Crystalline palmatine saccharinate pharmaceutical salt without reducing solubility and improving its hygroscopic stability with regard to palmatine chloride

Zhang, Yunan; Zhang, Yanfei; Chang, Liang; Ji, Yuanyuan; Liu, Lixin; Feng, Yanru; Wu, Lili; Zhang, Lei; Zou, Dongyu; Liu, Yingli; Su, Xin

doi:10.1016/j.molstruc.2020.129631

Cited by 10 publications

(6 citation statements)

References 24 publications

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“…Although the novel salt form exhibited low hygroscopicity, the solubility of the salt form was reduced [ 19 ]. A similar observation was noted with the palmatine saccharinate salt and gallic acid-palmatine chloride co-crystal, which showed better hygroscopic stability but reduced its aqueous solubility [ 23 , 35 ]. Another study by Ribeiro et al [ 15 ] aimed at reducing the hygroscopicity of adiphenine hydrochloride by preparing more stable oxalate and citrate salt forms.…”

Section: Moisture Interaction With Solidsupporting

confidence: 69%

“…The hygroscopic APIs mainly interact with the water molecules through intermolecular hydrogen bonding. The hygroscopic materials, such as berberine chloride [ 33 ], theophylline [ 34 ], palmatine chloride [ 35 ], oxymatrine [ 36 ], etc., have several hydrogen bond donors or acceptors in their chemical structure that are involved in the hydrogen bonding with the atmospheric moisture and thereby facilitate adsorption and subsequent ingress of water into the crystal lattice of these molecules. Depending upon the type of hydrogen bonding site (-OH, -COOH, -NH, -X, etc.)…”

Section: Moisture Interaction With Solidmentioning

confidence: 99%

“…The following examples support the aforesaid statement. Berberine chloride (BCl) and palmatine chloride are the major alkaloidal compounds used in herbal preparations [ 16 , 23 , 35 , 40 ]. The hydrochloride salt forms of both compounds are hygroscopic but their other salt forms and co-crystals are relatively less hygroscopic in nature.…”

Section: Moisture Interaction With Solidmentioning

confidence: 99%

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Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

et al. 2023

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Stability is an essential quality attribute of any pharmaceutical formulation. Poor stability can change the color and physical appearance of a drug, directly impacting the patient’s perception. Unstable drug products may also face loss of active pharmaceutical ingredients (APIs) and degradation, making the medicine ineffective and toxic. Moisture content is known to be the leading cause of the degradation of nearly 50% of medicinal products, leading to impurities in solid dose formulations. The polarity of the atoms in an API and the surface chemistry of API particles majorly influence the affinity towards water molecules. Moisture induces chemical reactions, including free water that has also been identified as an important factor in determining drug product stability. Among the various approaches, crystal engineering and specifically co-crystals, have a proven ability to increase the stability of moisture-sensitive APIs. Other approaches, such as changing the salt form, can lead to solubility issues, thus making the co-crystal approach more suited to enhancing hygroscopic stability. There are many reported studies where co-crystals have exhibited reduced hygroscopicity compared to pure API, thereby improving the product’s stability. In this review, the authors focus on recent updates and trends in these studies related to improving the hygroscopic stability of compounds, discuss the reasons behind the enhanced stability, and briefly discuss the screening of co-formers for moisture-sensitive drugs.

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Section: Moisture Interaction With Solidsupporting

confidence: 69%

Section: Moisture Interaction With Solidmentioning

confidence: 99%

Section: Moisture Interaction With Solidmentioning

confidence: 99%

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Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

et al. 2023

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“…Palmatine chloride is composed of one quaternary ammonium cation and one chloride anion (Scheme ). Until now, some organic salts of palmatine have been reported, , while pharmaceutical cocrystals of palmatine chloride have not been well exploited due to a lack of reliable supramolecular synthons. In fact, chloride ion is a typical, but less used, hydrogen bond acceptor.…”

Section: Introductionmentioning

confidence: 99%

Two Cocrystal Polymorphs of Palmatine Chloride with Racemic Hesperetin

Zhang

Liu

et al. 2021

Crystal Growth & Design

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Two polymorphic cocrystals of palmatine chloride with racemic hesperetin (Form I and Form II) have been prepared and investigated systematically. Crystal structure analysis reveals that reliable O-H•••Cl − hydrogen-bonding interactions exist in both cocrystal polymorphs. However, similar O-H•••Cl − hydrogen-bonding interactions resulted in completely different supramolecular arrangements. Cocrystal Forms I and II are non-hygroscopic and show high stability against temperature, humidity, and light. The cocrystal formation greatly lowers the solubility of palmatine chloride, while the solubility of hesperetin has been improved. Sustained release of palmatine chloride and enhanced release of hesperetin from two cocrystal polymorphs in pure water were achieved.

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“…A significant increase in the solubility of these salts was indicated with compared to the solubility of the drug substance. On the other hand, there are numerous salts of saccharin with active pharmaceutical ingredients, such as quinine, haloperidol, mirtazapine, pseudoephedrine, lamivudine, risperidone, sertraline, venlafaxine, zolpidem and amlodipine [ 18 ], sulfamethazine [ 19 ], stanozolol [ 20 ], lamotrigine [ 21 ], trospium [ 22 ], diphenhydramine [ 23 ], ciprofloxacin [ 24 ], and palmatine [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

New Saccharin Salt of Chlordiazepoxide: Structural and Physicochemical Examination

Lech

Garbacz

Sikorski

et al. 2022

IJMS

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Since the formation of organic salts can improve the solubility, bioavailability, and stability of active pharmaceutical ingredients, the aim of this work was to prepare an organic salt of chlordiazepoxide with saccharin. To achieve this goal, the saccharin salt of chlordiazepoxide was obtained from a physical mixture of both components by grinding them with a small volume of solvent and by crystallizing them with complete evaporation of the solvent. The resulting salt was examined by methods such as Powder X-ray Diffraction (PXRD), Single Crystal X-ray Diffraction (SCXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FT-IR), and Raman spectroscopy. The results of the studies proved that saccharin salt of chlordiazepoxide crystallizes in the orthorhombic Pbca space group with one chlordiazepoxide cation and one saccharin anion in the asymmetric unit. In the crystal of the title compound, the chlordiazepoxide cation and the saccharin anion interact through strong N–H…O hydrogen bonds and weak C–H…O hydrogen bonds. The disappearance of the N–H band in the FT-IR spectrum of saccharin may indicate a shift of this proton towards chlordiazepoxide, while the disappearance of the aromatic bond band in the chlordiazepoxide ring in the Raman spectrum may suggest the formation of intermolecular hydrogen bonds between chlordiazepoxide molecules. The melting point of the salts differs from that of the starting compounds. Thermal decomposition of the salt begins above 200 °C and shows at least two overlapping stages of mass loss. In summary, the results of the research showed that the crystalline salt of the saccharin and chlordiazepoxide can be obtained by various methods: grinding with the addition of acetonitrile and crystallization from acetonitrile or a mixture of methanol with methylene chloride.

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Crystalline palmatine saccharinate pharmaceutical salt without reducing solubility and improving its hygroscopic stability with regard to palmatine chloride

Cited by 10 publications

References 24 publications

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

Two Cocrystal Polymorphs of Palmatine Chloride with Racemic Hesperetin

New Saccharin Salt of Chlordiazepoxide: Structural and Physicochemical Examination

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