Counterion Quantification for Discovery Chemistry and Pre-Formulation Salt Screening

Reilly, John M.; Wright, Penny; Larrow, Jay F.; Mann, Thierry; Twomey, Joseph; Grondine, Melissa; Dodd, Stephanie; Capacci-Daniel, Christina; Bilotta, Jennifer; Shah, Lipa; Towler, Christopher

doi:10.1080/10826076.2011.615090

Cited by 5 publications

(1 citation statement)

References 3 publications

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“…The choice of salt-forming reagents usually depends on various factors (Paulekuhn et al, 2007). The primary factor taken into consideration is that the salification process would produce a highly crystalline solid, which will provide an effective means of purification and removal of the undesirable impurities (Reilly et al, 2012). Other important aspects include the consideration of the acidity (or the basicity) of the saltforming reagents, chemical stability, solubility and dissolution rate.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular structures and physicochemical properties of norfloxacin salts

Jiang

Mei

2014

Acta Crystallogr Sect B

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Seven new molecular salts of norfloxacin (1-ethyl-6-fluoro-4-oxo-7-piperazin-1-yl-1H-quinoline-3-carboxylic acid; abbreviated as NF) with various organic acids (adipic acid, mucic acid, o-OH-benzoic acid, m-OH-benzoic acid, p-OH-benzoic acid, naphthalene-1, 5-disulfonic acid and naphthalene-2-sulfonic acid) were synthesized and their crystal structures were determined by X-ray crystallography. Supramolecular structures and reccurring packing patterns are discussed to understand the influence of non-covalent interactions in determination of the crystal packing and hydrate inclusion. The formation of hydrates was commonly observed among various NF salts, except for the adipate salt which exists as an anhydrous form. The physicochemical properties of salts were fully characterized with a variety of analytical techniques, including powder X-ray diffraction (PXRD), Fourier transform IR (FT-IR), Raman spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), hot-stage microscopy (HSM) and dynamic vapour sorption (DVS) etc. The synthesized norfloxacin salts were found to have different physicochemical properties, superior solubility and hygroscopicity. Particularly, NF adipate was found to be a desirable candidate for further development.

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Section: Introductionmentioning

confidence: 99%

Supramolecular structures and physicochemical properties of norfloxacin salts

Jiang

Mei

2014

Acta Crystallogr Sect B

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Salt Screening and Selection

Tian

Reid

Semin

2021

Burger's Medicinal Chemistry and Drug Discovery

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The stability, processability, and in vivo performance of active pharmaceutical ingredients (APIs) are significantly affected by their salt forms. The appropriate salt can improve the overall therapeutic and pharmaceutical performance of an API. Salt screening and selection is integrated into the drug discovery and development, and the desired attributes are impacted by multiple factors, including API chemistry, the intended dosage form, pharmacokinetics, and pharmacodynamics. Counterion, solvent, and crystallization are three key elements affecting screening outcomes and selection of the final salt form. Common applications of pharmaceutical salts, general considerations for using salt forms, and a brief acid–base theory related to solubility estimation for salt forms are introduced. A strategy to select counterions and solvents for salt formation is articulated in detail as well as crystallization methodology to harvest highly pure and crystalline salt forms. Three different salt‐screening approaches ( in situ , rational, and high throughput) are discussed with respect to resource required, project timelines, and the purpose of the study. A four‐tier salt selection strategy is presented, and the desired attributes to meet the target product profile for a typical oral drug are included to guide selection of an appropriate salt from the very initiation of form screen.

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