Cardiovascular Drug Delivery: Development and Characterization of Captopril Chronomodulated Drug Delivery System using Natural Polymers for the Management of Hypertension

In the present work, different formulations were prepared by and optimized the core tablet prepared by direct compression, incorporating superdisintegrants like Sodium starch Glycolate, Croscarmellose Sodium and Crospovidone, Microcrystalline cellulose used as diluent or filler and magnesium Stearate used as glidant, Lubricant. Then optimization of the formulation was selected based on the drug release. Preformulation studies were performed such as organoleptic properties, angle of repose, bulk density, tapped density, compressibility index, hausner ratio, melting point and solution properties complies as per the specification. Characterization of the drug was done by performing the UV spectroscopy and IR spectroscopy. IR spectrum of the pure drug was compared with that of physical mixture of drug with all the excipients used in the study. The results showed that there was no drug- excipient interaction. The UV spectral analysis of the drug solution indicated that λmax value as 212 & 205 nm. Press coated tablets were prepared by selecting an optimized core tablets C9 and proceed for the coated tablets. The pulsatile coated tablets were prepared by using Natural polymers such as Guar Gum & Xanthan Gum. The pulsatile tablets were prepared by varying concentration of polymers and the compression force from 1 ton to 3 tons. All the prepared press coated were evaluated for hardness, friability, uniformity of weight, drug content uniformity, drug-polymer interaction, in vitro drug release and stability studies. The thickness of the formulations and the hardness was, indicated good mechanical strength of the tablets. Friability, weight variation and drug content uniformity were found to be within official limits for all the formulations. The dissolution studies of Pulsatile coated tablets were carried out by using 0.1 N HCl (1.2 pH) and 6.8 pH Phosphate Buffer. As per the result of dissolution study formulation from the natural polymer-based formulation F12 & F14 were selected as best formulation. Based on all these results, F12 & F14 formulation was selected as the optimized formulations. The optimized formulation F12 & F14 was subjected for stability studies as per ICH guidelines. Formulations subjected for short term stability studies were checked for drug content, hardness, friability and dissolution for 90 days with an interval of 30 days. The formulations were found to be stable as no significant change was observed in the various evaluated parameters of the formulations. CONCLUSION: The aim of the study was to design pulsatile release capsule of Captopril. The rapid release of the drug after a lag time consistent with requirement for chronotherapeutics was achieved with developed formulation. The chronotherapeutic formulations of captopril were developed as press coated tablets using Natural polymers (Guar Gum & Xanthan Gum), different concentrations at different compression force. In this study in addition to effect of natural polymers such as guar gum and xanthan gum on lag time were studied. The polymers such as guar gum and xanthan gum were effectively controlled the lag time. From this study it was concluded that by changing the variables such as the xanthan gum and guar gum to captopril, it may be possible to produce a system with a release profile, which is tailored to meet the particular requirements of the chronotherapeutics drug delivery system. The in vitro studies suggest that xanthan gum tablets of Captopril are promising for the therapy of hypertension. Thus this approach can provide a useful means for pulsatile/programmable release (with single pulse) of Captopril and may helpful for patients with morning surges. A further detailed study in human subjects will through more light on their efficacy and compliance