Dissolution of ionizable water-insoluble drugs: the combined effect of pH and surfactant.

摘要: This study reports the results of combined effect pH and surfactant on dissolution piroxicam (PX), an ionizable water-insoluble drug in physiological pH. The intrinsic rate (J(total)) PX was measured range from 4.0 to 7.8 with 0%, 0.5%, 2.0% sodium lauryl sulfate (SLS) using rotating disk apparatus. Solubility (c(total)) also same SLS concentration ranges. A simple additive model including ionization (PX H(+) + PX(-)) two micellar solubilization equilibria micelle [PX](micelle), PX(-) [PX(-)](micelle)) were considered convective diffusion reaction model. J(total) c(total) increased increasing approximately manner. Nonlinear regression analysis showed that observed experimental data well described proposed (r(2) = 0.86, P < 0.001 for r(2) 0.98, c(total)). pK(a) value 5.63 +/- 0.02 estimated agreed reported value. equilibrium coefficient unionized be 348 77 L/mol, while ionized nearly equal zero. coefficients species PX, PX(-), [PX](micelle) as (0. 93 0.35) x 10(-5), (1.4 0.30) (0.59 0.21) 10(-5) cm(2)/s, respectively. total flux enhancement is less than solubility due smaller species. may useful predicting water insoluble a function establishing vitro-in vivo correlations, IVIVC, maintaining bioequivalence products.