Abstract

Lipid-based formulations can circumvent the low aqueous solubility of problematic drug compounds and increase their oral absorption. As these formulations are often physically unstable and costly to manufacture, solidification has been suggested as a way to minimize these issues. This study evaluated the physicochemical stability and in vitro performance of lipid-loaded mesoporous magnesium carbonate (MMC) particles with an average pore size of 20 nm. A medium chain lipid was loaded onto the MMC carrier via physical adsorption. A modified in vitro lipolysis setup was then used to study lipid release and digestion with 1H nuclear magnetic resonance spectroscopy. The lipid loading efficiency with different solidification techniques was also evaluated. The MMC, unlike more commonly used porous silicate carriers, dissolved during the lipolysis assay, providing a rapid release of encapsulated lipids into solution. The digestion of the dispersed lipid-loaded MMC therefore resembled that of a coarse dispersion of the lipid. The stability data demonstrated minor degradation of the lipid within the pores of the MMC particles, but storage for three months did not reveal extensive degradation. To conclude, lipids can be adsorbed onto MMC, creating a solid powder from which the lipid is readily released into the solution during in vitro digestion. The chemical stability of the formulation does however merit further attention.

Highlights

  • The cost of developing drug therapies is continually increasing, and capitalized costs are currently around 1.8 billion USD for a large pharmaceutical company to bring a new molecular entity to the market [1]

  • The physicochemical properties of the CAP-magnesium carbonate (MMC) manufactured by simple physical adsorption was extensively characterized to allow for comparison with solid lipid-based formulations (LBFs) produced but using different mesoporous carriers [13,14,15,16]

  • This is consistent with that reported for the mesoporous silicate, Neusilin US2, when loaded with LBFs in similar weight ratios via physical adsorption [12,13,16]

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Summary

Introduction

The cost of developing drug therapies is continually increasing, and capitalized costs are currently around 1.8 billion USD for a large pharmaceutical company to bring a new molecular entity to the market [1]. With up to 90% of drug candidates in the pipeline being classified as poorly soluble, low aqueous solubility poses a major challenge to effective pharmaceutical oral product development [3,4]. Various advanced drug delivery systems have been introduced to overcome solubility challenges, including amorphous solid dispersions and lipid-based formulations (LBFs) [4,5,6,7]. The solidification methods vary in both execution and complexity, but commonly applied methods include physical adsorption, freeze-drying, spray-drying and hot melt extrusion. Common carriers for adsorption of LBFs include silicon dioxide, magnesium aluminometasilicate, calcium silicate, and porous dibasic calcium phosphate [8,9,11]

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