The amorphous form is the most soluble and the least stable state your API can take. We develop dispersions that keep the solubility advantage and manage the crystallization risk.
The amorphous form does not possess a defined order in its arrangement. Although it is the most soluble form, it exhibits the lowest stability. Amorphous compounds are produced when precipitation is kinetically faster than crystallisation, and through crystalline disorder caused by processing such as milling or micronisation. More than one distinct amorphous phase may form from the same substance — a behaviour termed amorphous polymorphism.
For poorly water-soluble candidates, this matters commercially. Amorphous materials can significantly increase the bioavailability of drugs that would otherwise fail on exposure, which is why amorphous solid dispersions have become a standard enabling technology rather than a last resort.
The engineering problem is stability. An amorphous solid is thermodynamically driven to crystallize, and when it does, the solubility advantage disappears — sometimes on the shelf, sometimes only after the product reaches the patient. Understanding amorphous crystallization is therefore crucial for process development, and it is where most of the development effort in a dispersion programme is actually spent.
The objective is not simply to make the API amorphous. It is to make an amorphous form that stays amorphous.
Selection of the carrier polymer and drug loading, on the basis of miscibility, glass transition behaviour and the ability to suppress recrystallization.
Spray drying, solvent evaporation, melt and mechanochemical routes, chosen for the thermal and chemical sensitivity of the molecule and for what can later be scaled.
Accelerated and long-term studies under controlled temperature and humidity, monitoring for the first signs of recrystallization rather than waiting for it to be obvious.
Measurement of the supersaturation the dispersion generates and, just as importantly, how long it is maintained before precipitation.
Confirmation of the amorphous state and detection of low levels of crystallinity, using diffraction, thermal analysis and solid-state NMR together.
Assessment of whether the chosen route transfers to larger scale, and what process parameters control the quality of the dispersion.
Dispersion development is an iterative loop between formulation and solid-state analysis, and the analysis is what keeps it honest.
The crystalline API is characterized first — thermal profile, solubility, degradation behaviour — including the glass transition and crystallization tendency of the neat amorphous material.
Candidate polymers and drug loadings are prepared at small scale and assessed for miscibility, single glass transition behaviour and resistance to recrystallization.
The most promising compositions are prepared by the route intended for scale-up, typically spray drying, so that the material tested is representative of the material that would be manufactured.
Each dispersion is confirmed amorphous by diffraction and thermal analysis, with solid-state NMR used where trace crystallinity has to be excluded.
Dissolution testing quantifies the solubility advantage and how long supersaturation is sustained — the property that actually determines exposure.
Dispersions are stored under controlled temperature and humidity and re-analysed on schedule, to establish the crystallization risk over a realistic timescale.
A technical-scientific report covering composition, process, characterization, dissolution behaviour and the stability data behind the recommendation.
Detecting the onset of crystallization at low levels is the analytical heart of this work, and it requires more than one technique.
The study is delivered as a detailed technical-scientific report documenting the composition, the process and the evidence behind the stability assessment.
That is the question the stability programme is designed to answer, and it cannot be answered by prediction alone. We measure it under controlled conditions, report what we observe and state clearly what the data do and do not support.
Yes, and it is one of the reasons we use several techniques rather than diffraction alone. Solid-state NMR and thermal analysis can reveal crystallization well below the level at which an XRPD pattern shows a peak.
No. Spray drying is the most common because it scales predictably, but solvent evaporation, melt methods and mechanochemical routes all have their place, particularly for thermally sensitive molecules. The route is chosen for the molecule, not for convenience.
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.
Tell us the exposure problem you are trying to solve. We will propose a polymer screening and a stability programme sized to the stage you are at.