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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 tablets containing SDS (Formulation 2) in buffer buffer (open circles), FaSSIF (open square) and FeSSIF (filled square).Error bars represent standard deviation (n = 2).
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pone.0140709.g007: Release of griseofulvin from tablets containing SDS (Formulation 2) in buffer buffer (open circles), FaSSIF (open square) and FeSSIF (filled square).Error bars represent standard deviation (n = 2).

Mentions: Tablets containing SDS (Formulation 2) behaved differently in many key aspects, see Fig 7. Most importantly, the differences in release profile between the different media were lost and the tablets of Formulation 2 showed similar release rates and profiles in all media. Examining the tablets visually in the bath during dissolution showed that all tablets formed thick gel layers and only small amounts of eroded tablet particles could be seen in the baths. None of the tablets were dissolved completely during the experimental time. However, due to the physical instability of the SIF solutions (see above) the experiments were terminated after eight days. Due to there composition SIF and FASSIF is not fully stable for eight days but the experiments were followed as long as possible to see if any changes from the zero order profile could be observed.


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 tablets containing SDS (Formulation 2) in buffer 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.g007: Release of griseofulvin from tablets containing SDS (Formulation 2) in buffer buffer (open circles), FaSSIF (open square) and FeSSIF (filled square).Error bars represent standard deviation (n = 2).
Mentions: Tablets containing SDS (Formulation 2) behaved differently in many key aspects, see Fig 7. Most importantly, the differences in release profile between the different media were lost and the tablets of Formulation 2 showed similar release rates and profiles in all media. Examining the tablets visually in the bath during dissolution showed that all tablets formed thick gel layers and only small amounts of eroded tablet particles could be seen in the baths. None of the tablets were dissolved completely during the experimental time. However, due to the physical instability of the SIF solutions (see above) the experiments were terminated after eight days. Due to there composition SIF and FASSIF is not fully stable for eight days but the experiments were followed as long as possible to see if any changes from the zero order profile could be observed.

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.