“…1). Adler et al prepared an amorphous solid dispersion composed of a mixture of b-carotene, polymer, lipid, and silica by the hot-melt extrusion method and studied its physicochemical properties (Adler et al 2016). They reported that the structure of this solid dispersion was influenced by H-bonding and ion-dipole interactions between lipid and silica.…”
b-Carotene is a member of the carotenoid family and is a red-orange pigment abundantly present in many vegetables and fruits. As an antioxidant, it eliminates excessive reactive oxygen species generated in the body. Accordingly, it has potential to be used in the pharmaceutical, food, and cosmetic industries. b-Carotene has a very low water solubility and low bioavailability; thus, there is a need to develop techniques to overcome these issues. In this study, we aimed to enhance the water solubility of b-carotene by using hot-melt technology, a type of solid dispersions technology. When preparing b-carotene solid dispersion using this method, suitable conditions for the emulsifiers and mixing ratios were investigated using water solubility as an index. Setting the weight ratio of bcarotene:polyvinylpyrrolidone:sucrose fatty acid ester to 10%:70%:20% resulted in the poorly-water soluble b-carotene showing improved water solubility (120 lg/mL). The physicochemical properties of the optimized b-carotene solid dispersion were analyzed using field emission scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. The solid dispersion was found to have an amorphous structure. The improved solubility observed for b-carotene in the solid dispersions developed in this work may make these dispersions useful as additives in foods or in nutraceutical formulations. Keywords b-Carotene Á Emulsifier Á Water solubility Á Hot-melt technology Á Solid dispersion Á Amorphous Kenji Ishimoto and Shohei Miki have contributed equally to this work.
“…1). Adler et al prepared an amorphous solid dispersion composed of a mixture of b-carotene, polymer, lipid, and silica by the hot-melt extrusion method and studied its physicochemical properties (Adler et al 2016). They reported that the structure of this solid dispersion was influenced by H-bonding and ion-dipole interactions between lipid and silica.…”
b-Carotene is a member of the carotenoid family and is a red-orange pigment abundantly present in many vegetables and fruits. As an antioxidant, it eliminates excessive reactive oxygen species generated in the body. Accordingly, it has potential to be used in the pharmaceutical, food, and cosmetic industries. b-Carotene has a very low water solubility and low bioavailability; thus, there is a need to develop techniques to overcome these issues. In this study, we aimed to enhance the water solubility of b-carotene by using hot-melt technology, a type of solid dispersions technology. When preparing b-carotene solid dispersion using this method, suitable conditions for the emulsifiers and mixing ratios were investigated using water solubility as an index. Setting the weight ratio of bcarotene:polyvinylpyrrolidone:sucrose fatty acid ester to 10%:70%:20% resulted in the poorly-water soluble b-carotene showing improved water solubility (120 lg/mL). The physicochemical properties of the optimized b-carotene solid dispersion were analyzed using field emission scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. The solid dispersion was found to have an amorphous structure. The improved solubility observed for b-carotene in the solid dispersions developed in this work may make these dispersions useful as additives in foods or in nutraceutical formulations. Keywords b-Carotene Á Emulsifier Á Water solubility Á Hot-melt technology Á Solid dispersion Á Amorphous Kenji Ishimoto and Shohei Miki have contributed equally to this work.
“…relatively lower temperature and mechanical activity) compared to temperature-based and mechanical-based methods make them more flexible in terms of selecting the best compound and excipient, as long as both components are miscible and soluble in the solvent system used. However, more stringent criteria are required for temperature-based methods, including criteria for the T g and the T m of both the compound and the excipient, the viscosity of the excipient, the miscibility of the components, the extrudability of the mixture, and the potential degradation of the compound on exposure to high temperature during the process (74,76,103,109,129,138,150,155,175). These could limit the applicability and use of temperature-based methods in the preparation and study of amorphous formulations.Fig.…”
Section: Current Status Of Research On Amorphous Formulationsmentioning
The alarming numbers of poorly soluble discovery compounds have centered the efforts towards finding strategies to improve the solubility. One of the attractive approaches to enhance solubility is via amorphization despite the stability issue associated with it. Although the number of amorphous-based research reports has increased tremendously after year 2000, little is known on the current research practice in designing amorphous formulation and how it has changed after the concept of solid dispersion was first introduced decades ago. In this review we try to answer the following questions: What model compounds and excipients have been used in amorphous-based research? How were these two components selected and prepared? What methods have been used to assess the performance of amorphous formulation? What methodology have evolved and/or been standardized since amorphous-based formulation was first introduced and to what extent have we embraced on new methods? Is the extent of research mirrored in the number of marketed amorphous drug products? We have summarized the history and evolution of amorphous formulation and discuss the current status of amorphous formulation-related research practice. We also explore the potential uses of old experimental methods and how they can be used in tandem with computational tools in designing amorphous formulation more efficiently than the traditional trial-and-error approach.
“…Figure depicts AFM images of the different extrudate products with drug. Extrudates with MA displayed some micropores (Figure A,B) but the submicron structure was very homogeneous in the case of matrix extrusion (Figure A) and slightly less homogeneous for direct extrusion (Figure B) because of the formation of small domains that were only visible at a high magnification . However, there was no clear indication of a phase separation in both formulations containing MA.…”
Hot
melt extrusion (HME) has become an essential technology to
cope with an increasing number of poorly soluble drug candidates.
However, there is only a limited choice of pharmaceutical polymers
for obtaining suitable amorphous solid dispersions (ASD). Considerations
of miscibility, stability, and biopharmaceutical performance narrow
the selection of excipients, and further technical constraints arise
from needed pharmaceutical processing. The present work introduces
the concept of molecularly targeted interactions of a coformer with
a polymer to design a new matrix for HME. Model systems of dimethylaminoethyl
methacrylate copolymer, Eudragit E (EE), and bicarboxylic acids were
studied, and pronounced molecular interactions were demonstrated by 1H, 13C NMR, FTIR spectroscopy, as well as by different
techniques of microscopic imaging. A difference was shown between
new formulations exploiting specifically the targeted molecular interactions
and a common drug–polymer formulation. More specifically, a
modified matrix with malic acid exhibited a technical extrusion advantage
over polymer alone, and there was a benefit of improved physical stability
revealed for the drug fenofibrate. This model compound displayed greatly
enhanced dissolution kinetics from the ASD formulations. It can be
concluded that harnessing molecularly designed polymer modifications
by coformers has much potential in solid dispersion technology and
in particular regarding HME processing.
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