Enhancing the solubility and permeability of the diuretic drug furosemide via multicomponent crystal forms

Diniz, Luan F.; Carvalho, Paulo S.; Pena, Sarah A.C.; Gonçalves, José Eduardo; Souza, Mateus Araújo Castro e; Filho, José Dias de Souza; Filho, Lucius F.O. Bomfim; Franco, Chris H. J.; Diniz, Renata; Fernandes, Christian

doi:10.1016/j.ijpharm.2020.119694

Cited by 21 publications

(18 citation statements)

References 50 publications

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“…Compared with the commercial form-I, the above results demonstrate that the permeability of novel ETP form-II is superior to that of the marketed form-I. Permeability of the commercial form-I is lower than that of the other polymorphs, and this observation prompts further studies to enhance not just solubility/dissolution but also drug permeability/flux pass in pharmaceutical crystal forms. − …”

Section: Resultsmentioning

confidence: 89%

Entacapone Polymorphs: Crystal Structures, Dissolution, Permeability, and Stability

Bommaka

Mannava

Sunil

et al. 2021

Crystal Growth & Design

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Entacapone (ETP) is a catechol-O-methyltransferase (COMT) drug used to treat Parkinson’s disease. ETP is available in the marketplace under the brand name Comtan since 2010, and ETP form-I was first reported in a patent published in 2001. However, analysis of its X-ray crystal structures and stability relationship of ETP polymorphs and their dissolution and permeability profile have not yet been reported. We crystallized two new conformational polymorphs of ETP from a water and acetone mixture and studied the structural origin of polymorphism and their phase transformations, stability, equilibrium solubility, dissolution, and permeability properties. The ETP molecule adopts different conformations in the polymorphic structures with slight changes in carbonyl and nitrile group orientations. Thermal analysis suggests that form-III and form-IV are enantiotropically related to form-I, which is the thermodynamically stable form at ambient conditions. In contrast, form-II is monotropically related to form-I. Equilibrium solubility, dissolution, and permeability studies show that form-II persists in the slurry medium and dissolves faster with a high flux rate compared to the stable form-I in phosphate buffer solution at 37 ± 0.5 °C.

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Section: Resultsmentioning

confidence: 89%

Entacapone Polymorphs: Crystal Structures, Dissolution, Permeability, and Stability

Bommaka

Mannava

Sunil

et al. 2021

Crystal Growth & Design

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show abstract

“…1b). Along [001] direction, adjacent chains are held together through the R 2 2 (8) homo-dimetric motif between the MET + cations related by an inversion center. Thus, a 2D-sheet is formed positioning the MAL À anions out of this arrangement (Fig.…”

Section: Crystallographic Descriptionmentioning

confidence: 99%

“…inclusion of complementary molecules (coformers) in the crystal lattice without breaking covalent bonds, preserves the inherent drug activities and further provides novel active pharmaceutical ingredients (APIs) with enhanced physicochemical properties. [5][6][7][8] Within this framework, salt formation has consolidated itself as the most effective and low-cost method and consequently the preferential one to optimize the drug's biopharmaceutical features (aqueous solubility, dissolution rate, permeability, and bioavailability). [9][10][11] Overall, pharmaceutically acceptable and low-toxic acids are used as coformers to protonate a basic drug, such as metformin (MET, Scheme 1), and thereby convert it into novel suitable salts.…”

Section: Introductionmentioning

confidence: 99%

Solid-state landscape and biopharmaceutical implications of novel metformin-based salts

et al. 2022

Self Cite

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“…Several authors have reported pharmaceutical salts and cocrystals of FUR. A search of this dataset for drug-drug multi-component crystals revealed a total of 11 systems [8,[10][11][12][13][29][30][31]. A common structural feature observed is the key role of the carboxylic group in the interaction with the coformer or counterion and the formation of other synthons involving the sulfonamide group that participates in stabilizing the crystal structure packing.…”

Section: Coformer Selectionmentioning

confidence: 99%

“…The development of this novel strategy is rather interesting because allows industry to save money compared to the traditional drug development scheme, still guarantying the possibility of generating intellectual property rights [7]. In this context, there has been reported several studies devoted to studying pharmaceutical cocrystals and salts of furosemide [8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Furosemide/Non-Steroidal Anti-Inflammatory Drug–Drug Pharmaceutical Solids: Novel Opportunities in Drug Formulation

et al. 2021

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The design of drug–drug multicomponent pharmaceutical solids is one the latest drug development approaches in the pharmaceutical industry. Its purpose is to modulate the physicochemical properties of active pharmaceutical ingredients (APIs), most of them already existing in the market, achieving improved bioavailability properties, especially on oral administration drugs. In this work, our efforts are focused on the mechanochemical synthesis and thorough solid-state characterization of two drug–drug cocrystals involving furosemide and two different non-steroidal anti-inflammatory drugs (NSAIDs) commonly prescribed together: ethenzamide and piroxicam. Besides powder and single crystal X-ray diffraction, infrared spectroscopy and thermal analysis, stability, and solubility tests were performed on the new solid materials. The aim of this work was evaluating the physicochemical properties of such APIs in the new formulation, which revealed a solubility improvement regarding the NSAIDs but not in furosemide. Further studies need to be carried out to evaluate the drug–drug interaction in the novel multicomponent solids, looking for potential novel therapeutic alternatives.

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Enhancing the solubility and permeability of the diuretic drug furosemide via multicomponent crystal forms

Cited by 21 publications

References 50 publications

Entacapone Polymorphs: Crystal Structures, Dissolution, Permeability, and Stability

Entacapone Polymorphs: Crystal Structures, Dissolution, Permeability, and Stability

Solid-state landscape and biopharmaceutical implications of novel metformin-based salts

Furosemide/Non-Steroidal Anti-Inflammatory Drug–Drug Pharmaceutical Solids: Novel Opportunities in Drug Formulation

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