Drug membrane transport enhancement using high energy drug polyvinylpyrrolidone (PVP) co-precipitates

Abstract

Dissolution rate data obtained with sulfathiazoie-povidone(PVP) co-precipitates and hydrocortisone-povidone co-precipitates were compared to cellophane membrane diffusion data obtained with the co-precipitates. The hypothesis, that the rate-limiting drug phases in the co-precipitate dissolution experiments were high energy amorphous phases of the drug, was tested. In regions of the dissolution rate studies where the carrier effects due to the PVP-drug complexes were small, the dissolution rates for the two PVP-drug systems agreed well with the results of the membr~e diffusion experiments. The normalized fluxes were found to be about 3.5 for the high energy phase of sulfathiazole and 14-18 for that of hydrocortisone.

Dissolution and Precipitation Behavior of Amorphous Solid Dispersions

“…This indicates that, at least over the timeframe that these experiments were conducted, there is no significant difference in the maximum thermodynamic activity of dissolved felodipine for solutions derived from the three amorphous systems. Additionally, this technique confirms that felodipine was not complexed with HPMC in the bulk solution as has been demonstrated in other systems under similar conditions 26,27. On the basis of the measured concentrations from the UV probe experiments (Fig.…”

Initial Drug Dissolution from Amorphous Solid Dispersions Controlled by Polymer Dissolution and Drug-Polymer Interaction

“…Amorphous solid dispersion (ASD), wherein drug molecules disperse within a polymer matrix usually at a drug loading above its crystalline solubility in polymer, is a thermodynamically metastable binary composite that serves as an indispensable formulation technology to improve solubility and bioavailability of increasing number of poorly water soluble drugs (1)(2)(3)(4)(5)(6)(7)(8)(9). Immediately upon contact with aqueous medium, amorphous drug usually dissolves much more rapidly compared with crystalline dose forms, due to the absence of crystal lattice, and the existence of water-soluble polymers.…”

Impact of Solubilizing Additives on Supersaturation and Membrane Transport of Drugs

“…Felodipine and nifedipine were used as model drug substances and a variety of solubilizing additives including surfactants were evaluated. Diffusion rates across a membrane were studied using a sideby-side diffusion cell as described previously (8,27). The impact of the additives on equilibrium solubility was determined and linked to the changes in the flux values of solutions containing different concentrations of the drug and additives.…”