pulsatile

Concomitant therapy of anti inflammatory agent and disease modifying drug in pulsatile pattern proves the best treatment for pain relief and in remission of disease. In the current work, combination therapy of aceclofenac and leflunomide was studies for rheumatoid arthritis. Tab in tab formulation was developed with inner leflunomide and outer aceclofenac fraction. Outer fraction provides instant relief from symptomatic pain and inner part provides disease remission. pH sensitive polymers were investigated for coating and coating parameters were optimized. Considering the pH solubility of Eudragit S 100 and Eudragit L 100 in different ratio, final composition was derived. With final composition, desired lag phase observed in the drug release study. Further, X-ray studies and Pharmacokinetic study with final formulation also proves the efficacy of the final formulation w.r.t. desired lag phase and drug plasma concentration in-vivo. Final formulation found stable in 3 months stability study w.r.t. physical and chemical parameters. Optimized novel pulse release combination therapy developed to provide the relief to arthritis patient. 

Modified release dosage forms have acquired a great importance in the current pharmaceutical research. It denotes a formulation of a medicinal agent that releases the active ingredients over several hours, in order to maintain a relatively constant plasma concentration of the drug. In addition, sustained and controlled release devices are not applicable in some cases like time-programmed administration of hormones and many drugs. The living systems are predictable dynamic resonating systems which require different amounts of drug at expected times within the circadian cycle.  Pulsatile drug delivery system has fulfilled this requirement. This system is such a system where drug is released suddenly after well-defined lag time or time gap according to circadian rhythm of disease states. No drug is released from the device within this lag time. This method is good for the drugs with extensive first pass metabolism and targeted to specific site in the intestinal tract. Pulsatile drug delivery system classified as time controlled pulsatile release, stimuli induced, chemical stimuli induced pulsatile systems, external stimuli pulsatile release etc.

Chronopharmaceutics is a branch of pharmaceutics devoted to the design and evaluation of drug delivery systems that release a bioactive agent at a rhythm that ideally matches the biological requirement of a given disease therapy. A major objective of chronotherapy in the treatment of several diseases is to deliver the drug in higher concentrations during the time of greatest need according to the circadian onset of diseases or symptoms. The main objective of the present study is to develop single-unit pulsatile drug delivery system for obtaining no drug release till it reaches in colon followed by pulsed drug release in colon to achieve chronotherapeutic release of atenolol for treatment of hypertension and to improve the patient compliance. In vitro studies revealed that the tablet coated with guar gum and Eudragit S-100 have limited drug release in stomach and small intestinal environment and released maximum amount of drug in the colonic environment. Programmable pulsatile, colon-specific release has been achieved from tablet of T7 formulation (50:50) which meet demand of chronotherapeutic drug delivery. Key Words: pulsatile, chronotherapeutic, hypertension, atenolol