DESIGN, CHARACTERIZATION AND PHARMACOCKINETIC EVALUATION OF CHRONOMODULATED METOPROLOL TARTARATE PULSATILE DRUG DELIVERY SYSTEM
The chronological behavior of Hypertension confirms increased blood pressure at early morning hours, need a preferable dosage form which will provide desired concentration of the drug at pre-determined time points especially in early morning hours. Pulsatile dosage forms are designed to mimic the circadian rhythm by releasing the drug at the desired time, by means of an internal preprogrammed designed dosage form that is initiated when the dosage form comes in contact with gastrointestinal fluids especially in colon. The prepared dosage forms were optimized and evaluated both in vitro and in vivo evaluation. Metoprolol tartarate, a selective beta blocker pulsincaps were formulated using, body of the capsules with modified solubility by coating with formaldehyde and polymer plug of Eudragit L 100 was fitted in mouth of body of the capsule. The results of the final two optimized formulation P1 and P2 was found to ideal for pulsatile release. The maximum in vitro drug release of 101.24± 1.24 and 101.08± 1.54 % (first pulse Metoprolol tartarate granules immediately release the drug after dinner from the uncoated cap of the capsule), 94.84±1.4% and 97.74±1.8 (Second pulse at early morning hours after lag time in Colonic pH). The selected formulations of Metoprolol tartarate pulsincaps (P1 and P2) were subjected for pharmacokinetic studies using male albino rats. From the Pharmacokinetic studies, in-vivo studies shown that increased AUC, relative bioavailability and delayed time of Metoprolol tartarate pulsincap proves the Sustainability and targetability of drug in colon