Diffusion transdermal

Active substances used in membrane diffusion transdermal systems can be the following steroid hormones, clonidine, scopolamine, nicotine, nitroglycerine, dexamethasone, propranolol, and analgesics (e.g. phentanyl, buprenor-phine), [60, 61, 75]. 

Skin. The skin s unique molecular transport and barrier properties pose a challenge for transdermal dmg dehvery. Diffusion of dmgs through the stratum corneum, the outer layer primarily responsible for the skin s limited permeabUity, varies by dmg, by skin site, and among individuals. Until recently, virtuaUy aU dmgs appHed to skin were topical treatments. 

Fig. 4. Schematic of transdermal therapeutic system in operation. The dmg diffuses through the intact skin into capillaries and is then carried into the...

Electrically assisted transdermal dmg deflvery, ie, electrotransport or iontophoresis, involves the three key transport processes of passive diffusion, electromigration, and electro osmosis. In passive diffusion, which plays a relatively small role in the transport of ionic compounds, the permeation rate of a compound is deterrnined by its diffusion coefficient and the concentration gradient. Electromigration is the transport of electrically charged ions in an electrical field, that is, the movement of anions and cations toward the anode and cathode, respectively. Electro osmosis is the volume flow of solvent through an electrically charged membrane or tissue in the presence of an appHed electrical field. As the solvent moves, it carries dissolved solutes. 

Hydration can be an important factor in diffusion and mass transport phenomena in pharmaceutical systems. It may alter the apparent solubility or dissolution rate of the drug, the hydrodynamic radii of permeants, the physicochemical state of the polymeric membrane through which the permeant is moving, or the skin permeability characteristics in transdermal applications. 

In many cases, transdermal drug absorption is investigated using a Franz-diffusion cell. The concentrations both in the membrane and the acceptor compartment are assumed to be zero at the start of the experiment. At different time points, the cumulative drug amount per unit area in the receptor q(t) is determined and plotted versus time t (Figure 20.1). After some time, the flux... 

Because most proteins are susceptible to protease degradation and denaturation in biologic fluids, most biopharmaceuticals must be administered by intravenous, intramuscular, or subcutaneous injection (see Table 5.5). High concentrations of proteases are found in the gastrointestinal tract, nasal mucosa, bronchioles, and alveoli, which severely limit the bioavailability of protein pharmaceuticals after oral, intranasal, and inhalation administration. Diffusional barriers to the passage of relatively large macromolecules preclude transdermal and mucosal administration of protein pharmaceuticals. Research is under way to develop methods that will protect protein drugs from proteolysis and improve transmembrane diffusion. 

Some pharmacokinetic properties of the commonly used amide local anesthetics are summarized in Table 26-2. The pharmacokinetics of the ester-based local anesthetics have not been extensively studied owing to their rapid breakdown in plasma (elimination half-life < 1 minute). Local anesthetics are usually administered by injection into dermis and soft tissues around nerves. Thus, absorption and distribution are not as important in controlling the onset of effect as in determining the rate of offset of local analgesia and the likelihood of CNS and cardiac toxicity. Topical application of local anesthetics (eg, transmucosal or transdermal) requires drug diffusion for both onset and offset of anesthetic effect. However, intracavitary (eg, intra-articular, intraperitoneal) administration is associated with a more rapid onset and shorter duration of local anesthetic effect. 

Franz diffusion cells (FDC) remain the workhorse of all permeation experiments in transdermal studies. FDCs use the permeation of a solute, assessed by high pressure liquid chromatography (HPLC) or radiation, to evaluate the effect of penetration... 

Iontophoresis by definition is the process of transport of ions into or through a tissue by the use of an applied potential difference across the tissue [52], Depending on the physicochemical characteristics of a molecular species, electrorepulsion is usually the primary mechanism of transdermal transport for ions, whereas electroosmosis and increased passive diffusion (as a result of the reduced barrier properties) are more prominent for neutral species [53]. In contrast, enhancement in flux for neutral or weakly charged species during electroporation arises predominantly from the reduced barrier properties of the membrane, whereas direct electrorepulsion is usually of secondary importance [25],... 

If skin is placed in a water bath under controlled conditions [14] the primary barrier to transdermal delivery, the epidermal membrane comprising the stratum corneum and viable epidermis, can be readily removed and used to analyze the penetration and diffusion of materials. Figure 18.3a and Figure 18.3b show the appearance of human breast epidermal membrane, with epidermis facing uppermost, following application of the cylindrical dry-etch and pyramidal wet-etch silicon microneedles, respectively. In each case the microneedles are clearly shown to pierce the stratum corneum and viable epidermis to facilitate controlled access of molecules to the target region of skin. 

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