The first zwitterionic cocrystal of indomethacin with amino acid showing optimized physicochemical properties as well as accelerated absorption and slowed elimination <i>in vivo</i>

Wang, Ling-Yang; Yu, Yueming; Jiang, Fubin; Li, Yan‐Tuan; Wu, Zhi‐Yong; Yan, Cui‐Wei

doi:10.1039/c9nj06180k

Cited by 28 publications

(20 citation statements)

References 59 publications

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“…The number of hydrogen interactions may represent the solubility of the co-crystals. This phenomenon is supported by the hydrotropic effect of co-formers such as proline (PRO) to dissolve a more hydrophobic API with excellent solubility [ 23 ]. Additionally, co-crystals show increased dissolution, bioavailability, stability, and mechanical properties.…”

Section: Co-crystalmentioning

confidence: 99%

“…For example, a co-crystal consisting of two APIs, namely pyrithyldione as sedative and propyphenazone as NSAID, produces three polymorphs; the polymorph form II was the most stable [ 35 ]. Since then, NSAID co-crystals have continued to develop in terms of screening, manufacturing techniques, and enhancement of physicochemical properties [ 23 , 28 , 36 , 37 , 38 ]. Furthermore, some invented NSAID co-crystals are summarized in Table 1 .…”

Section: Progress On Nsaid Co-crystalsmentioning

confidence: 99%

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Challenges and Progress in Nonsteroidal Anti-Inflammatory Drugs Co-Crystal Development

Nugrahani

Parwati

2021

Molecules

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Co-crystal innovation is an opportunity in drug development for both scientists and industry. In line with the “green pharmacy” concept for obtaining safer methods and advanced pharmaceutical products, co-crystallization is one of the most promising approaches to find novel patent drugs, including non-steroidal anti-inflammatory drugs (NSAID). This kind of multi-component system improves previously poor physicochemical and mechanical properties through non-covalent interactions. Practically, there are many challenges to find commercially viable co-crystal drugs. The difficulty in selecting co-formers becomes the primary problem, followed by unexpected results, such as decreased solubility and dissolution, spring and parachute effect, microenvironment pH effects, changes in instability, and polymorphisms, which can occur during the co-crystal development. However, over time, NSAID co-crystals have been continuously updated regarding co-formers selection and methods development.

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Section: Co-crystalmentioning

confidence: 99%

Section: Progress On Nsaid Co-crystalsmentioning

confidence: 99%

Challenges and Progress in Nonsteroidal Anti-Inflammatory Drugs Co-Crystal Development

Nugrahani

Parwati

2021

Molecules

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“…l -proline is the most soluble amino acid and can dissolve hydrophobic molecules with a hydrotropic effect. In addition, l -proline also supports the permeability properties of API, i.e., indomethacin [ 90 ]. This amino acid builds a flexible but intense interaction with another compound based on a zwitterionic interaction and a rigid structure, which added value for this co-former.…”

Section: Amino Acids As Co-formersmentioning

confidence: 99%

“…From the pharmacokinetic study, the co-crystal showed a maximum concentration that was similar to that of pure indomethacin. However, it was reached in a shorter time, and the level of the co-crystal was higher than the pure compound during the elimination process [ 90 ].…”

Section: Amino Acids As Co-formersmentioning

confidence: 99%

Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review

Nugrahani

Jessica

2021

Molecules

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Co-crystals are one of the most popular ways to modify the physicochemical properties of active pharmaceutical ingredients (API) without changing pharmacological activity through non-covalent interactions with one or more co-formers. A “green method” has recently prompted many researchers to develop solvent-free techniques or minimize solvents for arranging the eco-friendlier process of co-crystallization. Researchers have also been looking for less-risk co-formers that produce the desired API’s physicochemical properties. This review purposed to collect the report studies of amino acids as the safe co-former and explored their advantages. Structurally, amino acids are promising co-former candidates as they have functional groups that can form hydrogen bonds and increase stability through zwitterionic moieties, which support strong interactions. The co-crystals and deep eutectic solvent yielded from this natural compound have been proven to improve pharmaceutical performance. For example, l-glutamine could reduce the side effects of mesalamine through an acid-base stabilizing effect in the gastrointestinal fluid. In addition, some amino acids, especially l-proline, enhances API’s solubility and absorption in its natural deep eutectic solvent and co-crystals systems. Moreover, some ionic co-crystals of amino acids have also been designed to increase chiral resolution. Therefore, amino acids are safe potential co-formers, which are suitable for improving the physicochemical properties of API and prospective to be developed further in the dosage formula and solid-state syntheses.

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“…Thus, IMC shows low bioavailability and, to be effective, requires special manufacturing and increased dosage, which in turn may worsen adverse effects such as gastric irritation or renal malfunctioning. 3,8 Schemes for enhancing IMC dissolution rate and intestinal absorption include the crystallization of IMC as co-crystals, [8][9][10][11][12] salts 13 and solvates, 14,15 or its administration together with physiologic buffers or emulsions that modify the local pH. 16,17 The aqueous solubility of IMC is mainly driven by the ionization of its carboxylic group and hence it is freely soluble at pH > 4.5.…”

Section: Introductionmentioning

confidence: 99%

Structure Determination, Thermal Stability and Dissolution Rate of δ Indomethacin

Andrusenko¹,

Hamilton²,

Lanza³

et al. 2021

Preprint

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<div> <p>The structure solution of the δ-polymorph of indomethacin was obtained using three-dimensional electron diffraction. This form shows a significantly enhanced dissolution rate compared with the more common and better studied α- and γ-polymorphs, indicating an increased bioavailability for medicinal applications. The structure was solved in non-centrosymmetric space group <i>P</i>2<sub>1</sub> and comprises two molecules in the asymmetric unit. Packing and molecule conformation closely resemble indomethacin methyl ester and indomethacin methanol solvate. Knowledge of the structure allowed the rational interpretation of spectroscopic IR and Raman data for δ-polymorph and a tentative interpretation for still unsolved indomethacin polymorphs. Finally, we observed a solid-solid transition from δ-polymorph to α-polymorph that can be driven by similarities in molecular conformation.</p> </div> <br>

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The first zwitterionic cocrystal of indomethacin with amino acid showing optimized physicochemical properties as well as accelerated absorption and slowed elimination in vivo

Abstract: The first zwitterionic cocrystal of indomethacin (INC) with proline (PL) with optimized in vitro/in vivo properties was prepared and characterized.

Cited by 28 publications

References 59 publications

Challenges and Progress in Nonsteroidal Anti-Inflammatory Drugs Co-Crystal Development

Challenges and Progress in Nonsteroidal Anti-Inflammatory Drugs Co-Crystal Development

Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review

Structure Determination, Thermal Stability and Dissolution Rate of δ Indomethacin

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