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In vivo dissolution of poorly water-soluble drugs: Proof of concept based on fluorescence bioimaging.

ABSTRACT: In vitro‒in vivo correlation (IVIVC) of solid dosage forms should be established basically between in vitro and in vivo dissolution of active pharmaceutical ingredients. Nevertheless, in vivo dissolution profiles have never been accurately portrayed. The current practice of IVIVC has to resort to in vivo absorption fractions (F _a). In this proof-of-concept study, in vivo dissolution of a model poorly water-soluble drug fenofibrate (FNB) was investigated by fluorescence bioimaging. FNB crystals were first labeled by near-infrared fluorophores with aggregation-caused quenching properties. The dyes illuminated FNB crystals but quenched immediately and absolutely once been released into aqueous media, enabling accurate monitoring of residual drug crystals. The linearity established between fluorescence and crystal concentration justified reliable quantification of FNB crystals. In vitro dissolution was first measured following pharmacopoeia monograph protocols with well-documented IVIVC. The synchronicity between fluorescence and in vitro dissolution of FNB supported using fluorescence as a measure for determination of dissolution. In vitro dissolution correlated well with in vivo dissolution, acquired by either live or ex vivo imaging. The newly established IVIVC was further validated by correlating both in vitro and in vivo dissolution with F _a obtained from pharmacokinetic data.

SUBMITTER: Yang Y

PROVIDER: S-EPMC8105772 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Multicomponent cyclodextrin system for improvement of solubility and dissolution rate of poorly water soluble drug.

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| S-EPMC4896148 | biostudies-literature

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| S-EPMC4113620 | biostudies-other

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Controlled Suspensions Enable Rapid Determinations of Intrinsic Dissolution Rate and Apparent Solubility of Poorly Water-Soluble Compounds.

Project description:To develop a small-scale set-up to rapidly and accurately determine the intrinsic dissolution rate (IDR) and apparent solubility of poorly water-soluble compounds.The IDR and apparent solubility (Sapp) were measured in fasted state simulated intestinal fluid (FaSSIF) for six model compounds using wet-milled controlled suspensions (1.0% (w/w) PVP and 0.2% (w/w) SDS) and the μDISS Profiler. Particle size distribution was measured using a Zetasizer and the total surface area was calculated making use of the density of the compound. Powder and disc dissolution were performed and compared to the IDR of the controlled suspensions.The IDR values obtained from the controlled suspensions were in excellent agreement with IDR from disc measurements. The method used low amount of compound (μg-scale) and the experiments were completed within a few minutes. The IDR values ranged from 0.2-70.6 μg/min/cm2 and the IDR/Sapp ratio ranged from 0.015 to 0.23. This ratio was used to indicate particle size sensitivity on intestinal concentrations reached for poorly water-soluble compounds.The established method is a new, desirable tool that provides the means for rapid and highly accurate measurements of the IDR and apparent solubility in biorelevant dissolution media. The IDR/Sapp is proposed as a measure of particle size sensitivity when significant solubilization may occur.

| S-EPMC5533823 | biostudies-other

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Project description:This paper addresses the problem of ocular delivery of lipophilic drugs. The aim of the paper is the evaluation of polymeric micelles, prepared using TPGS (d-?-Tocopheryl polyethylene glycol 1000 succinate), a water-soluble derivative of Vitamin E and/or poloxamer 407, as a vehicle for the ocular delivery of dexamethasone, cyclosporine, and econazole nitrate. The research steps were: (1) characterize polymeric micelles by dynamic light scattering (DLS) and X-ray scattering; (2) evaluate the solubility increase of the three drugs; (3) measure the in vitro transport and conjunctiva retention, in comparison to conventional vehicles; (4) investigate the mechanisms of enhancement, by studying drug release from the micelles and transconjunctival permeation of TPGS; and (5) study the effect of micelles application on the histology of conjunctiva. The data obtained demonstrate the application potential of polymeric micelles in ocular delivery, due to their ability to increase the solubility of lipophilic drugs and enhance transport in and across the conjunctival epithelium. The best-performing formulation was the one made of TPGS alone (micelles size ? 12 nm), probably because of the higher mobility of these micelles, an enhanced interaction with the conjunctival epithelium, and, possibly, the penetration of intact micelles.

| S-EPMC6781556 | biostudies-literature

Release kinetics study of poorly water-soluble drugs from nanoparticles: are we doing it right?

Project description:In vitro drug release kinetics studies are routinely performed to examine the ability of new drug formulations to modulate drug release. The underlying assumption is that the studies are performed in a sufficiently dilute solution, where the drug release is not limited by the solubility and the difference in release kinetics profile reflects the performance of a drug carrier in vivo. This condition is, however, difficult to meet with poorly water-soluble drug formulations, as it requires a very large volume of release medium relative to the formulation mass, which makes it challenging to measure the drug concentration accurately. These difficulties are aggravated with nanoparticle (NP) formulations, which are hard to separate from the release medium and thus require a dialysis bag or repeated high-speed centrifugation for sampling. Perhaps for these reasons, drug release kinetics studies of NPs of poorly water-soluble drugs are often performed in suboptimal conditions in which the NPs are not sufficiently diluted. However, such a practice can potentially underestimate drug release from NPs, leading to an inaccurate prediction that the NPs will attenuate the drug activity in vivo. Here we perform release kinetics studies of two different NP formulations of paclitaxel, a representative poorly water-soluble drug, according to common practices in the literature. We find that the drug release from NPs can be substantially underestimated depending on the choice of the release medium, NP/medium ratio, and handling of release samples. We discuss potential consequences of underestimating drug release, ending with suggestions for future studies with NP formulations of poorly water-soluble drugs.

| S-EPMC4764376 | biostudies-literature

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