Chronotherapeutic drug delivery for early morning surge in blood pressure: a programmable delivery system.

The purpose of the study was to develop pulsatile capsule dosage form of valsartan for controlled delivery. In the majority of individuals blood pressure rises in the early morning hours, which lead to serious cardiovascular complications. Formulations with constant/programmable delivery rates make it possible to deliver drug at definite time or controlled rate in chronopharmacokinetic studies. The prepared system contained swellable polymer (l-hydroxypropyl cellulose (L-HPC), xanthan gum, polyethylene oxide or sodium alginate) together with drug tablet and erodible tablet (L-HPC or guar gum) in a pre-coated capsule. Various formulation factors were investigated through series of tests, in vitro dissolution and ex vivo continuous dissolution-absorption studies. We found that the type, amount of polymers and erodible tablet influenced the drug release. The formulation containing 200 mg sodium alginate and erodible tablet (150 mg) containing 50% guar gum and 46% lactose showed 5-6 h lag time and 10+/-2.1% drug release in initial 6 h following rapid release (99+/-1.7% release in 12 h) of drug was observed. The continuous dissolution-absorption study conducted using everted rat intestinal segment indicated delay in absorption of drug. Thus this approach can provide a useful means for timed release of valsartan and may be helpful for patients with morning surge.

Multiparticulate drug delivery system of aceclofenac: development and in vitro studies.

The aim of this study was to develop an enteric-coated multiunit dosage form containing aceclofenac, a nonsteroidal anti-inflammatory drug. The pellets were prepared by using extrusion/spheronization method, and the core pellets were coated with a pH-sensitive poly(meth) acrylate copolymer (Eudragit L100-55) to achieve site-specific drug release. The formulated pellets were characterized for percentage yield, size distribution, surface morphology studies, drug content, and flow properties. In vitro dissolution test was used for comparison of drug release profiles of various coated pellets. The practical yield was found to be 90-95%. The particle size of enteric-coated pellets was found to be in the range of 0.59-0.71 mm. The pellets were spherical in shape and surfaces of pellets were found to be rough and showing micropores. Enteric-coated pellets showed good flow properties and in vitro dissolution profile. Dissolution tests were carried out in a USP type II dissolution apparatus in media-simulating pH conditions of the gastrointestinal tract. The release of the aceclofenac from formulated pellets was established to be minimum in the pH 1.2 (<5%) for a period of 2 h, and at pH 6.8, it shows the maximum release (85 +/- 5% release within 1 h) which indicates gastric resistance of the formulated pellets. The 20% wt/wt enteric-coated pellets were compared to that of marketed product (tablets), it was observed that pellets showed better release profile. The study concluded that the formulated multiparticulate dosage forms can be used as an ideal drug delivery system for the aceclofenac.