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

Nugrahani, Ilma; Fisandra, Felicia; Horikawa, Ayano; Uekusa, Hidehiro

doi:10.1016/j.xphs.2021.05.022

Cited by 7 publications

(3 citation statements)

References 57 publications

(70 reference statements)

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“…The spectra of the AntiY 5 R-NaTC preparations showed a similar spectral pattern to that of AntiY 5 R, but the peak derived from the S=O of sulfonamide for AntiY 5 R shifted from 1358 cm −1 to 1375 cm −1 , while the peak derived from the S=O of sulfonate for NaTC shifted from 1169 cm −1 to 1163 cm −1 as the molar ratio of NaTC increased in the co-amorphous system. It was previously reported that Na + could interact with other molecules in addition to the molecule with which Na + forms the sodium salt [ 60 ]. Moreover, AntiY 5 R and NaTC are not able to form salts based on the calculated pKa values because their ∆pKa (∆pKa = pKa (base) − pKa (acid)) value is lower than 3 [ 61 ].…”

Section: Resultsmentioning

confidence: 99%

Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature

et al. 2022

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Brick dust molecules are usually poorly soluble in water and lipoidal components, making it difficult to formulate them in dosage forms that provide efficient pharmacological effects. A co-amorphous system is an effective strategy to resolve these issues. However, their glass transition temperatures (Tg) are relatively lower than those of polymeric amorphous solid dispersions, suggesting the instability of the co-amorphous system. This study aimed to formulate a stable co-amorphous system for brick dust molecules by utilizing sodium taurocholate (NaTC) with a higher Tg. A novel neuropeptide Y5 receptor antagonist (AntiY5R) and NaTC with Tg of 155 °C were used as the brick dust model and coformer, respectively. Ball milling formed a co-amorphous system for AntiY5R and NaTC (AntiY5R-NaTC) at various molar ratios. Deviation from the theoretical Tg value and peak shifts in Fourier-transform infrared spectroscopy indicated intermolecular interactions between AntiY5R and NaTC. AntiY5R-NaTC at equal molar ratios resulting in an 8.5-fold increase in AntiY5R solubility over its crystalline form. The co-amorphous system remained amorphous for 1 month at 25 °C and 40 °C. These results suggest that the co-amorphous system formed by utilizing NaTC as a coformer could stably maintain the amorphous state and enhance the solubility of brick dust molecules.

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Section: Resultsmentioning

confidence: 99%

Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature

et al. 2022

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“…One of the recent strategies applied to enhance physicochemical properties of active pharmaceutical compounds is by forming a multi-component crystal phase with an inert and safe coformer. This approach has shown successful improvement in solubility, dissolution rate, physical and chemical stability, and compressibility [6], [7], [8], [9], [10]. Multicomponent crystal phase between active pharmaceutical compounds and coformers could be formed due to non-covalent intermolecular interactions such as van der Waals bonds and hydrogen bonds [11].…”

Section: Introductionmentioning

confidence: 99%

Multicomponent Crystal of Trimethoprim and Citric Acid: Solid State Characterization and Dissolution Rate Studies

Umar

Farnandi

Salsabila

et al. 2022

Open Access Maced J Med Sci

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BACKGROUND: Trimethoprim is a broad spectrum antimicrobial agent with low solubility in water which causes low bioavailability in systemic circulation. AIM: The purpose of this study was to prepare multicomponent crystals of trimethoprim and citric acid to increase the solubility and dissolution rate of trimethoprim. MATERIALS AND METHODS: Multicomponent crystals were prepared by solvent evaporation method. Characterizations of multicomponent crystalline solid phase properties were carried out by powder X-ray diffraction (PXRD) analysis, differential scanning calorimetry (DSC), FT-IR spectroscopy, scanning electron microscopy (SEM). Solubility and dissolution rate tests were carried out in aqueous medium. RESULTS: The PXRD characterization results showed a new X-ray diffraction pattern in the multicomponent crystal phase. DSC analysis showed the formation of a new endothermic peak. This indicates the formation of a multicomponent crystal phase between trimethoprim and citric acid. The results of the SEM analysis indicate the formation of a new crystal habit. Solubility of multi-component crystal phase of trimethoprim increased 7 times compared to intact trimethoprim. The dissolution of trimethoprim and multicomponent crystals in 0.1 N HCl medium at 60 minutes was 56.36% and 95.57% and CO2-free distilled water medium was 43.03% and 88.26%, respectively. CONCLUSIONS: From the results of the study, it can be concluded that the multicomponent phase of trimethoprim crystals with citric acid successfully increase the solubility and dissolution rate of trimethoprim significantly.

