Maintenance of Supersaturation I: Indomethacin Crystal Growth Kinetic Modeling Using an Online Second-derivative Ultraviolet Spectroscopic Method

Adsorption of Polyvinylpyrrolidone and its Impact on Maintenance of Aqueous Supersaturation of Indomethacin via Crystal Growth Inhibition

“…PXRD patterns also showed no significant change upon crystal growth. Additional discussions on the seed crystal characterization before and after crystal growth in the absence of PPIs are provided in an earlier publication …”

“…The adsorption of nitrogen onto indomethacin crystals was measured using a Tristar 3000 automated adsorption apparatus (Micromeritics, Norcross, Georgia, USA). Indomethacin seed crystals, before and after growth, were characterized for crystal form, size, number, and morphology using previously described methods . Briefly, the PXRD patterns of indomethacin crystals before and after crystal growth were obtained using an X‐ray diffractometer (Bruker D8 Advance; Bruker AXS, Inc., Madison, Wisconsin) to determine any possible change in the form of indomethacin from the most stable γ‐form to either an amorphous form or another metastable form such as the α‐form.…”

“…The supersaturated suspensions were magnetically stirred at about 400 rpm using a pivoted rod‐shaped magnetic stir bar. The change in concentration of indomethacin from its supersaturated suspensions was measured using a second derivative online UV spectroscopy method . The second derivative of the UV absorbance at 295 nm, obtained from an indomethacin UV absorbance spectrum from 210 to 400 nm wavelength, was used to determine indomethacin concentration.…”

“…Although some PPIs including surfactants such as TPGS and polysorbate 80 could increase the equilibrium solubility of drugs, the precipitation inhibitory effects of PPIs are generally kinetic in nature. The PPIs maintain supersaturation through the inhibition of either nucleation, crystal growth or both . The inhibitory effects of PPIs on nucleation, crystal growth, or both vary significantly with the specific drug and PPI combination.…”

Supersaturable solid self-microemulsifying drug delivery system: precipitation inhibition and bioavailability enhancement

“…The higher the initial degree of supersaturation, the more rapid precipitation will happen. 34 Recently, a series of pharmaceutical excipients have been successfully explored as precipitation inhibitors ("parachutes") for temporary inhibition of drug precipitation. 35 Inhibition of drug precipitation can be achieved thermodynamically by reducing the degree of supersaturation, or kinetically by inhibiting or retarding the drug precipitation in supersaturated systems.…”