CHARACTERIZATION OF ADSORPTION BEHAVIOR BY SOLID DOSAGE FORM EXCIPIENTS IN FORMULATION DEVELOPMENT

The adsorption of drugs onto solid dosage form excipients may influence dissolution characteristics, analytical testing and bioavailability. CI-977 ([5R-(5-alpha,7-alpha,8-beta)]-N-methyl-N-[7-(pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-4-benzofuranacetamide monohydrochloride), a kappa-opioid agonist analgesic compound, was found to adsorb onto microcrystalline cellulose, croscarmellose and sodium starch glycolate. The extent of adsorption was affected by pH, ionic strength and ionic species. The adsorptive capacity and relative affinity for CI-977 adsorption to microcrystalline cellulose was characterized under various experimental conditions using Langmuir isotherms. The results show that electrolytes inhibit adsorption by reducing both the affinity of the adsorbent for the adsorbate and the adsorptive capacity of the adsorbent. Divalent cations reduced the adsorption to a greater extent than monovalent cations. The effects of pH and electrolytes suggest that the predominant mechanism of CI-977 adsorption to microcrystalline cellulose is electrostatic attractive forces.