Composing Novel Diclofenac Potassium and l-Proline Salt Cocrystal as a Strategy to Increase Solubility and Dissolution

Parwati

2021

Molecules

Self Cite

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.

Section: Progress On Nsaid Co-crystalsmentioning

confidence: 99%

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

Parwati

2021

Molecules

Self Cite

“…The form of the new phase can be distinguished based on the shape of the phase diagram ( Figure 4 ) [ 7 ]. Nugrahani et al used thermal analysis through the construction of the melting point versus the composition of diclofenac sodium/potassium hydrate and l -proline to determine which ratio could form a salt co-crystal [ 22 , 85 ]. The co-crystal will compose a ‘W’ shape on the phase diagram with two eutectic points and one higher melting point between them as shown in Figure 4 c [ 7 , 22 , 85 ].…”

Section: Amino Acids As Co-formersmentioning

confidence: 99%

“…As well as Na + in sodium diclofenac- l -proline salt co-crystal, the K + was a hexa-coordinated structure by two axial water molecules, two connecting water, and two oxygen atoms from the l -proline’s carboxylate group. The presence of water molecules in the hydrate co-crystal structure strengthened each l -proline hydrogen bond, thereby enhancing the interactions in the co-crystal [ 85 ]. These structural features likely improved the physicochemical properties of the API, particularly in dealing with unstable API, such as increasing the stability of highly hygroscopic lactic acid by co-crystallization with tryptophan [ 89 ].…”

Section: Amino Acids As Co-formersmentioning

confidence: 99%

See 1 more Smart Citation

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

Jessica

2021

Molecules

Self Cite

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.

“…42 Moreover, recently, sodium and potassium diclofenac-proline salt cocrystals were proven to enhance diclofenac solubility over alkaline salts and neutral cocrystals. 43,44 NA is a vitamin B3 derivative that is widely used as a safe nutraceutical. This compound is soluble in water and utilized as a coformer for some cocrystals.…”

Section: Introductionmentioning

confidence: 99%

New Sodium Mefenamate – Nicotinamide Multicomponent Crystal Development to Modulate Solubility and Dissolution: Preparation, Structural, and Performance Study

Journal of Pharmaceutical Sciences

Fisandra

Horikawa

et al. 2021

Self Cite

A cocrystal of mefenamic acid (MA) -nicotinamide (NA) has been reported to increase the solubility of MA, but it still does not exceed the solubility of sodium mefenamate (SM). Accordingly, this research dealt with a new salt cocrystal arrangement of SM − NA. Cocrystal screening was performed, followed by powder and single-crystal preparation. Solvent drop grinding and slow evaporation at cold and ambient temperatures were employed to produce the multicomponent crystal. Two new salt cocrystals were found as hemihydrates and monohydrates, named SMN-HH and SMN-MH, respectively. SMN-MH single crystals were successfully isolated and structurally analyzed using a single crystal X-ray diffractometer. Pharmaceutical properties were investigated, including hydrate stability, solubility, and intrinsic dissolution. The experiments showed that the hemihydrate was stable under ambient humidity and temperature, and that the monohydrate rapidly changed to hemihydrate. Both hydrates improved the solubility and intrinsic dissolution of SM, but SMN-HH was superior. The data showed that SMN salt cocrystals combine the advantages of salt and cocrystals and show potential for dosage form development.