Formulation Approaches to Crystalline Status Modification for Carotenoids: Impacts on Dissolution, Stability, Bioavailability, and Bioactivities

Abstract

Carotenoids, including carotenes and xanthophylls, have been identified as bioactive ingredients in foods and are considered to possess health-promoting effects. From a biopharmaceutical perspective, several physicochemical characteristics, such as scanty water solubility, restricted dissolution, and susceptibility to oxidation may influence their oral bioavailability and eventually, their effectiveness. In this review, we have summarized various formulation approaches that deal with the modification of crystalline status for carotenoids, which may improve their physicochemical properties, oral absorption, and biological effects. The mechanisms involving crystalline alteration and the typical methods for examining crystalline states in the pharmaceutical field have been included, and representative formulation approaches are introduced to unriddle the mechanisms and effects more clearly.

Keywords: carotenoids; crystallization status modification; formulation approaches.

Figure 1

The structure of carotenes and xanthophylls.

Figure 2

The structures of E (trans)- and Z (cis)- forms of β-carotene.

Figure 3

The difference among amorphism, polymorphism, and pseudo-polymorphism.

Figure 4

PXRD profiles of β-carotene and its nanoformulations.

Figure 5

DSC thermograms of β-carotene, a β-carotene-PLGA-PVP physical mixture, and β-carotene-loaded PLGA-PVP nanoparticles.

Figure 6

Formulation conditions affecting crystallization.

Figure 7

The concept of confinement and the relationship between confinement and crystals.

Figure 8

The scheme of solid dispersions.

Figure 9

Scheme diagrams of (A) cyclodextrin, (B) amylose, and (C) β-lactoglobulin inclusion complexes [81,82,83].

Figure 10

The mechanism of trapping amorphous APIs in nanoparticles via nanoprecipitation [96].

Figure 11

Illustration of a lipid-based formulation.

Figure 12

The mechanism of crystallization suppression in a lipid-based formulation.

Figure 13

The mechanism of the “Spring and Parachute”.

Figure 14

Schematic of the hydrophilic and lipophilic compounds within a liposome. The right indicates that the hydrophilic compounds in the core may undergo crystallization and precipitation.