Abstract
Crystal form can be crucial to the performance of a dosage form. This is especially true for compounds that have intrinsic barriers to drug delivery, such as low aqueous solubility, slow dissolution in gastrointestinal media, low permeability and first-pass metabolism. The nature of the physical form and formulation tends to exhibit the greatest effect on bioavailability parameters of water insoluble compounds that need to be given orally in high doses. An alternative approach available for the enhancement of drug solubility, dissolution and bioavailability is through the application of crystal engineering of co-crystals. The physicochemical properties of the active pharmaceutical ingredients and the bulk material properties can be modified, whilst maintaining the intrinsic activity of the drug molecule. This article covers the advantages of co-crystals over salts, solvates (hydrates), solid dispersions and polymorphs, mechanism of formation of co-crystals, methods of preparation of co-crystals and application of co-crystals to modify physicochemical characteristics of active pharmaceutical ingredients along with the case studies. The intellectual property implications of creating co-crystals are also highly relevant.
Highlights
Crystal form can be crucial to the performance of a dosage form
The pharmaceutical industry’s mission is to rapidly advance development programs with good confidence so that formulation problems are unlikely to arise and to maximize a compounds potential as a therapeutic. This commentary seeks to raise the profile of crystal form studies and the emerging topic of crystal engineering in pharmaceutical science by discussing the state-of-the-art relating to pharmaceutical crystals and by expanding on possibilities that exist for future developments
The stable crystal form of the parent compound may exhibit inadequate solubility or dissolution rate resulting in poor oral absorption, for water-insoluble compounds
Summary
- August 2009 www.ijpsonline.com the nature of the molecule of interest and type of physical property challenges faced in its development. The key benefits associated with co-crystallization approach to modify properties of pharmaceutical solids are the theoretical capability of all types of drug molecules, including weakly ionizable and nonionizable, to form co-crystals, and the existence of numerous, potential counter-molecules, including food additives, preservatives, pharmaceutical excipients as well as other APIs, for co-crystal synthesis. Co-crystals having advantages like stable crystalline form (as compared to amorphous solids), no need to make or break covalent bonds, theoretical capability of all types of API molecules (weakly ionizable/ non-ionizable) to form co-crystals, the existence of numerous potential counter-molecules (food additives, preservatives, pharmaceutical excipients, and other APIs), the only solid form that is designable via crystal engineering patentable expanding IP portfolios and can be produced using solid-state synthesis green technologies high yield, no solvent or by-products. The weak hydrogen bonds involves the –C-H---O and C-H---O=C[15]
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