Polymorphs, Salts, and Cocrystals: What’s in a Name?

TLDR

The 2011 FDA draft guidance on pharmaceutical cocrystals addressed a proposed definition and classification of cocrystals as API‑excipient complexes. This perspective summarizes the Indo–U.S. Bilateral Meeting discussion and incorporates input from non‑participants. The meeting included a dedicated session on the FDA guidance draft and drew contributions from researchers beyond the attendees. Participants reached consensus that cocrystals should be defined more broadly and classified like salts, yet the diverse API crystal forms complicate a mutually exclusive three‑category classification.

Abstract

The December 2011 release of a draft United States Food and Drug Administration (FDA) guidance concerning regulatory classification of pharmaceutical cocrystals of active pharmaceutical ingredients (APIs) addressed two matters of topical interest to the crystal engineering and pharmaceutical science communities: (1) a proposed definition of cocrystals; (2) a proposed classification of pharmaceutical cocrystals as dissociable "API-excipient" molecular complexes. The Indo–U.S. Bilateral Meeting sponsored by the Indo–U.S. Science and Technology Forum titled The Evolving Role of Solid State Chemistry in Pharmaceutical Science was held in Manesar near Delhi, India, from February 2–4, 2012. A session of the meeting was devoted to discussion of the FDA guidance draft. The debate generated strong consensus on the need to define cocrystals more broadly and to classify them like salts. It was also concluded that the diversity of API crystal forms makes it difficult to classify solid forms into three categories that are mutually exclusive. This perspective summarizes the discussion in the Indo–U.S. Bilateral Meeting and includes contributions from researchers who were not participants in the meeting.