Dissolution of slightly Soluble Drugs. V. Effect of Particle Size on Gastrointestinal Drug Absorption and Its Relation to Solubility

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Experiments were made on the effect of particle size on gastrointestinal drug absorption in the rabbit and its relation to solubility using powder drugs, in a series of solubility ranging from 1 to 25 mg/ml at 37°in suspension, and a consideration was made on the relationship between solubility and bioavailability on the basis of particle size, with following results. 1) The blood concentration-time curves at the particle size up to some sizes showed a similar time course curve obtained with an aqueous solution of each drug. Provided that the maximum particle size limit which described a time course curve similar to that of solution was the critical particle size (CPS), effect of particle size on the blood level appeared above the CPS of a drug. The CPS depended mainly on the solubility with slight relation of individual absorption rate of each drug solution and increased linearly with an increase in solubility. The extent of availability for different particle size grades was almost constant in each powder drug. 2) General consideration was made on the relationship between solubility and bioavailability on the basis of a particle size. This relation may vary with other factors, especially, dosage forms such as tablet, capsule, etc., physiological factors, and individual properties of the drugs. However, this relation would be useful as a temporary standard as for considering the relationship between solubility and bioavailability on the basis of particle size.
公益社団法人日本薬学会の論文
1978-09-25

Dissolution of slightly Soluble Drugs. V. Effect of Particle Size on Gastrointestinal Drug Absorption and Its Relation to Solubility

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