Lag time

A Pulsatile drug delivery system delivers drug in rapid and burst manner within a short time after a lag time. There are many situations where drug is needed to be released immediately (after bursting the delaying film coat) at specific site. The aim of present work is to develop Pulsatile drug delivery of Tiotropium Bromide using press coating method. All the formulations have shown satisfactory results for various physicochemical parameters like hardness, friability, thickness, weight variation. Ethyl cellulose has predominant effect on the lag time, while also shows significant effect on drug release.  Press coated tablet shows a delayed release pattern. Among all the core tablet formulations T7 was selected based on drug release within a given period of time.  In-vitro release rate studies showed that the P3T7 was optimized based on less amount of drug release during lag time. Formulations P3T7 found to be stable at 45o C and 75% RH for a period of 6 months. FT-IR studies revealed that there was no interaction between Tiotropium bromide and the polymers. Keywords: Pulsatile drug delivery, circadian rhythms, Tiotropium Bromide, Lag time, Press coated tablets.

The main objective of the present investigation was to formulate and evaluate chronomodulated pulsatile drug delivery system of Trimetazidine Hydrochloride which was aimed to release the drug after lag time (6 hrs) in order to mimic circardian rhythm of Angina Pectoris.Preformulation studies and compatibility studies were carried out for drug and excipients. Core tablet was prepared by direct compression using sodium starch glycolate as superdisintegrant and press coated with different polymer & varying its ratio. Further prepared tablets were optimized using 32 full factorial design. Nine batches were prepared varying the amount of polymer and ratio of polumer (HPMC K4M: EC) and they were evaluated for precompressional and postcompressional tests. Optimized batch was derived statistically using desirability function (Minitab 17).The Model was validated by formulating the check point batch. Accerelated stabilitiy study was carried out of optimized batch. Preformulation and compatibility studies was carried out using FTIR , DSC which shows satisfactory results, no interaction was found between drug and excipients. Press coating of core tablet with the combination of HPMC K4M and EC was found to be providing the desired release. Results of precompressional and postcompressional was found to be within the limits. Varying  the amount of coating and ratio of polymer have significant effect on lag time(Y1) as well as on time required for 90% drug release (Y2).Optimized batch shows lag time of 6 hrs followed by complete release within 1 hrs which is desiered in case of pulsatile delivery. No significant bias was found between predicted and observed value of check point batch.The data of stability study revealed that the optimized formulation is stable. Pulsatile drug delivery system of Trimetazidine Hydrochloride for chronomodulated therapy can be prepared by press coating technique using 200 mg of coating and HPMC K4M:EC(10:90) ratio of polymer which will provide lag time of 6hrs and complete release within 1 hrs.

Traditionally, drugs are released in an immediate or extended fashion. A pulsatile drug release, where the drug is released rapidly after a well defined lag-time, could be advantageous for many drugs or therapies. Pulsatile release systems can be classified in multiple-pulse and single-pulse systems. A popular class of single-pulse systems is that of rupturable dosage forms. Other systems consist of a drug-containing core, covered by a swelling layer and an outer insoluble, but semi-permeable polymer coating or membrane. The lag time prior to the rupture is mainly controlled by: (i) the permeation and mechanical properties of the polymer coating and (ii) the swelling behavior of the swelling layer. As is frequently found in the living body, many vital functions are regulated by pulsed or transient release of bioactive substances at a specific site and time. Thus it is important to develop new drug delivery systems to achieve pulsed delivery of a certain amount of drugs in order to mimic the function of the living systems, while minimizing undesired side effects. These dosage forms offer many advantages, such as nearly constant drug level at the site of action, prevention of peak-valley fluctuations, reduction in dose of drug, reduced dosage frequency, avoidance of side effects, and improved patient compliance. Key words: Lag time, pulsatile drug release, Rupturable coating