Chronotherapeutics also known as pulsatile drug delivery system deals with the study of the temporal changes in absorption, distribution, metabolism and elimination and thus takes into account the influence of time of administration on these different steps and it focuses on the release of a drug after a lag time at a particular site in order to maintain constant blood levels of a particular drug matching circadian rhythms of various diseases. Circadian time dependent differences are also seen in pharmacokinetics of many classes of medications like cardiovascular active drugs, NSAID's, antidepressants, anti hypertensives, local anesthetics, H 1 and H 2 antagonists etc. The role of circadian rhythms in the mechanisms of disease and the pharmacokinetics and pharmacodynamics of medications constitutes a challenge to drugdiscovery and drug-delivery scientists. We must strive to develop intelligent drug-delivery systems that can affect a target cell or organ system at that circadian time when it is possible to optimize desired therapeutic outcomes and minimize or avert adverse effects. The recent advances in pulsatile drug delivery technology are CODAS, ACCU-BREAK, SODAS, IPDAS, DMDS Technology etc.
A n extended release tablet provides prolonged release of drug, maintains the desired concentration of drug in plasma and thereby reduce dosing frequency, improve patient compliance and reduce the dose-related side-effects. Ranolazine is indicated for the chronic treatment of angina in patients who have not achieved an adequate response with other anti-anginal agent. The present investigation was undertaken to design the extended release tablets of ranolazine employing different polymers as matrix forming agents using direct compression technique. Formulated tablets were evaluated for weight variation, hardness, friability, drug content, swelling index and in vitro release studies. The drug release followed first order kinetics and controlled by both erosion and diffusion mechanism. It is concluded that the desired drug release pattern can be obtained from the formulation containing 9.8% w/w eudragit and 39.2% w/w metallose offered relatively much slow release of ranolazine compared with other formulations. The selected formulation showed a similarity factor 76 when comparing in vitro dissolution data of the commercial formulation ranozex 500.
The N-oxide of anti-psychotic drug Blonanserin (BLNO) was synthesized and tested as a novel molecule to understand its ability in reducing blood glucose levels. Administration of BLNO at 1 mg/kg (mpk, mg of drug per kg of rat body weight) to diabetic Wistar rats (induced by treatment of 40 mg/kg streptozotocin, STZ) showed reduced glucose levels at 100 mg/dL in a 28 day study, compared to the control group (with no drug added only STZ induced) which reached hyperglycemic levels of 500-600 mg/dL. At 5 mpk of BLNO, glucose levels were controlled in a 18 day study and no toxic or adverse indications were observed at the higher 5X dose. Oral glucose tolerance test on Wistar rats confirmed the potential of BLNO to reduce glucose levels at 5 mpk dose, comparable to that of marketed drugs metformin HCl (MHCL) and sitagliptin phosphate monohydrate (SPMH) at 100 mpk dose in 90-120 min after drug administration. A novel molecule Blonanserin-N-oxide is identified as a potential anti-diabetic drug lead for controlling blood glucose levels.
Due to the increasing microbial resistance to antibacterial and antifungal drugs, the development of
new antimicrobial agents is an urgent priority. In search of newer antimicrobial agents, a series of
4,5-disubstituted-3-mercapto-1,2,4-triazole derivatives were synthesized from aromatic acids and
substituted isothiocyanates. The in silico study was performed to study the binding interactions of the
synthesized compounds with the active pocket of CYP51. Among the synthesized 3-mercapto-triazole
derivatives, compounds 6r, 6s and 6u exhibited promising antimicrobial activity comparable to standard
drugs. The results suggested that the structural modification to 3-mercapto-1,2,4-triazole derivatives
could lead to promising antimicrobial scaffolds.
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