Maintenance of Supersaturation II: Indomethacin Crystal Growth Kinetics Versus Degree of Supersaturation

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

“…This could be attributed to the greater affinity and greater extent of adsorption of higher molecular weight PVP for indomethacin crystals. The values of k G of indomethacin at a high degree of supersaturation ( S ∼5) in the presence of PVP K12, K16–18, and K29–32 (i.e., 1.0 ± 0.2 × 10 −4 , 1.1 ± 0.6 × 10 −4 , and 3.0 ± 1.9 × 10 −5 cm/s, respectively) were somewhat reduced in comparison with the k G of the surface integration controlled crystal growth of indomethacin as determined in a previous study at low S in the absence of PPIs (i.e., 5.5 ± 1.3 × 10 −4 cm/s) . The k G of the bulk diffusion controlled crystal growth of indomethacin at high S in the absence of PVP is 4.7 ± 0.7 × 10 −3 cm/s .…”

“…The k G of the bulk diffusion controlled crystal growth of indomethacin at high S in the absence of PVP is 4.7 ± 0.7 × 10 −3 cm/s . This suggested that the adsorbed PVP changed the mechanism of indomethacin crystal growth at high S such that the rate limiting step changed from bulk diffusion to surface integration . The change in crystal growth mechanism could be attributed to the inhibition of the formation of a high energy surface layer on indomethacin crystals by the adsorbed PVP as indicated by the similarity between the apparent solubility of indomethacin after crystal growth in the presence of PVP and the equilibrium solubility of the γ‐form of indomethacin in the presence of PVP but without any crystal growth .…”

“…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.…”

Evolution of Supersaturation of Amorphous Pharmaceuticals: Nonlinear Rate of Supersaturation Generation Regulated by Matrix Diffusion

“…This is consistent with our previous findings 11 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 22 Supersaturation provides the driving force for crystal nucleation and growth and the kinetics of the overall crystallization process depends on the degree of supersaturation [30][31][32][33] . The relationship between indomethacin crystallization kinetics and the degree of supersaturation has been previously investigated 27 . The degree of supersaturation generated by supersaturating drug delivery systems in in vitro studies also depends on the drug loading, matrix composition and preparation method 34 .…”

Biopharmaceutic Profiling of Salts to Improve Absorption of Poorly Soluble Basic Drugs

“…There are some reports available regarding formulation strategies that can be applied to inhibit in vivo precipitation. [29][30][31][32][33] The cannabinoid receptor 1 antagonists AZD1175 and AZD2207 are highly lipophilic weak bases with low pH-dependent solubility and high intestinal permeability in the Caco-2 model ( Fig. 1 and Table 1).…”