Deformulation Analysis

Particle size, shape, and distribution are critical to dissolution and bioavailability, especially in poorly water-soluble drugs (BCS Class II and IV). Determining particle-size distribution in the innovator product supports the development of a bioequivalent formulation. However, the presence of excipients makes standard sizing methods unreliable—microscopy remains the most viable technique.

Deformulation is used for:

• Competitive product analysis
• Generic drug development
• Batch-to-batch variation studies
• Comparative analysis of successful and failed samples
• Legal investigations, including patent or trade secret cases

It also aids in identifying adulterants, verifying label claims, improving quality control, and detecting counterfeit products.

By analyzing the solid-state properties of the API in the RLD, deformulation analysis supports informed decision-making, reduces development risks, and accelerates regulatory timelines. It helps companies achieve bioequivalence efficiently, lowering the chances of bio-failures.

Cost and time advantages are especially valuable for generic drug developers aiming to shorten time-to-market.

Deformulation analysis employs conventional extraction methods alongside instrumental techniques to decode complex mixtures. A significant challenge is differentiating the API from excipients when their particle sizes overlap. Microscopy enables this differentiation through the observation of birefringence patterns and structural characteristics.

A sound reverse engineering strategy involves analyzing particle behavior, identifying the API at both the molecular and particle levels, and evaluating the manufacturing process employed in the original formulation.