Solubility lipophilicity

Compare and contrast the electrostatic potential map of a typical detergent with that of a typical soap (stearate). Which part of each molecule will be most water soluble (hydrophilic) Draw a Lewis structure that describes each molecule s water-soluble group (make sure you indicate all necessary formal charges and lone pairs). Which part(s) of each molecule will be most grease soluble (lipophilic) What kinds of atoms and bonds are found in these groups ... 

Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

The coverage of permeability in this book is more comprehensive than that of solubility, lipophilicity, and ionization. This decision was made because permeability is not as thoroughly treated in the pharmaceutical literature as the other topics, and also because much emphasis is placed on the PAMPA in this book, which is indeed a very new technique [547] in need of elaboration. 

Catalysis in Transacylation Reactions. The principal objective of the study was to evaluate 4 as an effective organic soluble lipophilic catalyst for transacylation reactions of carboxylic and phosphoric acid derivatives in aqueous and two-phase aqueous-organic solvent media. Indeed 4 catalyzes the conversion of benzoyl chloride to benzoic anhydride in well-stirred suspensions of CH2CI2 and 1.0 M aqueous NaHCC>3 (Equations 1-3). The results are summarized in Table 1 where yields of isolated acid, anhydride and recovered acid chloride are reported. The reaction is believed to involve formation of the poly(benzoyloxypyridinium) ion intermediate (5) in the organic phase (Equation 1) and 5 then quickly reacts with bicarbonate ion and/or hydroxide ion at the interphase to form benzoate ion (Equation 2 and 3). Apparently most of the benzoate ion is trapped by additional 5 in the organic layer or at the interphase to produce benzoic anhydride (Equation 4), an example of normal phase-... 

As most drugs are preferably given orally, absorption which is complete, consistent and predictable is desirable. Although it may be possible from solubility, lipophilicity, pKa, molecular size, and animal data to make some prediction about likely absorption, only a study in humans will give quantitative data as the mechanisms of drug absorption are complex and still incompletely understood (Washington et al., 2001). It may be helpful here to distinguish between the terms absorption and bioavailability. ... 

S. G. Kerr, T. I. Kalman, Highly Water-Soluble Lipophilic Prodrugs of the Anti-HIV Nucleoside Analogue 2, 3 -Dideoxycytidine and Its 3 -Fluoro Derivative , J. Med. Chem. 1992, 35, 1996 - 2001 S. G. Kerr, T. I. Kalman, V4-(Dialkylaminomelhylcnc Derivatives of 2 -Deoxycytidine and Arabinocytidine Physicochemical Studies for Potential Prodrug Applications , J. Pharm. Sci. 1994, 83, 582 - 586. 

Bioavailability can be assessed early in the discovery process by combining data from a number of independent in vitro assays run as part of a pharmaceutical properties profile. These assays generally include some measurement of aqueous solubility, lipophilicity, cell or membrane permeability, and metabolic stability. In most cases, proper interpretation of... 

Hormones are divided into two major categories, those that are water soluble (hydrophilic) and those that are lipid soluble (lipophilic, also known as hydrophobic). Important properties of these two classes are shown in Table 1-9-1,... 

Each hormone is the center of a hormonal regulation system. Specialized glandular cells synthesize the hormone from precursors, store it in many cases, and release it into the bloodstream when needed (biosynthesis). For transport, the poorly water-soluble lipophilic hormones are bound to plasma proteins known as hormone carriers. To stop the effects of the hormone again, it is inactivated by enzymatic reactions, most of which take place in the liver (metabolism). Finally, the hormone and its metabolites are expelled via the excretory system, usually in the kidney (excretion). All of these processes affect the concentration of the hormone and thus contribute to regulation of the hormonal signal. 

Knowledge ofthe aqueous ionization constant,pof an ionizable drug candidate is very important because it can be used to predict solubility, lipophilicity, and permeability at different pH therefore, it... 

Kerr, S. G. andT. I. Kalman. 1992. Highly water-soluble lipophilic prodrugs of the anti-HIV nucleoside analogue 2/,3/-dideoxycytidine and its 3 uoro derivativeJ. Med. Chem35 1996-2001. 

Schamp, K., Schreder, S.A., and Dressman, J., Developmentrofr4mD/in vivo correlation for lipid formulations of EMD 50733, a poorly soluble, lipophilic drug substaiEoff, J. Pharm. Biopharm.,... 

The physicochemical properties of the drug molecules and the formulation can also influence rectal drug absorption (Table 7.1). Crucial parameters in this regard include drug concentration, molecular weight, solubility, lipophilicity, pKa, surface properties, and particle size [12]. In addition, formulation properties such as the nature of the suppository base material may play a critical role in regulating drug absorption. 

Scientists at Bayer implemented traffic lights for the prioritization of molecules from the HTS hits. Their score is based on solubility, lipophilicity, molecular weight, Polar Surface Area (PSA), and number of rotatable bonds. 

Xenobiotics may be present in water-soluble (hydrophilic) or in fat-soluble (lipophilic) form. However, they are also taken up in the body as gaseous substances and corpuscular-insoluble substrates (e. g. heavy metals). Any... 

The solubilizing capacity of micelles and microemulsions prepared using the surfactant N,N-dimethyl-dodecylamine-N-oxide (C12AO), and containing either one of two semipolar ethyl ester oils (i.e., EH or EO) for the poorly water soluble, lipophilic steroidal drug, testosterone enanthate, has been determined recently (Barlow, D.J. Lawrence, M.J. Zuberi, T. Zuberi, S. Heenan, R.K. Personal communication, 2005). 

Sterile parenteral oil-in-water emulsions have been used extensively for over 40 years for the intravenous administration of fats, carbohydrates, and vitamins to debilitated patients. Several vegetable oil-in-water emulsions are now available commercially with droplet sizes similar to that of chylomicrons (approximately 0.5-2 pm), the natural fat droplets in the blood that transport ingested fats to the lymphatic and circulatory systems (Table 1). More recently, such emulsions have been employed as intravenous carriers for poorly water-soluble lipophilic drugs such as vitamin K (e.g.. Sterile Phytonadione Injection U.S.P.) diazepam... 

Cyclosporin A is a sparingly water-soluble lipophilic cyclic peptide with a molecular weight of 1201 Da used in preventing rejection of transplanted kidneys, livers, and hearts, and is commercially available in multiple... 

Conversely, when dealing with solubilities, lipophilicity, or other properties of a set of different solutes in a specific solvent, the general equation is explicitly on the solute parameters ... 

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