Permeability drug formulation

BCS Class IV Low-solubility, low-permeability drugs. These compounds have very poor oral bioavailability. They are not only difficult to dissolve but often exhibit limited permeability across the GI mucosa. These drugs tend to be very difficult to formulate and can exhibit very large intersubject and intrasubject variability. 

Motz SA, Schaefer UF, Balbach S, Eichinger T, Lehr CM (2006) Permeability assessment for solid oral drug formulations based on Caco-2 monolayer in combination with a flow through dissolution cell. Eur J Pharm Biopharm 66 (2) 286-295... 

Although the potential to use Caco-2 cells to screen large numbers of formulations under carefully controlled experimental conditions appears attractive, the assumption that this model is suitable to evaluate drug formulations should not be made. In fact, the utility of Caco-2 cells in formulation evaluation is limited because these cells are sensitive to pharmaceutical excipients.112 In addition, the dilution of formulations into the simple buffer solutions used in permeability studies is likely to break the physical integrity of the... 

Membrane permeability is one of the most important determinants of pharmacokinetics, not only for oral absorption, but also for renal re-absorption, biliary excretion, skin permeation, distribution to a specific organ and so on. In addition, modification of membrane permeability by formulation is rarely successful. Therefore, membrane permeability should be optimized during the structure optimization process in drug discovery. In this chapter, we give an overview of the physiology and chemistry of the membranes, in vitro permeability models and in silica predictions. This chapter focuses on progress in recent years in intestinal and blood-brain barrier (BBB) membrane permeation. There are a number of useful reviews summarizing earlier work [1-5]. 

Sanderson J, deReil S, Dixon R. Iontophoretic delivery of nonpeptide drugs formulation optimization for maximum skin permeability. J Pharm Sci 1989 78 361-364. 

The partition coefficient, which will be described in more detail later in this chapter, is the relative solubility of the compound in lipid and water, and the compound s solubility really reflects the ability of the toxicant to move from a relatively aqueous environment across a lipid membrane. It is this factor that is often manipulated in pesticide and drug formulations to create a vehicle. Membrane permeability is therefore strongly correlated to the lipid solubility of the toxicant in the membrane as well as... 

Apart from the effects already discussed, the fundamental conclusion of our work is that synthetic and natural surfactants behave in different ways. When these kinds of additives are used in a drug formulation their possible influence on drug permeability and absorption must be considered. 

Bile salts, which are surface active, promote dissolution of lipophilic drugs and lipophilic drug formulations, enteric coatings, and waxy drug matrices. Bile salts may also promote membrane permeability of lipophilic molecules through micelle formation and solubilization. 

The present summary will cover only those technologies where the drug formulation itself is used to penetrate the skin via its mechanical energy. It will not describe any technology where a needle is used to puncture the skin, even if the needle is not visible to the patient or only the epidermis is punctured, such as mini-needles, microneedles, pen injectors, or autoinjectors. Also excluded are systems that ablate the skin mechanically or otherwise disrupt its chemical or mechanical structure to increase its permeability, such as laser ablation, microdermal ablation, electroporation, or iontophoresis. These are usually referred to as transdermal drug delivery, but can also be described as needle free. 

Sanderson, J.E. Reil, S.D. Dixon, R. Iontophoretic delivery of non-peptide drugs formulation optimization from maximum skin permeability. J. Pharm. Sci. 1989, 78,361-364. 

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