RESUMEN
The development of a transdermal delivery system for isosorbide dinitrate (ISDN) using electron beam irradiation was studied. The solid state stability of the drug to irradiation was assessed. The drug was dissolved in 2-ethylhexylacrylate (EHA)-acrylic acid (AA) system and this solution was directly irradiated on a backing membrane (Scotchpak1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratios (EWSR), differential scanning calorimetry (DSC), weight uniformity, thickness uniformity, drug content and content uniformity, peel strength, in vitro release, skin permeation kinetics and skin irritation potential. The developed system possessed excellent adhesive properties. Increase in the irradiation doses did not have a significant effect on the peel strength values. The systems exhibited promising skin permeation kinetics and no skin irritating potential, both of which are important properties for transdermal drug delivery. The ISDN-EHA-AA system developed at an irradiation dose of 50 kGy showed a higher skin permeation profile as compared to an internationally marketed transdermal matrix system of ISDN.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Dinitrato de Isosorbide/administración & dosificación , Dinitrato de Isosorbide/efectos de la radiación , Administración Cutánea , Animales , Rastreo Diferencial de Calorimetría , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Femenino , Técnicas In Vitro , Dinitrato de Isosorbide/farmacocinética , Permeabilidad , Conejos , Piel/metabolismo , Solubilidad , Temperatura , Factores de TiempoRESUMEN
A transdermal steroidal delivery system usually contains a high concentration of drug to obtain high drug fluxes. The present investigation involved the development of drug-in-adhesive transdermal systems of estradiol using synthesized acrylate copolymer (EA) of 2-ethylhexyl acrylate and acrylic acid. The effect of several variables such as varying drug polymer ratios, effect of Eudragit RL PO and Eudragit E PO and effect of drying temperatures on prevention of drug crystallization in the formulation matrix was investigated. The systems free from drug crystals were evaluated and compared with a marketed formulation with respect to its skin permeation profile. The optimized formulation was also subjected to accelerated stability testing. Eudragit RL PO and Eudragit E PO were found to be effective as crystallization inhibitors in the transdermal matrix systems tested. Formulations fabricated with Eudragit E PO gave transparent systems with good film properties and a higher skin permeation profile as compared to that of the marketed system. Higher temperature and humidity conditions facilitated the formation of drug crystals, whereas no crystals were observed in the formulation matrix at 23+/-0.5 degrees C and at 30+/-1 degrees C for the period of 6 months studied.
Asunto(s)
Adhesivos/farmacocinética , Estradiol/farmacocinética , Ácidos Polimetacrílicos/farmacocinética , Adhesivos/administración & dosificación , Adhesivos/química , Administración Cutánea , Animales , Cristalización , Sistemas de Liberación de Medicamentos , Almacenaje de Medicamentos/métodos , Estradiol/administración & dosificación , Estradiol/química , Cobayas , Ácidos Polimetacrílicos/administración & dosificación , Ácidos Polimetacrílicos/química , Absorción Cutánea/efectos de los fármacos , Absorción Cutánea/fisiologíaRESUMEN
Estradiol (ESD) is widely used in post climacteric replacement therapy. Most of the methods used for quantitation are expensive and time consuming. A rapid, selective and precise stability indicating high performance thin layer chromatography method was developed and validated for the estimation of ESD in bulk and pharmaceutical dosage forms. The method employed TLC aluminium plate precoated with silica gel 60F254 as the stationary phase. The solvent system employed consisted of chloroform-acetone-isopropyl alcohol-glacial acetic acid (9:1:0.4:0.1, v/v/v/v). Such a complex system was essential to obtain a dense and compact spot of the drug at an Rf value of 0.40 +/- 0.02. The drug on intentional degradation gave two products with Rf values of 0.52 +/- 0.01 and 0.58 +/- 0.01 respectively. Spectrodensitometric scanning-integration was performed on a Camag system using a wavelength of 286 nm. The polynomial regression data for the calibration plots exhibited good linear relationship (r = 0.9947) over a concentration range of 1-8 microg. Recovery studies were also performed at three experimental levels. The recovery data reveals that the RSD for intra-day and inter-day analysis was found to be 1.27% and 1.75%, respectively. The proposed method was found to be stability indicating. Statistical analysis proves that the method is precise, accurate and reproducible, hence can be employed for the routine analysis of the drug.