Pharmaceutical Deformulation | Reverse Engineering of Drug Formulations
Deformulation is the analytical reconstruction of a finished drug product: which components the formulation contains, in what proportion, and in which solid form. The study delivers qualitative composition, physicochemical properties and characterization of crystallinity, polymorphism and microstructure — the technical evidence needed to develop an equivalent generic.
What is deformulation?
Deformulating means reconstructing, analytically, the composition, solid state and microstructure of a finished drug product. More than a list of results, the study delivers a technical map of the formulation.
The difference between a composition analysis and a deformulation lies in the solid state. Two formulations can share exactly the same declared composition and still behave differently in dissolution, stability and bioavailability, because the active sits in a different polymorph, with different crystallinity, particle size or spatial distribution through the matrix. That layer is what separates a usable development target from a plain ingredient list.
Percevia's approach is risk-oriented: we prioritise high-information assays and avoid redundant steps, cutting cost, turnaround and sample consumption without losing the technical robustness development requires.
From technique to decision
Every technique in the protocol exists to support a specific development decision. None enters the scope without answering a question the client actually needs answered.
| Technique | What it measures | What decision it supports |
|---|---|---|
| XRD · X-Ray Diffraction | Structural organisation of the solid matrix, degree of crystallinity, predominant polymorphic form and presence of an amorphous phase. | Whether your product's solid form matches the reference — and whether it collides with the innovator's solid-state patents. |
| DSC · Differential Scanning Calorimetry | Physical state of the components, thermal events, melting, recrystallisation and glass transition; API–excipient interactions. | Whether amorphisation, recrystallisation or API–excipient incompatibility is compromising physical stability. |
| TGA · Thermogravimetric Analysis | Mass loss, volatile content, hydration and solvation state, thermal stability of the components. | Whether hydrates or solvates explain stability divergences between reference and generic. |
| TERS · Tip-Enhanced Raman Spectroscopy | Localised chemistry at nanometre scale; local heterogeneities, interfaces and microstructural organisation. | How very small API and excipient particles and domains are organised — resolution no bulk technique reaches. |
| Confocal Raman Microscopy | Chemical maps of active distribution through the matrix, spatial homogeneity, API-rich domains and phase segregation. | Whether the spatial distribution of the active — rather than the composition — is the cause of a dissolution deviation. |
| BET · Brunauer–Emmett–Teller | Specific surface area, pore distribution and surface characteristics. | How solid–liquid interaction governs the dissolution kinetics of the tablet. |
| XRF · X-Ray Fluorescence | Salts, mineral excipients, pigments and inorganic compounds. | Which inorganic components complete the compositional reconstruction. |
| Chromatography · HPLC / UPLC / GC-MS | Quantitative basis for each formulation component — API and excipients. | Real content per tablet, anchoring batch-to-batch comparison and the regulatory dossier. |
The four requirements
Every product runs through the same technical sequence, with scope adjusted to formulation complexity and to the client objective.
Qualitative composition
Critical review of the label and public documentation, identification of the declared API and survey of excipients and their technological function. Investigation of non-obvious components — coatings, granulation agents, disintegrants, lubricants, polymers and fillers — and hypotheses about the manufacturing process. Sources: labels, FDA, EMA, ANVISA, Orange Book, patents and pharmacopoeias.
Qualitative composition report
Physicochemical properties
API solubility and pH-dependent solubility profile, pH of the aqueous dispersion, hygroscopicity and moisture content, preliminary stability against hydrolysis and oxidation, mass balance between active fraction and excipient matrix, dispersibility and physical behaviour in aqueous medium.
Interpreted physicochemical data
API quantification
A specific HPLC, UPLC or LC-MS method with selectivity against the excipients, including sample preparation, calibration curve and validation to the applicable regulatory requirements. It can be omitted at the initial stage when the dose is already declared on the label, and added when regulatory need or batch comparison calls for it.
Real content per tablet, with a validated method
Solid state and microstructure
The technical core of the study: spatial distribution of the API, particle size, crystallinity and polymorphism, thermal properties, morphology and porosity. These are the attributes that directly drive dissolution, stability, processability and bioavailability.
Advanced solid-state characterization, with chemical maps
Applications
The same technical map supports four distinct development fronts.
Development
Generics and similars
Reconstructs the architecture of the reference formulation and sets a clear technical target for developing an equivalent product.
Optimisation
Formulation troubleshooting
Explains dissolution, stability or processability failures and points to the solid-state or compositional variable behind them.
