Liposome formulation of NSC-639829 using halothane as a solvent: a technical note.
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Antineoplastic Agents↗
Biomedical subjects
Samuel H Yalkowsky
Publications and source records attributed to Samuel H Yalkowsky.
Solubilization of Fluasterone in cosolvent/cyclodextrin combinations.
The combined effect of cosolvent (methanol (MeOH), ethanol (EtOH), or n-propanol (n-PrOH)) and complexant hydroxypropyl-beta-cyclodextrin (HP beta CD) on the solubility of Fluasterone is evaluated and explained with a simple equation. The calculated constants in the equation not only quantitatively describe the dependence of drug solubility on cosolvent and ligand concentrations, but also explain the minima that are observed in the Fluasterone solubility versus cosolvent concentration curves at fixed HP beta CD concentrations.
1-Propanol↗
Prediction of Setschenow constants.
The Setschenow (salting out) constant by sodium chloride is related to molar volume, aqueous solubility, and octanol-water partition coefficient, K(ow), of the drug solute. This study validates a previously proposed relationship between the salting out constant of a solute and its partition coefficient. It also shows that the partition coefficient is a better descriptor of salting out than either molar volume or solubility.
Chemical Phenomena↗
Prediction of precipitation-induced phlebitis: a statistical validation of an in vitro model.
To avoid phlebitis, new intravenous (IV) parenterals are often screened by injection into animals. This method is not only expensive and time consuming, it is also detrimental to the animals. An alternate method, focusing on precipitation as the cause, uses an in vitro dynamic injection model that requires less money and time and reduces the need for live models. Validation of the dynamic injection apparatus, for predicting mechanical phlebitis, is established. Twenty-one currently marketed IV products were injected into isotonic Sorenson's phosphate buffer flowing at 5 mL/min. The resulting opacities, produced by precipitation, are measured in an ultraviolet flow cell. These opacity data, coupled with literature reports on phlebitis occurrence, were used to generate a logistic regression that indicates the probability of phlebitis given an opacity value measured by the apparatus. Regression results are supported by a receiver operator characteristic curve that establishes the most ideal cut-off opacity value. This opacity value provides the highest combined sensitivity (statistical power) and specificity while minimizing false-positive and false-negative results. Both analyses show that an opacity value of 0.003 best delineates phlebitic and nonphlebitic products. Measures of sensitivity (0.83), specificity (0.93), positive predictive value (0.93), and negative predictive value (0.78) indicate the model's predictive accuracy and reliability. These results support the use of the dynamic model in place of animals for preliminary phlebitis testing of new IV injectables.
Chemical Precipitation↗
Halothane, a novel solvent for the preparation of liposomes containing 2-4'-amino-3'-methylphenyl benzothiazole (AMPB), an anticancer drug: a technical note.
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Aniline Compounds↗
Stabilization and preformulation of anticancer drug--SarCNU.
The stability of SarCNU (NSC364432), 1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea in several pharmaceutically acceptable solvents was investigated by high pressure liquid chromatography (HPLC). The influences of light, ionic strength, pH, buffer concentration, and the following excipients: benzyl alcohol, ascorbic acid, sodium bisulfite, and disodium EDTA were studied at room temperature. The stability of the drug was also determined in water, EtOH, PG, Capmul PG, DMSO, and in different combinations of these cosolvents at four different temperatures. The degradation of the drug, which is catalyzed not only by general but also by specific acid and base, follows first order kinetics. Antioxidants, EDTA, and light have no effect on the degradation rate, suggesting oxidation is not a major degradation pathway. The t(90) in pure cosolvent is 25-50 times higher than that in water or semi-aqueous vehicles. Neat EtOH can be used to store the drug in a nonaqueous concentrate that is diluted with aqueous solvent prior to injection.
Antineoplastic Agents↗
Review on the systemic delivery of insulin via the ocular route.
Systemic drug absorption from the ocular route is well known. Although there is some absorption from the conjunctival sac, the nasal meatus is the site where the majority of systemic absorption of instilled drug takes place. This article reviews the principles of systemic absorption of insulin applied topically to the eye. The physiological and pharmaceutical considerations for formulation development and the strategy of improving the systemic absorption and bioavailability of insulin are also discussed.
Administration, Topical↗
Prediction of the aqueous solubility: comparison of the general solubility equation and the method using an amended solvation energy relationship.
An Amended Solvation Energy Relationship (ASER) was recently reported to successfully predict the aqueous solubilities of a set of 664 organic compounds. The average absolute error and root mean square error are 0.43 and 0.62 log units, respectively. When the General Solubility Equation (GSE) is applied to the same set of compounds, it gives an average absolute error of 0.45 log units and a root mean square error of 0.62 log units. These results are similar to those of the ASER method. The advantages and disadvantages of each method are discussed. It is shown that when the two methods agree with each other, they also agree with the experimentally determined values.
Forecasting↗
Estimation of aqueous solubility of organic compounds by using the general solubility equation.
The general solubility equation (GSE) proposed by Jain and Yalkowsky was used to estimate aqueous solubility of 1026 non-electrolytes. The only parameters used in the GSE are melting points (MP) and octanol-water partition coefficients (Kow). No fitted parameters and no training set are employed in the GSE. The experimental solubility values were taken from the AQUASOL dATAbASE. The average absolute error and the root-mean-square error in the solubility estimates are 0.38 and 0.53 log units, respectively. Thus, with an observed MP and calculated Kow; the users can obtain a reasonable estimation of the aqueous solubility of any organic non-electrolyte.
Forecasting↗
Independence of the product of solubility and distribution coefficient of pH.
PURPOSE: The relationship between the pH, solubility, and partition coefficient was investigated to show that the product of intrinsic values of solubility and partition coefficient is equal to the product of total values of solubility and distribution coefficient at different pH. METHODS: The pH distribution profiles were obtained from the literature and the pH solubility profiles were obtained from the literature or calculated from their intrinsic solubility and pK(a). RESULTS: The pH solubility and pH distribution coefficient profiles of 25 compounds were investigated to show that the product of intrinsic solubility (S(w)) and intrinsic octanol-water partition coefficient (K(ow)) is equal to the product of total solubility of a partially ionized solute (ST) and its octanol-buffer distribution coefficient (K(D)) at any pH where ion pair formation and salt precipitation are not present. CONCLUSIONS: The fact that S(w) x K(ow) can be used instead of S(T) x K(D) to model the absorption of partially ionized drugs in the gastrointestinal tract has important biopharmaceutical implications.
Hydrogen-Ion Concentration↗