Amorphous Polymer–Phospholipid Solid Dispersions for the Co-Delivery of Curcumin and Piperine Prepared via Hot-Melt Extrusion

Curcumin and piperine are plant compounds known for their health-promoting properties, but their use in the prevention or treatment of various diseases is limited by their poor solubility. To overcome this drawback, the curcumin–piperine amorphous polymer–phospholipid dispersions were prepared by hot melt extrusion technology. X-ray powder diffraction indicated the formation of amorphous systems. Differential scanning calorimetry confirmed amorphization and provided information on the good miscibility of the active compound–polymer–phospholipid dispersions. Owing to Fourier-transform infrared spectroscopy, the intermolecular interactions in systems were investigated. In the biopharmaceutical properties assessment, the improvement in solubility as well as the maintenance of the supersaturation state were confirmed. Moreover, PAMPA models simulating the gastrointestinal tract and blood-brain barrier showed enhanced permeability of active compounds presented in dispersions compared to the crystalline form of individual compounds. The presented paper suggests that polymer–phospholipid dispersions advantageously impact the bioaccessibility of poorly soluble active compounds.

1. Introduction

The poor solubility of active pharmaceutical agents is a major obstacle to the search for novel oral formulations and causes many promising new drugs to be rejected at an early stage of development due to poor performance in in vivo studies [1]. Currently, many researchers are focusing their efforts on creating delivery systems or formulations to improve solubility. Among the numerous solutions to the problem of poor bioaccessibility are self-emulsifying drug delivery systems, the formation of inclusion complexes with cyclodextrin, obtaining nanoparticles, and the formation of co-crystals [2,3,4].

The problem of developing formulations of active substances with increased solubility is also evident in the manufacturing of nutraceuticals, defined as a food or food component with health benefits [5]. Curcumin and piperine are the main active compounds of the popular spices turmeric (Curcuma longa L.) and black pepper (Piper nigrum L.). These compounds exhibit beneficial health-promoting properties that can be used in the prevention and treatment of many diseases in civilization. Therefore, they can be considered as nutraceuticals. Poor solubility is a limiting factor in the activity of many plant-derived compounds, such as curcumin and piperine. Curcumin has been reported to show several health-promoting properties, such as antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, neuroprotective, and cardioprotective activity [6,7,8]. Piperine, an alkaloid compound, has been reported to exhibit anti-oxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic, anti-obesity, and neuroprotective activity [9,10,11].

One promising formulation approach is the use of an amorphous form of the active ingredient. The amorphous form is characterized by a lack of long-range ordering and, therefore, a lack of crystal structure. This makes the dissolution of the substance in the amorphous form not require the energy inputs needed to release the substance from the crystal structure, so better solubility of the amorphous substance is observed [12]. The use of the amorphous form is associated with the need to ensure product stability. The amorphous form has a natural tendency to transform into a more stable crystalline form, which will result in the loss of the favorable effect on solubility [1]. Thus, it is crucial to reduce the risk of crystallization. The addition of excipients is aimed at providing amorphous form stability. One possible solution is to use a polymer as a matrix in which the active substance is dispersed [13].

Another well-established approach to improving bioavailability is the use of phospholipids. Phospholipids are biocompatible structures composed of a hydrophilic head and a hydrophobic chain, which makes them exhibit an amphiphilic nature. Thanks to their properties of self-organization, emulsification, and wetting, they are used not only in obtaining drug carriers but also as emulsifiers or surfactants [14,15]. Phospholipids can be used in parenteral, oral, or topical formulations [16].

Considering the potential benefits of combining the stabilization of an amorphous form using polymers and phospholipids, this work aimed to develop amorphous dispersions of a polymer–phospholipid and curcumin and piperine to improve the bioaccessibility of these plant-derived compounds. The hot-melt extrusion technology was employed as a method to obtain amorphous dispersions. At first, we established the plasticizing effect of the phospholipid on polyvinylpyrrolidone (PVP) K25 and designed the composition of the polymer–phospholipid blend. In the second stage of the research, we focused on producing and characterizing curcumin–piperine systems dispersed in the polymer–phospholipid matrix.

2.1. Materials

Piperine (purity > 95%, FG) was acquired from Sigma-Aldrich (Sigma-Aldrich, St. Louis, MO, USA), whereas curcumin (purity > 95%) was bought from Xi’an Tian Guangyuan Biotech Co., Ltd. (Xi’an, China). Excipients were provided by the following manufacturers: PVP K25 by JRS Pharma (Rosenberg, Germany), xylitol by Santini (Poznań, Poland), and phosphatidylcholine (from soybean, Type II-S, 14–29% choline basis, purity 21%) by Sigma-Aldrich (St. Louis, MO, USA). The other reagents used were sodium hydroxide (Avantor Performance Materials Poland S.A., Gliwice, Poland), acetic acid (98–100%; POCH, Gliwice, Poland), sodium dimethyl sulfoxide (DMSO; PanReac Appli-Chem ITW Reagents, Darmstadt, Germany), acetic acid (J. T. Baker, Center Valley, PA, USA), and HPLC-grade methanol (J. T. Baker, Center Valley, PA, USA). Using a Direct-Q 3 UV purification system (Millipore, Molsheim, France; model Exil SA 67120), high-grade, laboratory-grade clean water was produced. The suppliers of the Prisma HT, GIT/BBB lipid solution, and acceptor sink buffer were Forest Row, East Sussex, UK-based Pion Inc.

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Wdowiak, K.; Miklaszewski, A.; Cielecka-Piontek, J. Amorphous Polymer–Phospholipid Solid Dispersions for the Co-Delivery of Curcumin and Piperine Prepared via Hot-Melt Extrusion. Pharmaceutics 2024, 16, 999. https://doi.org/10.3390/pharmaceutics16080999

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