Effect of pH on weakly acidic and basic model drugs and determination of their ex vivo transdermal permeation routes

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

Towards a Correlation between Polar Surface Area of Drugs with Ex-vivo Transdermal Flux Variability

Abstract The aim of the present study was to investigate the relationship between the polar surface area and other molecular properties of the model drugs and their transdermal permeability across the rat skin. Few model drugs which are weakly acidic (ibuprofen, aceclofenac and glipizide) and weakly basic (olanzapine, telmisartan and sildenafil citrate) were selected for the study based on Polar surface area (PSA). Ex-vivo studies were carried out in franz diffusion cell. The skin permeation parameters of the model drugs were correlated to the physicochemical properties. The physicochemical properties considered for the study have shown to be synonymous with the pre-established ideal properties for the transdermal permeation. In acidic drugs, the order of correlation of the physicochemical properties to flux was mol. wt. > total no. of hydrogen bonds > M.P > PSA > Log P > Log D > solubility. In basic drugs, the order of correlation of the physicochemical properties to flux was mol. wt > PSA > solubility > log P > log D> total no. of hydrogen bonds> M.P. The property considered for the study PSA has acquired 4 th rank in acidic drugs with R 2 = 0.9465 and 2 nd in basic drugs with R 2 = 0.9477. The prime important factor for the study PSA, has shown a tortuous effect on the permeation of the selected drugs, whereas further study of PSA in relation to skin permeability parameters by considering larger drug data sets may impart a clearer image of its influence on transdermal permeation

Towards a Correlation between Polar Surface Area of Drugs with Ex-vivo Transdermal Flux Variability: Polar Surface Area and transdermal permeability

The aim of the present study was to investigate the relationship between the polar surface area and other molecular properties of the model drugs and their transdermal permeability across the rat skin. Few model drugs which are weakly acidic (ibuprofen, aceclofenac and glipizide) and weakly basic (olanzapine, telmisartan and sildenafil citrate) were selected for the study based on Polar surface area (PSA). Ex- vivo studies were carried out in franz diffusion cell. The skin permeation parameters of the model drugs were correlated to the physicochemical properties. The physicochemical properties considered for the study have shown to be synonymous with the pre-established ideal properties for the transdermal permeation. In acidic drugs, the order of correlation of the physicochemical properties to flux was mol. wt. > total no. of hydrogen bonds > M.P > PSA > Log P > Log D > solubility. In basic drugs, the order of correlation of the physicochemical properties to flux was mol. wt > PSA > solubility > log P > log D> total no. of hydrogen bonds> M.P. The property considered for the study PSA has acquired 4th rank in acidic drugs with R2= 0.9465 and 2nd in basic drugs with R2= 0.9477. The prime important factor for the study PSA, has shown a tortuous effect on the permeation of the selected drugs, whereas further study of PSA in relation to skin permeability parameters by considering larger drug data sets may impart a clearer image of its influence on transdermal permeation

Effect of pH on weakly acidic and basic model drugs and determination of their ex vivo transdermal permeation routes

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