ABSTRACT
Rheumatoid arthritis is an auto immune disease which requires chronotherapy as it occurs during early morning. Tramadol hydrochloride (TH) is an analgesic drug, used to treat rheumatoid arthritis. The aim of the present investigation was to develop chronomodulated drug delivery system of tramadol hydrochloride such that it releases the drug early in the morning, during which the symptoms of rheumatoid arthritis worsen. To develop chronomodulated drug delivery system of TH, initially core tablets of TH were prepared using three different supradisintegrants followed by coating with pH dependent polymer of Eudragit S100. The prepared core tablets are evaluated for physical parameters and an optimal system was identified. Further, coating composition of Eudragit S100 was optimized and coating tablets of TH was prepared. The prepared coated tablets were evaluated for weight variation, hardness, drug content and in vitro release studies in 0.1N HCl, pH 6.8 phosphate buffer and pH 7.4 phosphate buffer. Formulation with 7.5% of coating solution (ES2) had shown a significant drug release after a lag time of 3 h (in pH 6.8 medium), 6 h (in pH 6.8 medium) and 8 h (in pH 7.4 medium), respectively. DSC studies revealed that no interaction between core and coated materials with drug was observed. Thus, chronomodulated drug delivery system of TH was formulated and assuming that if a tablet is administered around 9 pm to 10 pm, the drug release starts after a lag time of 6 h i. e., around 3am to 4 am.
Subject(s)
Drug Chronotherapy , Drug Delivery Systems/methods , Tramadol/administration & dosage , Drug Liberation , Hydrogen-Ion Concentration , In Vitro Techniques , Polymethacrylic Acids/chemistry , Tablets/chemistry , Tramadol/chemistryABSTRACT
PURPOSE: The present study was carried out to investigate the pharmacokinetic and pharmacodynamic drug interaction of irbesartan with glipizide after single and multi dose treatment in normal and hypertensive rat models to evaluate the safety and effectiveness of the combination. METHODS: The study was conducted on normal and 10% fructose solution induced hypertensive rats. Irbesartan and glipizide were administered orally for 7 days and on 8th day blood samples were collected for 12 h at regular time intervals from irbesartan alone and in combination with glipizide treated groups. The blood samples were analyzed for various pharmacokinetic and pharmacodynamic parameters. RESULTS: Irbesartan caused marked reduction in blood pressure in hypertensive rats. The combination of irbesartan and glipizide in hypertensive rats produce significant change in blood pressure (pharmacodynamic) and also significance in pharmacokinetic parameters of irbesartan with glipizide in single dose and multiple doses. CONCLUSION: The results of present study demonstrated that the synergistic activity of irbesartan with glipizide was observed.