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“…Many times, undesired technical properties can hinder the market of a drug with suitable pharmacokinetics and pharmacodynamics, and the correct choice of a solid form rises as the only alternative to overcome them. Flowability, compactability, compressibility, tablet ability, and hygroscopicity are some examples of technical properties defining certain crystal forms to be marketed. − Nowadays, the investigation of how drug technical characteristics can be modulated by the structure and presence of coformers in the solid state goes beyond the academy. Many patents of technically improved drug crystal forms have been deposited by great pharmaceutical companies, such as Pfizer, AstraZeneca, Novartis, Abbott, among others. − …”

Section: Introductionmentioning

confidence: 99%

New Multicomponent Crystal Forms of Adiphenine with Low Hygroscopicity

Ribeiro

Silva

Neto

et al. 2022

Crystal Growth & Design

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Adiphenine is an acetylcholine receptor inhibitor used as an antispasmodic drug due to its strong smooth muscle relaxant action. Adiphenine hydrochloride is largely marketed in drug associations to treat muscle spasms and relieve pain in colic and cramps. However, it presents serious problems with hygroscopicity and chemical stability under high humidity conditions, which have limited its use as an active pharmaceutical ingredient (API). Here, we have solved the adiphenine solid-state hygroscopicity problem through the preparation of stable, nonhygroscopic multicomponent crystal forms thereof. Two new salts of adiphenine were designed by recognition of intermolecular interaction patterns in the Cambridge Structural Database (CSD) and ΔpK a rules. Two generically recognized as safe (GRAS) coformers, namely, citric acid and oxalic acid, were chosen and formed monobasic salts with adiphenine. Crystal structure elucidation reveals that adiphenine adopts different conformations in our salts, while in the literature, hydrochloride adopts one, which is related to different intermolecular arrays. In the dynamic vapor sorption (DVS) analysis, it was verified that adiphenine citrate and adiphenine oxalate starts to incorporate water slowly from 50 to 70% of relative humidity (RH), increasing up to 3.2 and 2.6% of their initial masses in 90% of RH, respectively. At the end of the desorption cycle (RH = 0%), the samples retained only 0.12 and 0.08% of water relative to their initial masses. On the other hand, adiphenine hydrochloride exhibits a classical high hygroscopicity behavior, which retains water fast from 50% of relative humidity (RH), increasing up to 22% of its initial mass in 90% of RH and a net mass gain of 5% at the end of the desorption cycle (RH = 0%). Notably, both carboxylic acid salts had similar solubility as a function of medium pH, while the hydrochloride one was more soluble than them by factors ranging from 6.7 (relative to citrate in pH 1.2) to 28.2 (relative to oxalate in pH 4.5). Nevertheless, the pharmacokinetic parameters of adiphenine after oral administration of the capsules containing the salt forms did not reflect these solubility differences, since all adiphenine salt forms can be considered highly soluble drugs according to the Biopharmaceutics Classification System (dose/solubility ratio < 250 mL). It was observed that the rats treated with capsules containing adiphenine hydrochloride had an increase in AUC 0−∞ (1537 vs 914 vs 991 min μg mL −1 ) compared with rats treated with adiphenine citrate and oxalate capsules, respectively, even though the same t max (48 min) was observed. However, dosage tuning can bring the bioavailability of our salts into that of the hydrochloride salt, with the advantage of nonhygroscopicity and higher chemical stability.

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

Cited by 7 publications

References 57 publications

Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature

Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature

Multicomponent Crystal of Trimethoprim and Citric Acid: Solid State Characterization and Dissolution Rate Studies

New Multicomponent Crystal Forms of Adiphenine with Low Hygroscopicity

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