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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.


Oscillation measurements at constant stress (1 Pa) of 1 wt% polymer gels in water at pH 6.From left to right Carbopol 981 (a), Pemulen TR 1 (b) and Pemulen TR 2 (c). The elastic (G’, filled squares) and viscous (G”, open squares) moduli are shown as functions of frequency.
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pone.0140709.g001: Oscillation measurements at constant stress (1 Pa) of 1 wt% polymer gels in water at pH 6.From left to right Carbopol 981 (a), Pemulen TR 1 (b) and Pemulen TR 2 (c). The elastic (G’, filled squares) and viscous (G”, open squares) moduli are shown as functions of frequency.

Mentions: Fig 1 show typical frequency sweeps of 1 wt% Pemulen TR1, Pemulen TR2 and Carbopol 981 in pure water at pH 6. In all cases, G’ is much higher than G” and shows no, or only minor, frequency dependence. This rheological fingerprint is typical for a gel. Pemulen TR1 has the highest G’ and G” values, whereas Pemulen TR 2, with its higher hydrophobicity, has lower G’ and G” values. The rheology of Carbopol 981 was similar to that of Pemulen TR2, while Pemulen TR1 gave a much stiffer gel.


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)

Oscillation measurements at constant stress (1 Pa) of 1 wt% polymer gels in water at pH 6.From left to right Carbopol 981 (a), Pemulen TR 1 (b) and Pemulen TR 2 (c). The elastic (G’, filled squares) and viscous (G”, open squares) moduli are shown as functions of frequency.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140709.g001: Oscillation measurements at constant stress (1 Pa) of 1 wt% polymer gels in water at pH 6.From left to right Carbopol 981 (a), Pemulen TR 1 (b) and Pemulen TR 2 (c). The elastic (G’, filled squares) and viscous (G”, open squares) moduli are shown as functions of frequency.
Mentions: Fig 1 show typical frequency sweeps of 1 wt% Pemulen TR1, Pemulen TR2 and Carbopol 981 in pure water at pH 6. In all cases, G’ is much higher than G” and shows no, or only minor, frequency dependence. This rheological fingerprint is typical for a gel. Pemulen TR1 has the highest G’ and G” values, whereas Pemulen TR 2, with its higher hydrophobicity, has lower G’ and G” values. The rheology of Carbopol 981 was similar to that of Pemulen TR2, while Pemulen TR1 gave a much stiffer gel.

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.