Tailoring Co-crystal Solubility via Solution Phase Chemistry

3 Tailoring Co-crystal Solubility via Solution Phase Chemistry 

Consider a 1 1 co-crystal RHA where R is a non-ionizable drug and HA is a monoprotic acidic co-former. If the co-crystal-solution equihbria are described by co-crystal dissociation and co-former ionization, the equihbrium expressions and associated constants are  

The total co-former analytical concentration is the sum of the ionized and non-ionized species, which for a weak acid is given by  

Drug concentration in equilibrium with co-crystal can be expressed in terms of co-former equilibrium concentration, [A]t, ionization constant, co-crystal sp, and solution [H ] by substituting [HA] and [A ] from equations (11.9), (11.10), and (11.11) into equation (11.12) and rearranging to give  

Total drug concentration at equilibrium, [Rj-p, is shown as the dependent variable, since it is generally of interest to know how co-crystal solubility varies with co-former concentration and pH. Under these conditions  

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