An evaluation of salt screening methodologies

Abstract

The three salt formation approaches are methods that deliver crystalline salts. The choice of salt screen approach depends on the physical properties of the drug substance, development stage and objective of the screen.

Improving aqueous solubility of ciprofloxacin: three different stoichiometric hydrated salt forms with oxalic acid

“…7,25 OXA is a dicarboxylic acid that can deprotonate twice, being an oxalate ion with two pK a values; HOOC-COOH ⇌ HOOC-COO − (pK a1 = 1.27) ⇌ − OOC-COO − (pK a2 = 4.3). 26 In accordance with the ΔpK a concept, CIF-OXA has a ΔpK a value greater than 3; thus, the product of CIF-OXA is likely to be a salt. In Table S1, † the blue XRPD pattern of toluene-assisted grinding of CIF-OXA was compared with the green XRPD pattern of methanol-assisted grinding of CIF-OXA.…”

Advanced Methodologies for Pharmaceutical Salt Synthesis

“…The study also underlined difficulties in obtaining salts using APIs that may be soluble in aqueous media. For the screening of water-soluble APIs, the antisolvent-based crystallization process was recommended to induce the production of crystalline salts by precipitation, which is further discussed in the following section …”

“…For the screening of water-soluble APIs, the antisolvent-based crystallization process was recommended to induce the production of crystalline salts by precipitation, which is further discussed in the following section. 64 3.4. Vapor Diffusion with Antisolvent.…”

Application of the solubility parameter concept to assist with oral delivery of poorly water-soluble drugs – a PEARRL review

“…Even though for a single trial, larger amounts of API are required compared to the automated approach a repetition of unsuccessful experiments is avoided. A useful comparison of different screening approaches can be found in the literature for salt selection …”