Aqueous drug

Bevan, C. D., Uoyd, R. S. A high-throughput screening method for the determination of aqueous drug solubility using laser nephelometry in microtiter plates. Anal. Chem. 2000, 72,1781-1787. 

Bergstrom, C. A. S. Computational models to predict aqueous drug solubility, permeability and intestinal absorption. Exp. Opin. Drug Metab. Toxicol. 2005, 1, 513-527. 

Bergstrom, C. A. S. D., Norinder, U., Luthman, K., Artursson, P. Experimental and computational screening models for prediction of aqueous drug solubility. Pharm. Res. 2002, 19,182-188. 

It is not only the solid state of a drug that suffers from ambiguities, but also the aqueous state. The state relevant for the intrinsic solubility is the state of the saturated solution of the neutral species. Since most aqueous drug solubilities are small, direct interactions of the drug molecules are usually rare. Hence, this state is usually very similar to the state of the drug at infinite dilution in water. Most computational methods disregard saturation effects. Usually this is a good approximation, but one should keep in mind that this approximation may result in some moderate, but systematic errors at the upper end of the solubility scale. 

Fig. 15.1. Factors limiting oral drug absorption. Dissolution and the aqueous drug solubility in the gastrointestinal fluids are two of the properties influencing oral drug absorption. When the drug is in solution, it can be subjected to chemical degradation and complex binding with components of the gastrointestinal fluids and/or be metabolised by...

Onofrey, T. and Kazan, G. Performance and Correlation of a 96-Well High throughput Screening Method to Determine Aqueous Drug Solubility, Application Note (Billerica, MA Millipore Corp., 2003). 

The AERx pulmonary delivery system [40,41] can be regarded as a combination of a MDI and a nebulizer. This system forms an aerosol by extrusion of an aqueous drug-containing solution through a disposable nozzle containing an array of precisely micromachined holes. The droplets are entrained by the airflow passing over the blister. Control over the size distribution of the holes enables the formation of droplets having a narrow size distribution. 

Nevertheless, since almost all drug compounds are solid at ambient temperature, the calculation of aqueous drug solubility requires knowledge of the chemical potential, Acrystalline state. However, at present, there is no computational method available to reliably predict this chemical potential. Such prediction would involve knowledge about the crystal structure of the compound, which must... 

The rms deviation of this COSMO-RS drug-solubility prediction is 0.66 log-units on the training set. Considering the fact that the available data sets for aqueous drug solubility typically have an intrinsic experimented error of about 0.5 log-units (rms), this... 

Figure 3. Glass binding of ts -THC showing the percent of drug added that remained in solution at various times for (A) TMS-treated 50-mL volumetric flasks from an aqueous drug concentration of 0.1 ng/mL (B) an aqueous drug concentration of 0.1 ng/mL in untreated 50-mL volumetric flasks (C) an aqueous drug concentration of 0.1 ng/mL in water-soluble silicone concentrate-treated 50-mL volumetric flasks (D) an aqueous drug concentration of 0.05 pg/mL in untreated 50-mL volumetric flasks and (E) an aqueous drug concentration of 0.1 pg/mL in a 20-mL stainless steel ultracentrifuge tube. Each point is the mean of four separate determinations (1).

Although various computational approaches for the prediction of intestinal drug permeability and solubility have been reported [219], recent computer-based absorption models utilize a large number of topological, electronic, and geometric descriptors in an effort to take both aqueous drug solubility and permeability into account. Thus, descriptors of partitioned total surface areas [168], Abraham molecular descriptors [220,221], and a variety of structural descriptors in combination with neural networks [222] have been shown to be determinants of oral drug absorption. 

Three different types of inhalers are used to deliver drugs to the deep lung. Nebulizers, the oldest type of inhaler, work by producing a mist of aqueous, drug-containing droplets. The drug can be either dissolved or suspended in the water phase. In a pressurized metered dose inhaler (pMDI), the drug is... 

Bevan CD (2000) A High-throughput Screening Method for the Determination of Aqueous Drug Solubility Using Laser Nephelometry in Microtiter Plates. Anal Chem 72 1781-1787... 

The use of surfactants to modify the surface tension of an aerosol and alter its droplet size distribution has shown that their influence depends strongly on the characteristics of the solution to be aerosoled. The span, defined as 90% undersize —10% undersize/50% undersize, gives a measure of the width of the volume distribution relative to the median diameter of the droplets formed in the aerosoling process. Comparative studies performed with commercial air-jet and US nebulizers have shown that, under similar working conditions, the latter provide less heterodispersed aerosols, with span values ranging from 1.50 to 1.75, which are similar for aqueous drug solutions in the presence and absence of surfactants [156]. 

The key advantage of remote loading is that it leads to higher drug to Kpid ratios and encapsulation efficiencies compared to conventional passive trapping techniques like hydration of dried lipid films with aqueous drug solutions. 

Bergstrom CA, Luthman K, Artursson P. Accuracy of calculated pH-dependent aqueous drug solubility. Eur J Pharm Sci 2004 22 387-98. 

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