Loratadine is a long acting tricyclic antihistamine with selective peripheral histamine H1-receptor antagonist activity that is used for relief of symptoms of seasonal allergies and skin rash. In case of oral administration of antihistamines, it may cause many adverse effects such as headache, fatig...
Loratadine is a long acting tricyclic antihistamine with selective peripheral histamine H1-receptor antagonist activity that is used for relief of symptoms of seasonal allergies and skin rash. In case of oral administration of antihistamines, it may cause many adverse effects such as headache, fatigue, and nausea due to transient high blood concentration. To avoid these side effects, loratadine could be administered using a transdermal drug delivery system (TDDS). Ethylene vinyl acetate (EVA) which is heat-processible, flexible, and inexpensive material has been used for the transdermal drug delivery. The study was carried out to evaluate the possibility of using the EVA polymer as a controlling membrane and further develop the EVA matrix system for transdermal delivery of loratadine. The EVA matrix containing loratadine was fabricated by casting method and the release patterns were observed. The solubility of loratadine according to the volume fraction of polyethylene glycol (PEG) 400 was determined and the permeation of drug through the EVA membrane with various volume fraction of PEG 400 was studied using the two chamber-diffusion cell. The effects of drug concentration, temperature, and plasticizers on drug release were determined using the modified Keshary-Chien cell. The release of drug from the matrix was studied as a function of temperature and drug concentration. Some kinds of plasticizers such as the citrates and the phthalates were used for preparing the pore of EVA matrix and increasing the flexibility of EVA matrix. The release study from the EVA matrix was performed at 37℃ using 40% PEG 400 as a receptor medium. To increase the skin permeation of loratadine from the EVA matrix, various enhancers were added to the EVA matrix containing 4% loratadine. The enhancing effects of the enhancers on the skin permeation of loratadine were evaluated using the modified Keshary-Chien cell fitted with the intact excised rat skin. Enhancers such as the saturated, the unsaturated fatty acids, the pyrrolidones, the propylene glycol derivatives, the glycerides, and the non-ionic surfactants were used. The effectiveness of penetration enhancers, the ratio of loratadine flux in the presence or absence of enhancers, was defined as the enhancement factor (EF). The membrane structure were examined by scanning electron microscope (SEM). The antihistamine effects of loratadine-EVA matrix containing the enhancer and plasticizer by transdermal administration were studied by detecting the vascular permeability in rats. The changes in vascular permeability following the transdermal delivery were determined by the evans blue dye method. The solubility test according to the PEG 400 volume fraction showed the best solubility at 40% PEG 400 solution. The release rate of drug from the EVA matrix increased with increased temperature and drug loading doses. The activation energy(Ea), which was measured from slope of logP versus 1000/T plots was 6.830 kcal/mol for 1% loading dose, 6.803 kcal/mol for 2% loading dose, and 6.770 kcal/mol for 3% loading dose, 6.711 kcal/mol for 4% loading dose, 6.652 kcal/mol for 5% loading dose from EVA matrix. A linear relationship existed between the release rate and the square root of loading dose. Among the plasticizers used such as the citrates and the phthalates groups, diethyl phthalate (DEP) showed the best effect on the release of loratadine. Among the enhancers used such as the propylene glycol derivatives, the fatty acids, and the non-ionic surfactants, the pyrrolidones, N-methyl-2-pyrrolidone(NMP) showed the best enhancement effect (EF : 4.11). The vascular permeability was inhibited about 20.335 % from the transdermal loratadine-EVA matrix comparing with the control. An inhibition (33.961 %) was shown from the transdermal loratadine-EVA matrix containing DEP and NMP. The surface morphology determined by scanning electron microscopy showed that the drug was released through the microchannel produced by the plasticizer from the loratadine-EVA matrix containing the plasticizer. In conclusion, the enhanced transdermal delivery of loratadine, the application of the EVA matrix containing plasticizer and permeation enhancer could be useful in the development of transdermal drug delivery system.
Loratadine is a long acting tricyclic antihistamine with selective peripheral histamine H1-receptor antagonist activity that is used for relief of symptoms of seasonal allergies and skin rash. In case of oral administration of antihistamines, it may cause many adverse effects such as headache, fatigue, and nausea due to transient high blood concentration. To avoid these side effects, loratadine could be administered using a transdermal drug delivery system (TDDS). Ethylene vinyl acetate (EVA) which is heat-processible, flexible, and inexpensive material has been used for the transdermal drug delivery. The study was carried out to evaluate the possibility of using the EVA polymer as a controlling membrane and further develop the EVA matrix system for transdermal delivery of loratadine. The EVA matrix containing loratadine was fabricated by casting method and the release patterns were observed. The solubility of loratadine according to the volume fraction of polyethylene glycol (PEG) 400 was determined and the permeation of drug through the EVA membrane with various volume fraction of PEG 400 was studied using the two chamber-diffusion cell. The effects of drug concentration, temperature, and plasticizers on drug release were determined using the modified Keshary-Chien cell. The release of drug from the matrix was studied as a function of temperature and drug concentration. Some kinds of plasticizers such as the citrates and the phthalates were used for preparing the pore of EVA matrix and increasing the flexibility of EVA matrix. The release study from the EVA matrix was performed at 37℃ using 40% PEG 400 as a receptor medium. To increase the skin permeation of loratadine from the EVA matrix, various enhancers were added to the EVA matrix containing 4% loratadine. The enhancing effects of the enhancers on the skin permeation of loratadine were evaluated using the modified Keshary-Chien cell fitted with the intact excised rat skin. Enhancers such as the saturated, the unsaturated fatty acids, the pyrrolidones, the propylene glycol derivatives, the glycerides, and the non-ionic surfactants were used. The effectiveness of penetration enhancers, the ratio of loratadine flux in the presence or absence of enhancers, was defined as the enhancement factor (EF). The membrane structure were examined by scanning electron microscope (SEM). The antihistamine effects of loratadine-EVA matrix containing the enhancer and plasticizer by transdermal administration were studied by detecting the vascular permeability in rats. The changes in vascular permeability following the transdermal delivery were determined by the evans blue dye method. The solubility test according to the PEG 400 volume fraction showed the best solubility at 40% PEG 400 solution. The release rate of drug from the EVA matrix increased with increased temperature and drug loading doses. The activation energy(Ea), which was measured from slope of logP versus 1000/T plots was 6.830 kcal/mol for 1% loading dose, 6.803 kcal/mol for 2% loading dose, and 6.770 kcal/mol for 3% loading dose, 6.711 kcal/mol for 4% loading dose, 6.652 kcal/mol for 5% loading dose from EVA matrix. A linear relationship existed between the release rate and the square root of loading dose. Among the plasticizers used such as the citrates and the phthalates groups, diethyl phthalate (DEP) showed the best effect on the release of loratadine. Among the enhancers used such as the propylene glycol derivatives, the fatty acids, and the non-ionic surfactants, the pyrrolidones, N-methyl-2-pyrrolidone(NMP) showed the best enhancement effect (EF : 4.11). The vascular permeability was inhibited about 20.335 % from the transdermal loratadine-EVA matrix comparing with the control. An inhibition (33.961 %) was shown from the transdermal loratadine-EVA matrix containing DEP and NMP. The surface morphology determined by scanning electron microscopy showed that the drug was released through the microchannel produced by the plasticizer from the loratadine-EVA matrix containing the plasticizer. In conclusion, the enhanced transdermal delivery of loratadine, the application of the EVA matrix containing plasticizer and permeation enhancer could be useful in the development of transdermal drug delivery system.
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