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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.


The elastic (G’, black bars) and viscous (G”, hatched bars) moduli at 0.2 Hz shown for 1 wt% model gels in dissolution media with (+SDS) and without SDS in the gels.The SDS concentration was ca. 8 mM. The data points represent the mean values of two measurements and error bars show the standard deviation (n = 2).
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pone.0140709.g005: The elastic (G’, black bars) and viscous (G”, hatched bars) moduli at 0.2 Hz shown for 1 wt% model gels in dissolution media with (+SDS) and without SDS in the gels.The SDS concentration was ca. 8 mM. The data points represent the mean values of two measurements and error bars show the standard deviation (n = 2).

Mentions: All gels formed in the dissolution media were highly viscous and did not flow visibly when tilted. Clear gels were formed in buffered solution and FaSSIF, whereas gels in FeSSIF were slightly turbid. This agrees with the results and discussion above and it can be hypothesized that NaTC and lecithin formed large mixed aggregates in the gel, which scatter light. Interestingly, if SDS was added to the gels (in a similar ratio as in the tablets, see below) the turbidity of the FeSSIF gels decreased, probably due to solubilisation of lecithin. As can be seen the rheology of FaSSIF and FeSSIF gels differed significantly but when SDS is added this variation is considerably decreased, Fig 5.


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)

The elastic (G’, black bars) and viscous (G”, hatched bars) moduli at 0.2 Hz shown for 1 wt% model gels in dissolution media with (+SDS) and without SDS in the gels.The SDS concentration was ca. 8 mM. The data points represent the mean values of two measurements and error bars show the standard deviation (n = 2).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140709.g005: The elastic (G’, black bars) and viscous (G”, hatched bars) moduli at 0.2 Hz shown for 1 wt% model gels in dissolution media with (+SDS) and without SDS in the gels.The SDS concentration was ca. 8 mM. The data points represent the mean values of two measurements and error bars show the standard deviation (n = 2).
Mentions: All gels formed in the dissolution media were highly viscous and did not flow visibly when tilted. Clear gels were formed in buffered solution and FaSSIF, whereas gels in FeSSIF were slightly turbid. This agrees with the results and discussion above and it can be hypothesized that NaTC and lecithin formed large mixed aggregates in the gel, which scatter light. Interestingly, if SDS was added to the gels (in a similar ratio as in the tablets, see below) the turbidity of the FeSSIF gels decreased, probably due to solubilisation of lecithin. As can be seen the rheology of FaSSIF and FeSSIF gels differed significantly but when SDS is added this variation is considerably decreased, Fig 5.

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.