Formulation Optimization and Study on Effect of Penetration Enhancers on Reservoir Transdermal Therapeutic Systems of Hydralazine Hydrochloride

Abstract

INTRODUCTIONPulmonary arterial hypertension is a progressive disease which is due to constriction of pulmonary artery by excessive production of endothelien receptors. Hydralazine hydrochloride (HZH) is a drug candidate used to treat pulmonary arterial hypertension and it acts as a vasodilator by relaxing smooth muscles of pulmonary artery and the treatment lasts for long time. 1,2 Extreme variability in oral dosing of HZH, bioavailability of 31% and variable half-life of 3 to 7 h has made the dosage regimen complicated for oral usage.3 Metabolism variations depending on the phenotype and food interactions had much narrowed its oral usage. Low bioavailability, variable and short half-life may not be suitable to meet the therapeutic needs of the patient where the treatment is for longer duration. There is a need for alternative to oral route where hepatic first pass metabolism can be excluded and which can improve the therapeutic activity and quality of life of patient. As the drug has of low molecular weight 196.6 Daltons 4 transdermal delivery is a better alternative to oral route, where a continuous infusion of drug can be provided and patient compliance can be improved. Transdermal systems with a rate control membrane can provide a relatively constant rate of infusion of drug when the drug was maintained in required concentrations in reservoir system where the release rate will depend upon permeation through rate controlling membrane. 5 Hence, in the present work gel drug reservoir of HZH was formulated and the release rate was controlled by using rate controlling membrane and by varying penetration enhancers.Gel reservoir was formulated by using poloxamer a temperature sensitive hydrogel which is very stable, biocompatible and biodegradable polymer. 6,7 Poloxamer solution forms a clear solution at 4-5°C and converts to gel at room temperature.8 Rate controlling membranes were formulated by using E RLPO and E RSPO, the effect of penetration enhancer on release kinetics was evaluated. Pharmacotechnical properties, in vitro, ex vivo studies, stability studies and in vivo pharmacokinetic studies were evaluated. MATERIALS AND METHODS MaterialsHydralazine Hydrochloride was a gift sample received from Hetero drugs Pvt. Ltd, Hyderabad. Poloxamer 407 was provided as gift sample by Hi-Media Laboratories, Mumbai. Eudragit RLPO (E RLPO) and Eudragit RSPO (E RSPO) were gift samples provided by Zhaveri Pharma Chemicals., Mumbai. Release liner (poly iso butylene tape) was purchased from 3M. Hydroxy Propyl Methyl Cellulose (HPMC) and Poly Vinyl Acetate (PVA) were purchased from Hi-Media Laboratories, Mumbai. Azone (AZ), isopropyl myristate (IPM) and menthol (MT) were purchased from S.D Fine chemicals, Mumbai, India. All the solvents and reagents used were of analytical grade. Measurement of sol-gel transition temperatureSol-gel transition temperature was done to determine the poloxamer 407 concentration which retains its gel formation properties at room temperature. Poloxamer 407 solution with different concentrations ABST...

Formulation, Stability Test and in vitro Penetration Test of Emulgel from Tobacco Leaves Extract

“…In the choice of medium, the active substance must be in steady state. 12 The liquid that taken from the receptor compartment is replaced as much as the initial volume liquid is taken. This process is done to keep the receptor fluid volume constant and keep the receptor fluid in steady state.…”