Drug properties absorption

In order to rationalize membrane permeability and oral absorption in terms of physicochemical drug properties, good experimental data and sound theoretical... 

Knowledge of drug properties, especially solubility in surfactants or as a function of pH, is essential. One could anticipate precipitation of the drug as the pH changes in solution, or if release from the dosage form leads to supersaturation of the test media. Be aware that preparation of a standard solution may be more difficult than expected. It is customary to use a small amount of alcohol to dissolve the standard completely. A history of the typical absorptivity range of the standard can be very useful to determine if the standard has been prepared properly. 

Drugs may be formulated as their salt forms (i.e., hydrochloride salt for base, sodium salts for acids) that dissociate in the body, or they may be formulated as the free acid or base. The fraction of the drug absorbed can be difficult to predict, as it is influenced by many factors. The extent and rate of absorption are partly determined by the physicochemical properties of the drug. Favorable absorption is related to lipid solubility, nonpolarity, and small molecular size. Reduced absorption is often observed for highly polar, non-lipid-soluble, and large-molecular size drugs. 

Together, the chemistry of codeine and the drug s absorption into the bloodstream, distribution to various compartments and tissues in the body, metabolism (breakdown of the parent compound into smaller molecules, or metabolites), and excretion are intimately related to how codeine exerts its medicinal or therapeutic effects. Codeine s chemical properties and pharmacologic characteristics explain how, figuratively speaking, a spoonful of codeine can relieve pain, suppress cough, or act as an antidiarrheal. 

Another way of describing the L T ratio concept is that of pulmonary targeting. Drug properties that improve pulmonary targeting include slow absorption from the lungs, low oral systemic availability, and rapid systemic clearance. 

The aims of this book are to highlight and summarize for medicinal and pharmaceutical chemists some important properties of phospholipid bilayers to explain, using examples, analytical tools for determining thermotropic and dynamic membrane properties and the possible effects of drugs on such membrane properties and, finally, to discuss examples of the importance of drag-membrane interactions for drug pharmacokinetics (absorption, distribution, accumulation) as well as drag efficacy, selectivity, and toxicity. 

Drug properties which affect vaginal drug delivery are broadly the same as those affecting transepithelial absorption at any site and have been discussed extensively in Chapter 1 (Section 1.3.4). 

Recommendations exist to conduct in vivo studies first in an animal species (preferably the pig) before going to man. This approach has limited validity because modified release is primarily defined by the absorption properties of a drug. As absorption is influenced by the general composition, the sums of the physicochemical properties, the length and residence times of each section of the GI tract, no animal species is... 

Novartis uses the In Silico Profiling web tool. Available properties include the octanol water partition coefficient log P, molar refractivity, flexibility index, hydrogen bonding characteristics and molecular polar surface area. Various drug properties, such as intestinal absorption, BBB permeability or Plasma Protein Binding (PPB) are calculated based on in-house models. 

Basic pharmacologic principles apply as much to drug interactions as to drug actions. Each kinetic property—absorption, distribution, metabolism (biotransformation), and excretion—is potentially affected by the presence of coadministered medications. Drug interactions follow a variable time-course pattern, from immediate to delayed. Consequently, it is important to remember that several weeks may elapse before the effects of an interactive combination are evident. 

Figure 3.1 The Biopharmaceutics Classification System as defined by Amidon et al. [6]. The BCS is a classification of drug substances according to their solubility and permeability properties, in orderto stand forthe most fundamental viewofthe drug intestinal absorption process following oral administration.

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