Reconstitutable spray dried ultra-fine dispersion as a robust platform for effective oral delivery of an antihyperlipidemic drug

Abstract

The current article highlights the application of spray drying technique to produce an ultra-fine powder encapsulating the antihyperlipidemic drug, atorvastatin calcium (ATV). First, ATV was dissolved in an emulsion formulation, and different carriers (pectin, alginate, chitosan HCl and hydroxypropylmethyl cellulose) in two concentrations (1.5 and 3%) were added. Then, these carrier-containing formulations were subjected to spray drying, whereby ultra-fine ATV-loaded spray dried emulsions were produced (ATV-SDE). The optimum formulation; ATV-SDE7 containing 3% w/w pectin was selected showing an obviously enhanced dissolution profile compared to the other used polymers which could be attributed to its lower ability to swell in acidic medium, resulting in faster drug diffusion into release medium. Thus, ATV-SDE7 was subjected to further characterization including; DSC, XRPD, SEM and flowability properties. In-vivo studies were conducted using high-fat induced hyperlipidemic rats. The optimum formulation depicted normal lipid profile showing significant reduction in the measured parameters at the end of daily oral treatment, compared to ATV marketed tablets and control hyperlipidemic rats confirmed by normal liver sections upon histopathological examination. The superior lipid-lowering activity of ATV-SDE7 was not only due to the enhanced dissolution of ATV but also due to the presence of pectin which is capable of lowering both cholesterol and triglyceride serum levels. Hence, the present study suggests that the formulation strategy employing ultrafine redispersible spray dried emulsion with pectin as a carrier holds a promising approach for the development of a novel dosage form of enhanced antihyperlipidemic effect for ATV.