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. 2000 Feb;89(2):268-74.
doi: 10.1002/(SICI)1520-6017(200002)89:2<268::AID-JPS14>3.0.CO;2-F.

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

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Free article

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

J Jinno et al. J Pharm Sci. 2000 Feb.
Free article

Abstract

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

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