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Supersaturating drug delivery systems are used to achieve higher oral bioavailability for poorly soluble drugs. However, supersaturated solutions often decline to lower concentrations by precipitation and crystallization. The purpose of the current research is to provide a mechanistic understanding of drug crystallization as a function of pH, using indomethacin (IMC, pK a 4.18) as a model compound. Desupersaturation kinetics to the γ-form of IMC was measured at pH 2.0, 3.0, 4.0, and 4.5 from an initial degree of supersaturation of 2.5−6. At equivalent levels of supersaturation, crystal growth rates decreased with an increase in solution pH. Two mechanisms for this phenomenon, reactive diffusion (resulting in a higher surface pH as compared to bulk pH) and inhibition of crystallization by structurally similar ionized IMC at higher pH, were explored. Non-steady-state models for reactive diffusion showed that the surface pH was only 0.01 units above that of the bulk solution pH. Mass transport models for reactive diffusion during crystallization could not explain the decrease in desupersaturation kinetics at higher pH. However, zeta potentials as high as −70 mV suggested that IMC − is adsorbed on the surface of the particles. A mathematical model for inhibition of crystal growth by IMC − accounted for the pH effect suggesting that ionized IMC acts as an effective crystallization inhibitor of IMC.

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The rheological behaviour of cellulose fermentation broths of Penicillium funiculosum culture has been investigated. The shear stress‐shear rate behaviour is explained satisfactorily by a power law model, although there appear to be small yield stresses, particularly at high substrate concentrations.