ABSTRACT
The aim of the current study was to design a porous osmotic pump-based drug delivery system for controlled release of oxybutynin. The porous osmotic pump contains pore-forming water-soluble additives in the coating membrane, which after coming in contact with water, dissolve, resulting in an in situ formation of a microporous structure. The dosage regimen of oxybutynin is one 5-mg tablet 2 to 3 times a day. The plasma half-life ranges from approximately 2 to 3 hours. Hence, oxybutynin was chosen as a model drug with an aim to develop a controlled release system for a period of 24 hours. Linear and reproducible release similar to that of Ditropan XL was achieved for optimized formulation (f2 >50) independent of hydrodynamic conditions. The effect of different formulation variables, namely, ratio of drug to osmogent, membrane weight gain, and level of pore former on the in vitro release was studied. Cellulose acetate (CA) was used as the semipermeable membrane. It was found that drug release rate increased with the amount of osmogent because of the increased water uptake, and hence increased driving force for drug release. Oxybutynin release was inversely proportional to the membrane weight gain; however, directly related to the level of pore former, sorbitol, in the membrane. This system was found to deliver oxybutynin at a zero-order rate for 20 hours. The effect of pH on drug release was also studied. The optimized formulations were subjected to stability studies as per International Conference on Harmonisation (ICH) guidelines and formulations were stable after a 3 month study.
Subject(s)
Delayed-Action Preparations , Mandelic Acids/administration & dosage , Chemistry, Pharmaceutical , Drug Stability , Excipients , Hydrogen-Ion Concentration , Mandelic Acids/chemistry , Microscopy, Electron, Scanning , Osmotic Pressure , Porosity , Solubility , TabletsABSTRACT
A few substituted piperazinylphenyloxazolidinone compounds 6-13 having substitution on the distant nitrogen atom of piperazine ring scaffold have been synthesized and evaluated for their antibacterial activity in Gram-positive bacteria. A few compounds showed superior in vitro antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Streptococcus pyogenes than linezolid and eperezolid.
Subject(s)
Anti-Bacterial Agents , Gram-Positive Bacteria/drug effects , Oxazolidinones , Piperazines/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Enterococcus faecalis/drug effects , Enterococcus faecalis/growth & development , Gram-Positive Bacteria/growth & development , Microbial Sensitivity Tests , Oxazolidinones/chemical synthesis , Oxazolidinones/chemistry , Oxazolidinones/pharmacology , Piperazine , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Staphylococcus epidermidis/drug effects , Staphylococcus epidermidis/growth & development , Streptococcus pyogenes/drug effects , Streptococcus pyogenes/growth & developmentABSTRACT
A rapid, simple and sensitive high-performance liquid chromatography-ultra violet (HPLC-UV) method with column switching between sample pre-treatment column and analytical column was developed for the quantitation of rabeprazole in human plasma; on a Bio-Sample Analysis system (Co-sense for BA) from Shimadzu Corporation, Kyoto, Japan. Zaleplon was used as an internal standard. The method was validated as per USFDA guidelines for the concentration range of 20.0-1200.0 ng/mL and the correlation coefficient were found to be better than 0.999. Recovery of rabeprazole as well as the internal standard from human plasma was more than 90.0%. Rabeprazole was stable in human plasma for 4 months at -70 +/- 5 degrees C and for 20.0 h at ambient temperature. In the auto sampler, the drug was stable for 24.0 h at 4 degrees C. The method was specific as there were no interfering peaks in the human plasma eluting at the retention times of the rabeprazole and the internal standard. The frozen plasma samples containing rabeprazole were stable to three freeze thaw cycles. The bioanalytical method was rugged in terms of inter- and intra-day accuracy and precision. The method was simple, specific, sensitive, precise, accurate and suitable for bioequivalence and pharmacokinetic studies. It was successfully applied to the pilot bioequivalence study of 20mg rabeprazole tablet of German Remedies Ltd. (A division of Cadila Healthcare Ltd.), India versus Pariet tablet of Eisai Ltd. & Janssen-Cilag Ltd., Japan in male human subjects.
Subject(s)
Benzimidazoles/blood , Chromatography, High Pressure Liquid/methods , Omeprazole/analogs & derivatives , Omeprazole/blood , Spectrophotometry, Ultraviolet/methods , 2-Pyridinylmethylsulfinylbenzimidazoles , Calibration , Humans , Rabeprazole , Reference Standards , Reproducibility of Results , Sensitivity and Specificity , Therapeutic EquivalencyABSTRACT
Synthesis of a number of 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine substituted oxazolidinones have been reported. They have been screened against a panel of Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. A SAR has been developed. Compound 15 showed comparable activity (MIC) to linezolid and superior to eperezolid.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Enterococcus faecalis/drug effects , Oxazoles/chemical synthesis , Pyridines/chemical synthesis , Staphylococcus aureus/drug effects , Acetamides/pharmacology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial , Linezolid , Methicillin/pharmacology , Microbial Sensitivity Tests , Oxazoles/pharmacology , Oxazolidinones/chemistry , Oxazolidinones/pharmacology , Pyridines/pharmacology , Structure-Activity Relationship , Vancomycin/pharmacologyABSTRACT
A number of substituted piperazinyl oxazolidinone derivatives have been synthesized and their antibacterial activities were evaluated by MIC determination. A systematic SAR was carried out to get highly potent oxazolidinone derivatives.
