Rationale for Selection of Dissolution Media: Three Case Studies

Abstract

The selection of media in dissolution method development can sometimes be an arbitrary decision. The case studies in this article give a practical rationale that should help in selecting media, especially surfactants.Three cases were studied: (1) the role of surfactants versus compound stability in the dissolution medium during dissolution method development, (2) the selection of a surfactant based on interactions between the dissolution medium and the drug substance, and (3) the selection of media based on formulation properties.In the first case study, the choice of surfactant in relation to solubility and physical stability of the drug substance is shown. The second revealed an unexpected synergy between polysorbate 20 (Tween) and acetic acid solution that caused an unusual increase in the dissolution rate compared with these media used separately. In the last case study, the medium was modified by addition of surfactant to reflect a change in the formulation.The selection of a dissolution medium should be based on drug substance and formulation characteristics as well as on interactions among components.

Characterization and pharmacokinetic study of itraconazole solid dispersions prepared by solvent-controlled precipitation and spray-dry methods

“…Milled powders of ITZ and F1 to F4 containing 37.5 and 100 mg of ITZ equivalent were poured the acidic phase (0.1 N HCl aqueous solution 750 ml) ( n = 3). After 2 h, 250 ml of 0.2 m trisodium phosphate buffer solution with 2% Tween‐80 (37 °C) was added into the dissolution media to adjust to pH 6.8 . The aliquots were collected at predetermined time points (0.5, 1, 2, 2.15, 2.5, 3, 4, 6, and 8 h).…”

Characterisation of human saliva as a platform for oral dissolution medium development

“…A high interfacial tension reduces wetting of the drug particles and reduces the rate of dissolution. Wetting can be improved by the addition of surfactants, reducing interfacial tension and increasing the rate of dissolution, and it is a common practice to add surfactants to dissolution media [35]. Although many studies have investigated the film forming properties of saliva, as well as salivary pellicle thickness and composition [36], few studies have focussed on the surface tension of whole human saliva [23].…”

Evolution of Choice of Solubility and Dissolution Media After Two Decades of Biopharmaceutical Classification System

“…In predictive dissolution testing, the micelles composed of surfactant molecules mimics the bile acid aggregates in the small intestine; the surfactant facilitates the diffusion and transport of the free solute into the bulk medium. Since dissolution is a combined effect of solubility and diffusivity, the micelle size will have an effect on the dissolution rate of molecules when different surfactants are used (120).…”

“…The 2000 FDA guidance (124) and the 2015 draft guidance (127) measure the solubility of the highest (dose) strength in 250 mL of aqueous medium (67,111,119,120). In contrast, the EMA guidance documents (128), WHO Technical Report (2015) (129), and Health Canada (126) require determining the solubility of the highest single dose administered, which in certain cases can be two or more units in 250 mL (115).…”