Skip to Content
MilliporeSigma
  • Salt stability--effect of particle size, relative humidity, temperature and composition on salt to free base conversion.

Salt stability--effect of particle size, relative humidity, temperature and composition on salt to free base conversion.

Pharmaceutical research (2014-08-26)
Yi-Ling Hsieh, Lynne S Taylor
ABSTRACT

The aim of this study was to investigate how factors such as temperature, relative humidity and particle size impact the extent of disproportionation (salt to free base conversion) in powder blends of miconazole, benzocaine or sertraline mesylate salts mixed with a basic additive. Raman spectroscopy was used to quantitate the extent of disproportionation. The data was further analyzed by multivariate analysis with partial least squares (PLS) modeling. It was found that salt disproportionation was significantly influenced by % weight gain due to moisture sorption both in terms of the kinetics and the conversion extent, suggesting a solution-mediated reaction. Temperature plays an important role in impacting the value of pHmax which in turn has a significant correlation to the amount of free base formed. The particle size and drug: additive ratio were also found to influence the extent of disproportionation. This study shows that the extent of salt disproportionation is influenced by multiple factors and the application of PLS modeling demonstrated the feasibility of utilizing multivariate analysis to generate a predictive model for estimating the extent of conversion and thus may serve as a tool for risk assessment.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Magnesium chloride hexahydrate, tested according to Ph. Eur.
Sigma-Aldrich
Magnesium chloride hexahydrate, BioReagent, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Magnesium chloride hexahydrate, BioUltra, Molecular Biology, ≥99.0% (KT)
Sigma-Aldrich
Magnesium chloride hexahydrate, ReagentPlus®, ≥99.0%
Sigma-Aldrich
Magnesium chloride hexahydrate, BioXtra, ≥99.0%
Sigma-Aldrich
Magnesium chloride hexahydrate, 99.995% trace metals basis
Sigma-Aldrich
Magnesium chloride hexahydrate, meets USP testing specifications
Sigma-Aldrich
Magnesium chloride hexahydrate, BioUltra, ≥99.0% (KT)
Sigma-Aldrich
Ethyl 4-aminobenzoate, 98%
Sigma-Aldrich
Magnesium chloride hexahydrate, ACS reagent, 99.0-102.0%
Sigma-Aldrich
Magnesium chloride hexahydrate, puriss., meets analytical specification of Ph. Eur., BP, FCC, E511, 99-101%, ≤0.0001% Al
Miconazole, European Pharmacopoeia (EP) Reference Standard
USP
Miconazole, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Sodium chloride, JIS special grade, ≥99.5%
Sigma-Aldrich
Sodium chloride, SAJ first grade, ≥99.0%
Sigma-Aldrich
Potassium iodide, JIS special grade, ≥99.5%
Sigma-Aldrich
Sodium chloride solution, 1 M
Sigma-Aldrich
Sodium chloride solution, 0.1 M
Sigma-Aldrich
Cobalt(II) chloride hexahydrate, SAJ first grade, ≥95.0%
Sigma-Aldrich
Cobalt(II) chloride hexahydrate, JIS special grade, ≥99.0%
Sigma-Aldrich
Potassium iodide, SAJ first grade, ≥99.5%
Sigma-Aldrich
Magnesium nitrate hexahydrate, BioUltra, ≥99.0% (KT)
Sigma-Aldrich
Potassium iodide, tested according to Ph. Eur.
Sigma-Aldrich
Sodium chloride, random crystals, 99.9% trace metals basis
Sigma-Aldrich
Potassium iodide, AnhydroBeads, −10 mesh, 99.998% trace metals basis
Sigma-Aldrich
Potassium iodide, suitable for plant cell culture
Sigma-Aldrich
Potassium iodide, BioXtra, ≥99.0%
Sigma-Aldrich
Cobalt(II) chloride hexahydrate, BioReagent, suitable for cell culture, suitable for insect cell culture
SAFC
Sodium chloride solution, 5 M
Sigma-Aldrich
Sodium phosphate tribasic dodecahydrate, ≥98%