Solid Form Screening and Selection Optimizing Quality and Performance from Discovery to NDA

Optimizing Quality and Performance from Discovery to NDA

Small molecule APIs can exist in multiple solid forms, including polymorphs, hydrates, solvates, salts, co-crystals, and amorphous states. The selected solid form directly impacts solubility, stability, bioavailability, and manufacturability. Comprehensive solid form screening and selection are therefore critical to ensuring product quality, clinical performance, and scalable manufacturing.

As a specialized CRO/CDMO in solid-state research, Crystal Pharmatech provides integrated capabilities in physicochemical characterization and solid form selection, including XRPD, TGA, DSC, PLM, and particle size analysis. Advanced workflows support polymorph screening, salt and co-crystal selection, and single-crystal structure determination.

Facilities are equipped to handle highly potent compounds (OEB 4 and 5) as well as controlled substances, ensuring safe and compliant execution across development programs

Phase-Appropriate Solid Form Screening Strategies

Screening strategies are designed to align with the evolving needs of each stage of drug development, from early discovery to late-stage clinical development.

Targeted manual screening for early-stage evaluation:

Rapid assessment of key physicochemical properties and initial form identification during drug discovery (focused form screening).

Integrated virtual and experimental screening approaches:

Use of predictive modeling (e.g., quantum chemistry and COSMO-RS thermodynamics) combined with automated workflows to evaluate phase behavior, stability, and form selection (preclinical to IND).

High-throughput screening for comprehensive form space evaluation:

High-throughput screening for comprehensive form space evaluation

Core Solid Form Screening Services

01. Polymorph Screening and Selection

Polymorph screening is prioritized when solid form variability may impact development outcomes. The objective is to map the polymorphic landscape of an API and identify the most thermodynamically stable form with optimal stability, hygroscopicity, and melting behavior.

Screening Workflow

Crystallization condition design based on API physicochemical properties
Comprehensive identification and characterization of all solid forms
Thermodynamic phase relationship analysis, including stability and solubility evaluation
Data-driven selection of the optimal polymorph for downstream development

Late-Stage IP Screening

At late-stage clinical development, solid form screening supports intellectual property strategy. Extensive screening is conducted to identify all relevant forms — including metastable forms — to ensure robust patent protection and industrial applicability.

02. Salt Screening and Selection

Salt screening is applied when improvements in solubility, stability, or bioavailability are required. Systematic evaluation of salt forms enables identification of optimal candidates for scalable development.

Screening Workflow

Salt selection and experimental design tailored to API ionization properties
Generation and characterization of salt forms
Thermodynamic and stability evaluation, including solubility profiling
Strategic salt selection based on developability and manufacturability criteria

03. Co-Crystal Screening and Selection

For non-ionizable or weakly ionizable compounds, co-crystallization provides an alternative strategy to modify physicochemical properties. Co-crystal screening leverages API–co-former interactions to improve solubility, stability, and solid-state behavior.

Screening Workflow

Selection of suitable co-formers to guide experimental design
Synthesis and structural characterization of co-crystal forms
Evaluation of phase behavior, stability, and solubility
Identification of optimal co-crystal candidates for development

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Our capabilities span three specialized platforms:

Small Molecule
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