mixtures of amphiprotic cosolvents (glycols, polyols, and alcohols) and water as well as nonpolar, aprotic cosolvents (dioxane, triglyme, dimethyl isosorbide) and water. The deviations were positive for phenytoin and benzocaine but negative for diazepam in mixtures of dipolar, aprotic cosolvents (dimethylsulfoxide, dimethylformamide, and dimethylacetamide) and water. The source of the deviations could not consistently be attributed to physical properties of the cosolvent-water mixtures or to alterations in the solute crystal. Similarities between the results of this study and those of previous investigations suggest that changes in the structure of the solvent play a role in the deviations from the expected solubilities.

Benzocaine↗
PubMed1987

Cosolvency and cosolvent polarity.

The solubilities of three poorly soluble drugs, phenytoin, benzocaine, and diazepam, in cosolvent-water mixtures have been previously shown to be approximated by the log-linear solubility equation; log (Sm/Sw) = sigma f, where Sm and Sw represent the solubilities of the drug in the solvent mixture and water, respectively, f is the volume fraction of cosolvent, and sigma is the slope of a plot of log (Sm/Sw) vs f. In this study, the slopes, sigma, of the solubility plots were related to indexes of cosolvent polarity including the dielectric constant, solubility parameter, surface tension, interfacial tension, and octanol-water partition coefficient. Those polarity indexes that reflect the cohesive properties of the solvents such as the solubility parameter and interfacial tension resulted in the highest correlations with the slope, sigma. The hydrogen bonding ability of the neat cosolvent, expressed as the density of proton donating groups (HBD) or acceptor groups (HBA), was also found to be highly correlated with sigma. Additional relationships derived from theories involving solubility parameters and interfacial tension provide improved correlations between the cosolvent polarity and sigma. These results and analysis provide the basis for the estimation from physicochemical parameters of the appropriate type and amount of cosolvent needed to solubilize nonpolar drugs.

Benzocaine↗
PubMed1987

A new parenteral emulsion for the administration of taxol.

Taxol (NSC-125973) is a poorly soluble plant product that exhibits excellent antimitotic properties. This study involves the development of a new formulation for taxol. The stability of taxol in a 50% triacetin emulsion as well as possible methods of intravenous administration of this dosage form was examined. A stable emulsion was found at taxol concentrations of 10 and 15 mg/ml of emulsion. The 50% triacetin emulsion showed an intravenous LD50 of 1.2 ml/kg in Swiss-Webster mice. The 10 mg/ml taxol formulation was demonstrated to be stable upon addition to 5% dextrose iv fluids provided that small packing systems were used. The taxol-triacetin emulsion can also be intravenously injected at various rates, and it may prove to be a useful formulation for taxol.

Alkaloids↗
PubMed1985

Solubilization by cosolvents I: organic solutes in propylene glycol-water mixtures.

An equation describing solubilization in aqueous systems by cosolvents was developed by treating a mixed solvent as a linear combination of its components. This equation can successfully explain both the exponential increases and the exponential decreases in aqueous solubility that are frequently observed with the addition of cosolvent. It also provides a means of estimating to what extent a particular drug can be solubilized and how much cosolvent would be required to accomplish a particular degree of solubilization.

Chemical Phenomena↗
PubMed1985

Multiple-hole approach to zero-order release.

We describe an approach to zero-order drug delivery systems that utilizes a device consisting of multiple holes uniformly distributed in an impermeable membrane. The interior of the device is filled with a suspension of a drug in a polymeric matrix. Near zero-order release is attained by using the proper density and configuration of holes on the surface of the device.

Chemistry, Pharmaceutical↗
PubMed1984

Solubility of fatty acids and other hydrophobic molecules in liquid trioleoylglycerol.

The fat solubilities of some long chain fatty acids, alcohols, alkanes, and triacyglycerols, and of some aromatic, chlorinated aromatic, and chlorinated aliphatic hydrocarbons were measured in trioleoylglycerol. Above their melting temperature, all test compounds are theoretically miscible with liquid fat. Below their melting temperature the solubility of all test compounds can be estimated by the equation: log (mole fraction solubility) = (Formula: see text) where delta Sf, the entropy of fusion, can be estimated from chemical structure according to Yalkowsky and Valvani (J. Pharm. Sci. 1980. 69:912-922), and the melting point (Tm) is either known or experimentally determined. For long chain compounds, solubility in trioleoylglycerol dropped precipitously with an increase in melting point. For the aromatic and chlorinated compounds, the drop was more gradual. Since the entropy of fusion of rigid aromatic compounds is approximately 13.5 e.u. at room temperature, their solubility in triacylglycerol is a linear function of melting point.

Alcohols↗
PubMed1983

Solubility and partitioning VI: octanol solubility and octanol-water partition coefficients.

A simple equation for the estimation of the aqueous solubility of crystalline solutes was previously derived based on the assumption that the presence of water does not significantly alter the crystal properties of the solute. The data presented verify the solubility equation for a set of 36 nonelectrolytes and weak electrolytes. Using the same set of solutes, the two major assumptions used to derive the equation were also verified: that the octanol solubility of nonelectrolytes is exponentially proportional to the melting point of the solute and that the octanol-water solubility ratio is a good approximation of the octanol-water partition coefficient.

Chemical Phenomena↗
PubMed1983

In vitro method for detecting precipitation of parenteral formulations after injection.

Many injectable formulations currently on the market, including diazepam and alprazolam, utilize one or more cosolvents to solubilize the active constituents. On injections into an aqueous medium, some of these components tend to precipitate. A simple procedure is described for measuring the degree of precipitation that occurs when a solubilized drug is injected. This in vitro technique was used to show that alprazolam injection shows less precipitation than diazepam injection under all tested conditions, and that the precipitation observed with diazepam can be controlled by ensuring that the formulation is injected very slowly. This simple technique also can be used during preformulation development to evaluate the relative potential for precipitation of various formulations.

Alprazolam↗
PubMed1981

Solubility and partitioning IV: Aqueous solubility and octanol-water partition coefficients of liquid nonelectrolytes.

The aqueous solubility and octanol-water partition coefficient of over 100 nonelectrolyte organic liquid solutes are related by the simple equation log Sw = -1.016 log PC +0.515, where Sw is the molar solubility of liquid solutes in water and PC is the experimental partition coefficient of the solutes in the octanol-water system. The liquids studied represent a wide variety of organic compounds including aliphatic and aromatic hydrocarbons, alcohols, esters, ethers, aldehydes, and ketones. This finding is in agreement with that reported by Hansch and coworkers. However, these results are significant because only the experimental values for the aqueous solubilities and octanol-water partition coefficients are included, as opposed to the calculated partition coefficients used by Hansch. This relationship is extremely useful in understanding the overall solubility and partitioning phenomenon for organic liquids are provides a basis for studying crystalline solids and gases.

Chemical Phenomena↗