The present study investigates the physicochemical properties and stability of a novel lipid-based formulation-surfactant-enriched oil marbles containing abiraterone acetate. While the biopharmaceutical performance of this formulation has been reported recently, this study aims to fill the gap between a promising in vivo performance and industrial applicability. A series of techniques were employed to assess the solid-state characteristics of oil marble cores along with their physicochemical properties upon stability testing. The chemical stability of abiraterone acetate in the formulation was also investigated. The core of the formulation was found to be stable both physically and chemically over 12 months of storage. The in vitro performance of stressed samples was evaluated using a dissolution experiment. The formulation has successfully self-emulsified upon incubation in bio-relevant media, resulting in a fast and complete API release. An important issue connected with the excipient used as a covering material of oil marbles has been identified. The seemingly insignificant water sorption caused agglomeration of the oil marbles and consequently compromised the dissolution rate in some of the stressed samples. Replacing HPMC with lactose as a covering material resulted in more favorable properties upon storage. Overall, it has been shown that oil marbles are an industrially applicable concept of the solidified lipid-based formulation.
Abiraterone acetate has limited bioavailability in the fasted state and exhibits a strong positive food effect. We present a novel formulation concept based on the so-called oil marbles (OMs) and show by in vitro and in vivo experiments that the food effect can be suppressed. OMs are spherical particles with a core-shell structure, formed by coating oil-based droplets that contain the dissolved drug by a layer of powder that prevents the cores from sticking and coalescence. OMs prepared in this work contained abiraterone acetate in the amorphous form and showed enhanced dissolution properties during in vitro experiments when compared with originally marketed formulation of abiraterone acetate (Zytiga®). Based on in vitro comparison of OMs containing different oil/surfactant combinations, the most promising formulation was chosen for in vivo studies. To ensure relevance, it was verified that the food effect previously reported for Zytiga® in humans was translated into the rat animal model. The bioavailability of abiraterone acetate formulated in OMs in the fasted state was then found to be enhanced by a factor of 2.7 in terms of AUC and by a factor of 4.0 in terms of Cmax. Crucially, the food effect reported in the literature for other abiraterone acetate formulations was successfully eliminated and OMs showed comparable extent of bioavailability in a fed-fasted study. Oil marbles therefore seem to be a promising formulation concept not only for abiraterone acetate but potentially also for other poorly soluble drugs that reveal a positive food effect.
- MeSH
- abirateron aplikace a dávkování chemie farmakokinetika MeSH
- aplikace orální MeSH
- biologická dostupnost MeSH
- farmaceutická vehikula chemie MeSH
- interakce mezi potravou a léky MeSH
- krysa rodu rattus MeSH
- modely u zvířat MeSH
- oleje chemie MeSH
- omezení příjmu potravy fyziologie MeSH
- plocha pod křivkou MeSH
- postprandiální období fyziologie MeSH
- povrchově aktivní látky chemie MeSH
- příprava léků metody MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Many new therapeutic candidates and active pharmaceutical ingredients (APIs) are poorly soluble in an aqueous environment, resulting in their reduced bioavailability. A promising way of enhancing the release of an API and, thus, its bioavailability seems to be the use of liquid oil marbles (LOMs). An LOM system behaves as a solid form but consists of an oil droplet in which an already dissolved API is encapsulated by a powder. This study aims to optimize the oil/powder combination for the development of such systems. LOMs were successfully prepared for 15 oil/powder combinations, and the following properties were investigated: particle mass fraction, dissolution time, and mechanical stability. Furthermore, the release of API from both LOMs and LOMs encapsulated into gelatine capsules was studied.
- MeSH
- biologická dostupnost MeSH
- časové faktory MeSH
- chemie farmaceutická MeSH
- nosiče léků chemie MeSH
- oleje chemie MeSH
- prášky, zásypy, pudry MeSH
- příprava léků metody MeSH
- rozpustnost MeSH
- stabilita léku MeSH
- tobolky MeSH
- uvolňování léčiv MeSH
- voda chemie MeSH
- želatina chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A liquid marble is a liquid droplet encapsulated in a hydrophobic powder that adheres to the liquid surface. Liquid marbles preparation is very simple – a small amount of liquid is carefully dripped on the layer of hydrophobic powder consisting of nano- or micro particles, which spread spontaneously at the interface liquid/air. This process results in a liquid marble that has some of the properties of a liquid droplet and, at the same time, behaves as a soft solid. Liquid marbles present an alternative to superhydrophobic surfaces because these particles prevent the liquid to wet and contaminate the carrier surface, be it solid or liquid. The present work focuses on the description of basic properties of liquid marbles; also, an overview is given of possible applications of liquid marbles, e.g. for the transport of small volumes of liquids or powders in microfluidics, for the detection of gases or water contamination or as (bio)microreactors.
The ability to simulate the 3D structure of a human body is essential to increase the efficiency of drug development. In vivo conditions are significantly different in comparison to in vitro conditions. A standardly used cell monolayer on tissue culture plastic (2D cell culture) is not sufficient to simulate the transfer phenomena occurring in living organisms, therefore, cell growth in a 3D space is desired. Drug absorption, distribution, metabolism, excretion and toxicity could be tested on 3D cell aggregates called spheroids, decrease the use of animal models and accelerate the drug development. In this work, the formation of spheroids from HT-29 human colorectal adenocarcinoma cells was successfully achieved by means of the so-called liquid marbles, which are liquid droplets encapsulated by a hydrophobic powder. During the cultivation in the medium inside the liquid marbles, cells spontaneously formed spherical agglomerates (spheroids) without the need of any supporting scaffold. The study focused on the influence of different parameters—namely liquid marble volume, seeding cell density and time of cultivation—on the final yield and quality of spheroids. This work has shown that using liquid marbles as microbioreactors is a suitable method for the cultivation of HT-29 cells in the form of spheroids.
