Salt formation remains the most direct way to change how an API dissolves, stores and processes. We identify the counter-ions that work for your molecule, and tell you which salt is worth developing.
Salt formation is one of the primary solid-state approaches used to modify the physical properties of APIs. A major limitation is that the API must possess a suitable basic or acidic ionisable site. In comparison, co-crystals offer a different pathway where any API — regardless of acidic, basic or ionisable groups — could potentially be co-crystallized.
Where the ionisable site exists, salts are attractive because the effect can be large and the regulatory path is well trodden. A well-chosen counter-ion can raise aqueous solubility by orders of magnitude, improve chemical stability, reduce hygroscopicity, raise the melting point and give a solid that filters, dries and compresses properly.
The counter-ion is not a detail. Two salts of the same molecule can behave so differently that one is developable and the other is not — and each salt brings its own polymorphs, hydrates and solvates. A salt screening is therefore both a search for candidates and an early assessment of the risk each candidate carries.
The work moves from which salts can be formed, to which of them should be.
Confirmation that a suitable acidic or basic site exists, and evaluation of the pKa difference that determines whether a stable salt can realistically form.
A counter-ion list drawn from pharmaceutically accepted acids and bases, sized to the material available and weighted toward those with the best regulatory precedent.
Measurement of how much each salt actually improves solubility and dissolution rate, and whether the gain persists across physiologically relevant pH.
Moisture uptake behaviour, which frequently decides between two otherwise comparable salts — a deliquescent salt is a manufacturing problem regardless of its solubility.
Each promising salt is screened for its own crystal forms, because a salt that exists in several polymorphs inherits all the risks of a polymorphic free base.
A comparative assessment of the candidates against your target profile, so that selection is made on evidence rather than on the first salt that crystallized.
A salt screening is a comparison exercise, so the experimental design is built to make the candidates genuinely comparable.
The free acid or base is characterized first — crystallinity, thermal behaviour, solubility, purity — to give the baseline every salt will be measured against.
Counter-ions are selected on pKa considerations, toxicological acceptability and regulatory precedent, and the list is agreed with you before work starts.
Salt formation is attempted across solvents, stoichiometries and crystallization modes, in parallel, so that a negative result reflects the chemistry rather than a single unlucky condition.
Solids recovered are analysed by diffraction and thermal methods to establish which are genuine crystalline salts rather than mixtures or amorphous precipitates.
Confirmed salts are characterized thermally, spectroscopically and gravimetrically, and their stoichiometry and solvation state determined.
Solubility, dissolution, hygroscopicity, physical and chemical stability are measured side by side across the candidates and against the free form.
The leading salts are screened for their own crystal forms, so that the selected salt does not turn into a polymorphism problem later.
A technical-scientific report with the full data set and a reasoned recommendation on the salt to progress.
Salt characterization draws on the full solid-state laboratory, because stoichiometry, ionisation state and crystal form all have to be established independently.
The study is delivered as a detailed technical-scientific report, structured so that the salt selection decision can be defended to a regulator.
Salt formation is not available, but co-crystallization is, and it can deliver comparable improvements in solubility and processability. Amorphous solid dispersion is the other route. We would normally discuss both with you.
In practice, yes — but on the selected salt rather than on everything. Salts are as polymorphic as free forms, and a salt chosen without a form screening can still surprise you during scale-up. We usually run a focused screening on the one or two leading candidates.
On three criteria: whether the pKa difference supports stable salt formation, whether the counter-ion is pharmaceutically acceptable at the projected dose, and whether there is regulatory precedent. The proposed list is always agreed with you first.
Timelines depend on the scope agreed with you — the number of conditions explored, the techniques required and the depth of characterization. We define the duration together with the study plan, before work begins, and keep you updated as results come in rather than only at the end.
The quantity depends on the type of study and on how many conditions and techniques are involved. We tell you the exact amount when we scope the project, and we design the experimental plan to work with the material you have available.
Yes. Our facility is authorized to handle high-potency active pharmaceutical ingredients up to OEB5, and controlled substances under Ministry of Health authorization, under GMP certification issued by AIFA and following FDA inspection.
A detailed technical-scientific report: experimental conditions, raw analytical data, interpretation and conclusions, written so that it can be used directly in your development documentation and regulatory filings.
Work starts only after a confidentiality agreement is in place. Samples, data and reports remain yours, and results are never shared or reused. We routinely handle undisclosed structures and early-phase candidates.
Send us the free acid or base and your target profile. We will propose a counter-ion set, the material requirement and a timeline before any work begins.