Transdermal drug delivery not only has contributed immensely to medical practice, but has enjoyed enormous interest in the field of cosmetic and pharmaceutical industries. Nevirapine, a non‐nucleoside reverse transcr...Transdermal drug delivery not only has contributed immensely to medical practice, but has enjoyed enormous interest in the field of cosmetic and pharmaceutical industries. Nevirapine, a non‐nucleoside reverse transcriptase inhibitor (NNRTI) is used clinically for the treatment of HIV‐ 1 infection. The aim of the present study is to investigate the influence of cosolvents (glycerol, propylene glycol, ethanol, polyethylene glycol 400) and surfactants (polysorbate 20, polysorbate 80, sodium lauryl sulfate, sodium cholate and cetrimide) on the dermal permeability coefficient of nevirapine by utilizing established and recognized mathematical model that employs partition coefficient as one of its molecular descriptors. The partition coefficient of nevirapine is determined in chloroform-water system at room temperature using the shake flask method. The results show that all the cosolvents used in this study decrease the partition coefficient of nevirapine. The same decrease in the partition coefficient of nevirapine is observed with all the surfactants investigated. The order of dermal enhancement potential of the vehicles studied based on the predicted permeability coefficient is glycerol > propylene glycol > ethanol > polyethylene glycol 400 for the cosolvents while tween 20 > tween 80 > sodium lauryl sulfate > sodium cholate > cetrimide for the surfactants. The maximum predicted flux through skin was obtained by multiplying the predicted permeability coefficient and the drug aqueous solubility. As the rate of penetration into the skin is quantitatively assessed by the use of permeability coefficient, the findings suggest that for dermal formulation of nevirapine, glycerol and tween 20 are the most preferred vehicles out of the vehicles investigated. Furthermore, the results of the correlation coefficients obtained by plotting permeability coefficient or maximum predicted flux, versus logarithm partition coefficient indicate that permeability coefficient can be a more reliable parameter to predict transdermal absorption of nevirapine than flux.展开更多
Transdermal delivery acts as an alternative to oral delivery of drugs and possibly provids also an alternative to hypodermic injection. Transdermal delivery when compared to oral route has a variety of advantages name...Transdermal delivery acts as an alternative to oral delivery of drugs and possibly provids also an alternative to hypodermic injection. Transdermal delivery when compared to oral route has a variety of advantages namely: avoiding the degradation of drugs in the stomach environment, providing steady plasma levels, avoiding first-pass metabolism, increaseing patient compliance, easy to use, non-invasive and inexpensive, increasing the therapeutic index with a simultaneous decrease in drug side effects. Despite these advantages, one of the greatest challenges to transdermal delivery is that only a limited number of drugs are amenable to administration by this route. Gemifloxacin, a broad spectrum fourth generation quinolone antibacterial agent has pharmacokinetic characteristics (particularly its low maximum plasma concentration, obtained following repeat oral dose of 320 mg) that makes it a potential target for transdermal delivery. The objective of the study was to explore the possibility of surfactants (anionic, cationic and nonionic) acting as dermal enhancers of gemifloxacin assuming that the drug is to be formulated into topical or transdermal pharmaceutical dosage form. To accomplish the objective, gemifloxacin was partitioned between chloroform and surfactants containing varying concentrations of sodium lauryl sulfate, cetyltrimethylammonium bromide, polysorbate-20 and polysorbate-80. The data obtained were used to estimate the dermal permeability coefficient. The partitioning was carried out by shake flask method at room temperature. It was observed that all the surfactants decreased the partition behavior of gemifloxacin when compared to that of water alone. Sodium lauryl sulfate produced the most decreasing partition effect at the highest concentration studied (2% w/v). The permeability coefficient (Kp) was estimated from the partition coefficient data and the molecular weight of the drug. As permeability coefficient is an important descriptor for evaluating dermal absorption of drugs employed in clinical treatment of various dermal accessible ailments, the results of the study suggest that the investigated surfactants might not be potential transdermal enhancers of gemifloxacin.展开更多
文摘Transdermal drug delivery not only has contributed immensely to medical practice, but has enjoyed enormous interest in the field of cosmetic and pharmaceutical industries. Nevirapine, a non‐nucleoside reverse transcriptase inhibitor (NNRTI) is used clinically for the treatment of HIV‐ 1 infection. The aim of the present study is to investigate the influence of cosolvents (glycerol, propylene glycol, ethanol, polyethylene glycol 400) and surfactants (polysorbate 20, polysorbate 80, sodium lauryl sulfate, sodium cholate and cetrimide) on the dermal permeability coefficient of nevirapine by utilizing established and recognized mathematical model that employs partition coefficient as one of its molecular descriptors. The partition coefficient of nevirapine is determined in chloroform-water system at room temperature using the shake flask method. The results show that all the cosolvents used in this study decrease the partition coefficient of nevirapine. The same decrease in the partition coefficient of nevirapine is observed with all the surfactants investigated. The order of dermal enhancement potential of the vehicles studied based on the predicted permeability coefficient is glycerol > propylene glycol > ethanol > polyethylene glycol 400 for the cosolvents while tween 20 > tween 80 > sodium lauryl sulfate > sodium cholate > cetrimide for the surfactants. The maximum predicted flux through skin was obtained by multiplying the predicted permeability coefficient and the drug aqueous solubility. As the rate of penetration into the skin is quantitatively assessed by the use of permeability coefficient, the findings suggest that for dermal formulation of nevirapine, glycerol and tween 20 are the most preferred vehicles out of the vehicles investigated. Furthermore, the results of the correlation coefficients obtained by plotting permeability coefficient or maximum predicted flux, versus logarithm partition coefficient indicate that permeability coefficient can be a more reliable parameter to predict transdermal absorption of nevirapine than flux.
文摘Transdermal delivery acts as an alternative to oral delivery of drugs and possibly provids also an alternative to hypodermic injection. Transdermal delivery when compared to oral route has a variety of advantages namely: avoiding the degradation of drugs in the stomach environment, providing steady plasma levels, avoiding first-pass metabolism, increaseing patient compliance, easy to use, non-invasive and inexpensive, increasing the therapeutic index with a simultaneous decrease in drug side effects. Despite these advantages, one of the greatest challenges to transdermal delivery is that only a limited number of drugs are amenable to administration by this route. Gemifloxacin, a broad spectrum fourth generation quinolone antibacterial agent has pharmacokinetic characteristics (particularly its low maximum plasma concentration, obtained following repeat oral dose of 320 mg) that makes it a potential target for transdermal delivery. The objective of the study was to explore the possibility of surfactants (anionic, cationic and nonionic) acting as dermal enhancers of gemifloxacin assuming that the drug is to be formulated into topical or transdermal pharmaceutical dosage form. To accomplish the objective, gemifloxacin was partitioned between chloroform and surfactants containing varying concentrations of sodium lauryl sulfate, cetyltrimethylammonium bromide, polysorbate-20 and polysorbate-80. The data obtained were used to estimate the dermal permeability coefficient. The partitioning was carried out by shake flask method at room temperature. It was observed that all the surfactants decreased the partition behavior of gemifloxacin when compared to that of water alone. Sodium lauryl sulfate produced the most decreasing partition effect at the highest concentration studied (2% w/v). The permeability coefficient (Kp) was estimated from the partition coefficient data and the molecular weight of the drug. As permeability coefficient is an important descriptor for evaluating dermal absorption of drugs employed in clinical treatment of various dermal accessible ailments, the results of the study suggest that the investigated surfactants might not be potential transdermal enhancers of gemifloxacin.