Regulatory
Dossier and equivalence
Generates composition, solid-state and microstructure evidence to support comparability and pharmaceutical equivalence studies.
Risk & IP
Solid state and patents
Anticipates polymorphism and crystallinity risk and positions the solid form against the innovator's solid-state patents.
What you receive
A consolidated, interpreted technical package — not a set of loose test reports.
Data and evidence
- Processed experimental data and results interpreted per analytical technique
- Relevant images, spectra, diffractograms and thermograms
- Critical assessment of the qualitative composition of the product
- Discussion of the API solid state and the spatial distribution of the active
Interpretation and conclusions
- Interpretation of the tablet microstructure
- Discussion of risks tied to crystallinity, polymorphism, particle size, porosity and API distribution
- Integrated technical conclusions
- Recommendations for the subsequent development stages
Turnaround and scope
Scope is risk-oriented: we prioritise the assays that most reduce development uncertainty and drop those that would not change the decision.
- High-information assays first, avoiding redundant steps
- Absolute API quantification omitted when the dose is already known and not essential to the decision
- Focus on qualitative composition, solid state, microstructure and active distribution
- Lower cost, turnaround and sample consumption, keeping the robustness development requires
- Suited to portfolios with high unit cost and limited sample availability
Frequently asked questions
What is deformulation of a drug product?
- Deformulation is the analytical reconstruction of a finished drug product: identifying which components the formulation contains, in what proportion, and which solid form the active sits in. The result is a technical map of the formulation, built from experimental evidence rather than from a label or the literature.
What is the difference between reverse engineering and deformulation?
- In analytical practice the terms are used interchangeably. Reverse engineering is the broader term, applied to any product; deformulation is the term used when the object is a chemical formulation — a drug, a cosmetic, a personal care product.
Is deformulation legal?
- Analysing a product lawfully acquired on the open market is legal. What the analysis does not authorise is infringing live patents, using improperly obtained trade secrets or breaching contractual agreements. Analytical evidence of composition and solid state is in fact often used to verify freedom to operate before investing in development.
How long does a deformulation study take?
- Typical turnaround is 30 days for the essential scope. Studies including validated absolute quantification, or highly complex formulations, can extend that, which is agreed before work begins.
What is the minimum sample quantity required?
- It depends on scope, but the risk-oriented approach was designed precisely for portfolios with scarce samples and high unit cost. Omitting extensive quantitative assays at the initial stage cuts material consumption substantially. The exact quantity is set in the proposal, once we understand the objective of the study.
Does the API have to be quantified?
- Not at the initial stage. When the dose is already declared on the label and the goal is to understand the architecture of the formulation, absolute quantification can be omitted without weakening the development decision. It is added when there is a regulatory need, a batch comparison or a content uniformity check.
What does solid-state characterization add over composition alone?
- Composition answers what is in the formulation. Solid state answers why it behaves the way it does. Crystallinity, polymorphism, amorphous fraction, particle size and spatial distribution of the active govern dissolution, stability and bioavailability. Without that layer you can reproduce the ingredient list and still fail equivalence.
Does deformulation identify polymorphism and patent risk?
- Yes. XRD and DSC establish the predominant polymorphic form, the degree of crystallinity and the presence of an amorphous phase. That allows the solid form of your product to be compared against the one claimed in the innovator's solid-state patents, and the risk anticipated before bench investment.
Do the results support equivalence evidence for ANVISA?
- The study generates composition, solid-state and microstructure evidence that supports comparability and underpins pharmaceutical equivalence studies. It does not replace the equivalence or bioequivalence testing required by regulation, but it provides the technical basis to run those with a defined target and lower risk of failure.
Can the reference formulation be replicated exactly?
- No analytical study delivers the manufacturing recipe. Deformulation reconstructs composition, solid state and microstructure, and infers the likely architecture and clues about the process. Process parameters — order of addition, granulation conditions, compression force — are inferred, not measured. The result is a technical target, not a copy.
Is the information handled confidentially?
- Yes. Scope, samples, results and the very existence of the study are treated as client confidential information, under a confidentiality agreement signed before samples are sent.
Which product types can be deformulated?
- Tablets and solid oral dosage forms are the focus of this approach. The same methodology applies to topical forms, cosmetic and personal care formulations, and modified-release products, with the protocol adjusted to the complexity of the matrix.
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Scope is risk-oriented: we prioritise the assays that most reduce development uncertainty and drop those that would not change the decision.
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