Indomethacin (IM) is a small molecule active pharmaceutical ingredient (API) that exhibits polymorphism with the γ-form being the most thermodynamically stable form of the drug. The α-form is metastable, but it exhibits higher solubility, making it a more attractive form for drug delivery. As with other metastable polymorphs, α-IM undergoes interconversion to the stable form when subjected to certain stimuli, such as solvent, heat, pH, or exposure to seed crystals of the stable form. In this study, IM was crystallized into cellulose nanocrystal aerogel scaffolds as a mixture of the two polymorphic forms, α-IM and γ-IM. Differential scanning calorimetry (DSC) and Raman spectroscopy were used to quantitatively determine the amount of each form. Our investigation found that the metastable α-IM could be stabilized within the aerogel without phase transformation, even in the presence of external stimuli, including heat and γ-IM seed crystals. Because interconversion is often a concern during production of metastable forms of APIs, this approach has important implications in being able to produce and stabilize metastable drug forms. While IM was used as a model drug in this study, this approach could be expanded to additional drugs and provide access to other metastable API forms.
Last. Lu Lin(Ha Tai: Xiamen University)H-Index: 44
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Abstract Natural cellulose is a kind of both traditional and emerging multifunctional material with high surface area, high strength, flexibility, and tunable surface chemistry, intensifying the quest for various products with properties that can mimic natural designs, functions, and properties in biomaterials, cosmetics, and food products. This review summarizes the modification methods of cellulose, preparation methods, physical and chemical properties and the possible applications of cellulos...
Abstract Cellulose was and still is the most abundant biopolymer generated from all plant fibers including agricultural wastes. Using this waste as a starting material in the production of new products is a field of great interest. The demand for renewable and available resources in combination with advanced technologies is a necessity to develop new generations of advanced nanomaterials. This review aims to present integrated details on the extraction techniques and structure of nanofibrillated...
Cellulose nanocrystals (CNCs) are attractive for use in polymer composites, biomedical applications, and barrier packaging. In all of these applications they are mixed with other components and compatibility is a major design consideration, as CNCs naturally have a high density of surface hydroxyl groups and primarily disperse well in polar media. Numerous surface modification approaches have been used to address these issues, but challenges remain due to the variability in the commercially avai...
Polymorphism is the ability of solid materials, including active pharmaceutical ingredients (APIs), to exist in structurally distinctive arrangements. The existence of polymorphism and the difference in molecular packing can cause crystals to have a variety of different physical properties. Therefore, the ability to experimentally control and predict polymorph formation is vital to gain consistent access to desired properties of APIs. In this study, polymorphic control of the metastable form II ...
The crystallisation of metastable drug polymorphs in polymer matrices has been reported as a successful approach to enhance the solubility of poorly water-soluble drug molecules. This can be achieved using different polymers, drug to polymer ratios and formulation techniques enabling the formation of stable nuclei and subsequent growth of new or metastable drug polymorphs. In this work we elucidated the polymorphism behaviour of a model compound fluconazole (FLU) embedded in solid dispersions wi...
The crystallization of seven active pharmaceutical ingredients (APIs) (acetaminophen (AAP), carbamazepine (CBMZ), caffeine (CAF), phenylbutazone (PBZ), risperidone (RIS), clozapine base (CPB), and fenofibrate (FF)) was studied in the absence and presence of microcrystalline cellulose (MCC) which acted as a heterosurface. Two of the active pharmaceutical ingredients (APIs), namely, AAP and CBMZ, possess hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) functionalities, whereas the other ...
#1Lucrèce Nicoud(MIT: Massachusetts Institute of Technology)H-Index: 10
#2Filippo Licordari(MIT: Massachusetts Institute of Technology)H-Index: 2
Last. Allan S. Myerson(MIT: Massachusetts Institute of Technology)H-Index: 46
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Solubility measurements of metastable polymorphs are often complicated by solvent-mediated transformation toward more stable forms. In this review, we first summarize potential experimental methods to estimate the solubility of metastable polymorphs. Then, we discuss a methodology based on a thermodynamic model, which allows solubility predictions from (i) solubility data of the stable form, and (ii) solid-state properties of the stable and metastable forms.
#1Fiora Artusio(Polytechnic University of Turin)H-Index: 3
#2Roberto Pisano(Polytechnic University of Turin)H-Index: 22
Abstract Despite the wide occurrence of crystallization in the pharmaceutical industry, deep understanding and fine control of the process remain a tricky issue. Nevertheless, the successful manufacturing of finished pharmaceutical products, as well as the structural determination of biopharmaceuticals, depend on the size, form, shape and purity of the crystals. The ability of substrates with precise chemistry and topological features to induce nucleation has been thoroughly assessed during the ...
Purpose To study and elucidate the effect of the intensity and duration of processing stresses on the possible solid-state changes during a hot melt extrusion granulation process.
The crystallization of metastable crystal polymorphs in polymer matrices has been extensively reported in literature as a possible approach to enhance the solubility of poorly water-soluble drug compounds, yet no clarification of the mechanism of the polymorph formation has been proposed. The current work aims to elucidate the polymorphism behavior of the model compound indomethacin as well as the mechanism of polymorph selection of drugs in semicrystalline systems. Indomethacin crystallized as ...