Dipen R. Bhimani

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.

A major problem in ocular therapeutics is the attainment of optimal drug concentration at the site of action, which is compromised mainly due to precorneal loss resulting in only a small fraction of the drug being ocularly absorbed. Brimonidine tartrate is an antiglaucomic agent which shows rapid precorneal exclusion and reduced ocular bioavailability when given in form of conventional ophthalmic formulations. The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions may be overcome by the use of in-situ gel forming ophthalmic systems that are instilled as drops into the eye and undergo a sol–gel transition in the cul-de-sac. In the present study, environmentally responsive ophthalmic drug delivery system composed of two gelling polymers with different phase transition mechanisms was developed. Combination of polyacrylic acid (carbopol 934P) and xanthan gum was investigated as ophthalmic vehicle. Different ratios of these polymers were used to prepare environmentally responsive ophthalmic drug delivery system by simple mixing procedure. Developed formulation was assessed for various evaluation parameters such as appearance/clarity, pH, gelation, drug content, rheological measurement, in-vitro release, and sterility testing and stability study. Prepared formulation showed agreeable appearance/clarity, acceptable pH and good gelation property. In-vitro studies demonstrated adequate drug content, desired rheological behaviour and reasonable in-vitro drug release property. Formulation was stable over one month period. In conclusion, the optimum concentration of polymers results in minimized drug loss and sustained drug release. On the basis of these findings, prepared in-situ gel may be considered as a viable alternative to conventional brimonidine tartrate eye drops.