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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 measure elastic modulus (G’) at 0.2 Hz for homogeneous samples of polymer and lecithin, for 1 wt% Pemulen TR1 (filled square), TR2 (open squares).At lecithin concentrations above 5 mM the systems were not homogenous and were thus not subjected to further characterization. Carbopol, which lacks hydrophobes, formed heterogeneous samples at all concentrations with lecithin. The data points represent the mean values of three samples and error bars show the standard deviation (n = 3).
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pone.0140709.g004: The measure elastic modulus (G’) at 0.2 Hz for homogeneous samples of polymer and lecithin, for 1 wt% Pemulen TR1 (filled square), TR2 (open squares).At lecithin concentrations above 5 mM the systems were not homogenous and were thus not subjected to further characterization. Carbopol, which lacks hydrophobes, formed heterogeneous samples at all concentrations with lecithin. The data points represent the mean values of three samples and error bars show the standard deviation (n = 3).

Mentions: Mixtures with lecithin and Pemulen TR1 formed turbid, but macroscopically homogenous gels up to lecithin concentrations of ca. 5 mM. At higher concentrations, large, white lumps of lecithin were formed in the gel. The more hydrophobic material Pemulen TR2 formed a weakly turbid gel up to 5 mM lecithin. At higher concentrations, small white lumps could be observed in the gelatinous solution. The differences in turbidity may be correlated to a higher solubilising capacity of Pemulen TR2 towards lecithin where lecithin presumably was solubilised in the hydrophobic regions formed by association of the hydrophobes. In agreement with this idea, Carbopol 981 did not dissolve any lecithin and white lumps of lecithin were formed in the transparent gels already at low concentrations (1 mM). Rheological measurements were made on the homogenous samples containing lecithin and small amounts of lecithin improved the elastic properties of the HMPAA solutions in a similar manner as SDS and NaTC (Fig 4).


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 measure elastic modulus (G’) at 0.2 Hz for homogeneous samples of polymer and lecithin, for 1 wt% Pemulen TR1 (filled square), TR2 (open squares).At lecithin concentrations above 5 mM the systems were not homogenous and were thus not subjected to further characterization. Carbopol, which lacks hydrophobes, formed heterogeneous samples at all concentrations with lecithin. The data points represent the mean values of three samples and error bars show the standard deviation (n = 3).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140709.g004: The measure elastic modulus (G’) at 0.2 Hz for homogeneous samples of polymer and lecithin, for 1 wt% Pemulen TR1 (filled square), TR2 (open squares).At lecithin concentrations above 5 mM the systems were not homogenous and were thus not subjected to further characterization. Carbopol, which lacks hydrophobes, formed heterogeneous samples at all concentrations with lecithin. The data points represent the mean values of three samples and error bars show the standard deviation (n = 3).
Mentions: Mixtures with lecithin and Pemulen TR1 formed turbid, but macroscopically homogenous gels up to lecithin concentrations of ca. 5 mM. At higher concentrations, large, white lumps of lecithin were formed in the gel. The more hydrophobic material Pemulen TR2 formed a weakly turbid gel up to 5 mM lecithin. At higher concentrations, small white lumps could be observed in the gelatinous solution. The differences in turbidity may be correlated to a higher solubilising capacity of Pemulen TR2 towards lecithin where lecithin presumably was solubilised in the hydrophobic regions formed by association of the hydrophobes. In agreement with this idea, Carbopol 981 did not dissolve any lecithin and white lumps of lecithin were formed in the transparent gels already at low concentrations (1 mM). Rheological measurements were made on the homogenous samples containing lecithin and small amounts of lecithin improved the elastic properties of the HMPAA solutions in a similar manner as SDS and NaTC (Fig 4).

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.