Design, Development and Evaluation of Floating Pulsatile Tablets of Captopril for the Morning Surge of Hypertension

INTRODUCTION:ORAL SOLID DOSAGE FORMS: Oral route is the most widely used route of administration among all the routes that have been developed for systemic controlled delivery of drugs. This is due to following reasons: 1. Oral route is most convenient and uncomplicated 2. Ease of administration and safe 3. Improved patient compliance 4. Cost-effective Oral solid forms such as tablets and capsules has been formulated and developed nowadays since they are most effective routes of administration of a new drug. Pharmaceutical products designed for oral delivery and currently available on the prescription and over the counter markets are mostly immediate release type, which is designed for immediate release of drug for rapid absorption.TABLET: Tablet is defined as a compressed solid dosage form containing medicaments with or without excipients. Pharmaceutical tablets are solid, flat or biconvex dishes, unit dosage form, prepared by compressing a drugs or a mixture of drugs, with or without diluents. They vary in shape and different greatly in size and weight, depending on amount of medicinal substance and the intended mode of administration. It is the most popular dosage form and 70% of the total medicines are dispensed in the form of tablet.AIM OF THE WORK: 1. To formulate and evaluate Floating Pulsatile tablet of Captopril providing chronomodulated therapy for better treatment of Hypertension 2. To prepare the rapid release core tablets of Captopril using various superdisintegrants such as sodium starch glycolate, croscarmellose sodium, crospovidone by direct compression 3. Compression coating of optimized core tablets using hydrophilic polymers such as HPMC E5, HPMC K4M, HPMC K15M and Xanthan gum by direct compression.OBJECTIVE:1. To provide drug release at the time when it is needed most. 2. To reduce dose related side effects. 3. To enhance the bioavailability of the drug.SUMMARY AND CONCLUSION:The present work involves the design, development and in-vitro evaluation of Captopril floating pulsatile release tablet, in which the core tablets are rapid release formulation which is coated with hydrophilic polymers such as HPMC E15, HPMC K15M, HPMC K4M, Xanthan gum individually and in combination. FPRT was designed for the treatment of morning surge of Hypertension. The drug excipient interaction was investigated with FTIR spectroscopy. The study indicated that there was no interaction between the drug and the excipients used in the formulations. The rapid release core tablets of captopril were formulated with various concentrations of SSG (2%, 3% and 4%), CCS (1%, 1.5% and 2%) and Crospovidone (2 %, 3.5% and 5%) by direct compression. The formulated RRCT blends were evaluated for pre-compression parameters which showed good flow property. The formulated tablets were found to be within the limits with respect to Weight uniformity, Hardness, Thickness, Diameter and Friability. The Drug content of the formulated Tablets was found to be within the Pharmacopoeial limit. The Disintegration time of Captopril rapid release Core Tablet (Formulation F3) containing 2% croscarmellose sodium disintegrated quickly (D.T = 21 seconds). The in-vitro dissolution studies of the formulated Captopril Core tablets were performed using USP type-II dissolution apparatus. From the formulated batches, the formulation F3 released the drug very quickly (within 4 minutes) when compared to other formulations. Based on the Disintegration and in-vitro release studies of captopril rapid release core tablets, formulation F3 was optimized and selected for Press coating. The outer coat contains hydrophilic polymers (swellable and erodible) such as HPMC E15, HPMC K15M, HPMC K4M, Xanthan gum. For the formulated coating material blends, micromeritic properties were evaluated which showed good flow. So, the Compression coating of optimized Captopril core tablets was done by direct compression technique. Totally 8 batches of Captopril Floating pulsatile release tablets (FPRT) were prepared using HPMC E15, HPMC K15M, HPMC K4M, Xanthan gum.The formulated Captopril FPRTs were found to be within limits with respect to Weight uniformity, Hardness, Thickness, Diameter and Friability. The drug content of the Captopril FPRTs were estimated and found to be within Pharmacopoeial limits. A direct correlation between swelling and lag time was observed and found that the formulations having maximum swelling indices showed higher lag time. The in-vitro dissolution studies of the formulated Captopril FPRTs were performed using USP type-II dissolution apparatus. From the formulated batches, the % drug release for the formulation FP8 was 101.23% at the end of 7.5hrs with the lag time of 6hours. Based on the in-vitro release studies of Captopril FPRT, formulation FP8 (formulation contains 200mg of HPMC E15 and 50mg of HPMC K4M) was optimized. The optimized FPRT (FP8) follows Zero order kinetics up to the lag time, in which the regression value was 0.963. The ‘n’ value of Korsmeyer-peppas equation was found to be 1.066. From this it was concluded that the drug release follows non-fickian super case II transport. A stability study for the optimized Captopril FPRT was performed by storing the tablets at ambient room temperature and at 40ºC ± 2ºC maintained at RH 75% ± 5% for 45 days. There was no significant differences produced in physical appearance, drug content and % drug release, this shows that the formulation remains stable during the storage