Abstract
ABSTRACT The aim of the present study was to investigate the effect of donor pH on the transdermal permeability of the model drugs across rat skin and also to determine the major route of transport of the drugs. Weakly acidic drugs (partition coefficient) ibuprofen (3.6), aceclofenac (3.9), glipizide (1.9) and weakly basic drugs olanzapine (3.6), telmisartan (6.0), and sildenafil citrate (1.9) were selected for the study. The ex vivo permeation studies of these drugs at different donor pH (pH - 1.2, 4, 5, 6.8, 7.4, and 8) using Franz diffusion cell (area, 7.54 cm2) has shown a pH-dependent permeability. Among these drugs the weakly acidic drugs has shown higher permeation rates compared to the weakly basic drugs. The permeability coefficient and the distribution coefficient of the weakly basic drugs increased on increasing the pH whereas the weakly acidic drugs showed an inverse relation. The weakly basic drugs also showed an increase in permeation with increase in the fraction of unionized species indicating dominance of transcellular route of permeation. With an exception of sildenafil citrate, a weakly basic salt form of the drug which showed a high permeation value at pH 7.4 where 57% of the drug was unionized, indicating the involvement of both paracellular and transcellular route in its permeation.
Highlights
Skin, the largest organ of the body offers a large surface area along with pervasive circulatory and lymphatic network making it the preferred noninvasive route of drug delivery
Increase in the amount of nonionised drug may lead to enhanced permeability, which can be attained by a change in pH of the drug delivery system
The aim of the present study was to investigate the effect of pH and ionization on permeation and to understand in vitro transport across rat skin based on varying pH using weakly acidic drugs ibuprofen, aceclofenac, and glipizide and weakly basic drugs olanzapine, telmisartan, and sildenafil citrate as model drugs
Summary
The largest organ of the body offers a large surface area along with pervasive circulatory and lymphatic network making it the preferred noninvasive route of drug delivery. Delivery of a drug through the skin for local or systemic pharmacological effect has been an assuring concept since a long time. It is noted that pH has an effect on the permeation of drugs through biological membranes such as oral mucosa, intestinal membrane etc., affecting the route of permeation. Implicating the importance of examining the effect of pH on transdermal drug delivery that determines the penetration route, which is an intrinsic factor for the selection of penetration enhancer to improve the drug permeability. General absorption of ionizable drugs across gastrointestinal tract has been explained. It is assumed that penetration of the drug through dermis is influenced by its ionic condition and ionized species are known to permeate poorly compared to nonionized species (Hadgraft, Valenta, 2000). Increase in the amount of nonionised drug may lead to enhanced permeability, which can be attained by a change in pH of the drug delivery system
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