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Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid) in Simulated Intestinal Fluids.

Knöös P, Svensson AV, Ulvenlund S, Wahlgren M - PLoS ONE (2015)

Bottom Line: Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery.Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media.However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Division of Physical Chemistry, Lund University, Lund, Sweden.

ABSTRACT
A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium) or fed state (FeSSIF). The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated.

No MeSH data available.


Release of griseofulvin from tablet without SDS (Formulation 1) in buffer (open circles), FaSSIF (open square) and FeSSIF (filled square).Error bars represent standard deviation (n = 2).
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pone.0140709.g006: Release of griseofulvin from tablet without SDS (Formulation 1) in buffer (open circles), FaSSIF (open square) and FeSSIF (filled square).Error bars represent standard deviation (n = 2).

Mentions: The release of griseofulvin from Pemulen TR2 tablets without added surfactant (Formulation 1) is shown in Fig 6 for tablets dissolving in buffer and SIF solutions. The tablets generally showed a slow and linear release rate, which is retained throughout the experimental period. None of the tablets were dissolved after eight days. Tablets dissolving in SIF media showed an even slower release than in buffer and clear differences can be established between the tablets in the various media. The slowest release was in FeSSIF solution. The tablets in SIF were not fully dissolved during the experimental period. However, after four days the SIF solutions became more and more turbid, and at after even longer dissolution the solutions turned milky. Hence, the solutions were not considered stable throughout the extended experimental time and the experiments were ended before complete dissolution.


Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid) in Simulated Intestinal Fluids.

Knöös P, Svensson AV, Ulvenlund S, Wahlgren M - PLoS ONE (2015)

Release of griseofulvin from tablet without SDS (Formulation 1) in buffer (open circles), FaSSIF (open square) and FeSSIF (filled square).Error bars represent standard deviation (n = 2).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608824&req=5

pone.0140709.g006: Release of griseofulvin from tablet without SDS (Formulation 1) in buffer (open circles), FaSSIF (open square) and FeSSIF (filled square).Error bars represent standard deviation (n = 2).
Mentions: The release of griseofulvin from Pemulen TR2 tablets without added surfactant (Formulation 1) is shown in Fig 6 for tablets dissolving in buffer and SIF solutions. The tablets generally showed a slow and linear release rate, which is retained throughout the experimental period. None of the tablets were dissolved after eight days. Tablets dissolving in SIF media showed an even slower release than in buffer and clear differences can be established between the tablets in the various media. The slowest release was in FeSSIF solution. The tablets in SIF were not fully dissolved during the experimental period. However, after four days the SIF solutions became more and more turbid, and at after even longer dissolution the solutions turned milky. Hence, the solutions were not considered stable throughout the extended experimental time and the experiments were ended before complete dissolution.

Bottom Line: Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery.Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media.However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Division of Physical Chemistry, Lund University, Lund, Sweden.

ABSTRACT
A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium) or fed state (FeSSIF). The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated.

No MeSH data available.