Limits...
Nasal powders of thalidomide for local treatment of nose bleeding in persons affected by hereditary hemorrhagic telangiectasia

View Article: PubMed Central - PubMed

ABSTRACT

In this work nasal powder formulations of thalidomide were designed and studied to be used by persons affected by hereditary hemorrhagic telangiectasia as a complementary anti-epistaxis therapy, with the goal of sustaining the effect obtained with thalidomide oral treatment after its discontinuation for adverse effects. Three nasal powders were prepared using as carriers β-CD or its more hydrophilic derivatives such as hydropropyl-β-CD and sulphobutylether-β-CD and tested with respect to technological and biopharmaceutical features after emission with active and passive nasal powder devices. For all formulated powders, improved dissolution rate was found compared to that of the raw material, making thalidomide promptly available in the nasal environment at a concentration favouring an accumulation in the mucosa. The very limited transmucosal transport measured in vitro suggests a low likelihood of significant systemic absorption. The topical action on bleeding could benefit from the poor absorption and from the fact that about 2–3% of the thalidomide applied on the nasal mucosa was accumulated within the tissue, particularly with the β-CD nasal powder.

No MeSH data available.


Related in: MedlinePlus

Dissolution profiles of (○) thalidomide raw material, (□) β-CD nasal powder, (△) HP-β-CD nasal powder and (◊) SBE-β-CD nasal powder (mean ± S.D.; n = 3).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5120990&req=5

fig0020: Dissolution profiles of (○) thalidomide raw material, (□) β-CD nasal powder, (△) HP-β-CD nasal powder and (◊) SBE-β-CD nasal powder (mean ± S.D.; n = 3).

Mentions: In these conditions only 46.0 ± 0.1% of thalidomide raw material dissolved in 1 h, reaching 72.0 ± 0.9% at the end of the second hour (Fig. 4). It was observed that during the first minute drug powder floated on the dissolution medium surface, owing to its difficult wettability. In contrast, kneaded powders containing cyclodextrins together with lecithin dissolved more rapidly, reaching 84 ± 1%, 99 ± 2% and 93 ± 2% respectively of thalidomide in solution after 60 min. for the powder containing β-CD, HP-β-CD and SBE-β-CD. This improvement in drug dissolution rate had two main explanations. Firstly, solid state analysis of the powders showed that thalidomide and cyclodextrins partially interacted. This interaction at the molecular level increased the drug solubility in aqueous environment (as demonstrated in the phase solubility studies). The second positive contribution to thalidomide dissolution rate came from lecithin, owing to its surface-active properties. The positive effect of lecithin on wettability increased the powder surface interacting with the solvent.


Nasal powders of thalidomide for local treatment of nose bleeding in persons affected by hereditary hemorrhagic telangiectasia
Dissolution profiles of (○) thalidomide raw material, (□) β-CD nasal powder, (△) HP-β-CD nasal powder and (◊) SBE-β-CD nasal powder (mean ± S.D.; n = 3).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120990&req=5

fig0020: Dissolution profiles of (○) thalidomide raw material, (□) β-CD nasal powder, (△) HP-β-CD nasal powder and (◊) SBE-β-CD nasal powder (mean ± S.D.; n = 3).
Mentions: In these conditions only 46.0 ± 0.1% of thalidomide raw material dissolved in 1 h, reaching 72.0 ± 0.9% at the end of the second hour (Fig. 4). It was observed that during the first minute drug powder floated on the dissolution medium surface, owing to its difficult wettability. In contrast, kneaded powders containing cyclodextrins together with lecithin dissolved more rapidly, reaching 84 ± 1%, 99 ± 2% and 93 ± 2% respectively of thalidomide in solution after 60 min. for the powder containing β-CD, HP-β-CD and SBE-β-CD. This improvement in drug dissolution rate had two main explanations. Firstly, solid state analysis of the powders showed that thalidomide and cyclodextrins partially interacted. This interaction at the molecular level increased the drug solubility in aqueous environment (as demonstrated in the phase solubility studies). The second positive contribution to thalidomide dissolution rate came from lecithin, owing to its surface-active properties. The positive effect of lecithin on wettability increased the powder surface interacting with the solvent.

View Article: PubMed Central - PubMed

ABSTRACT

In this work nasal powder formulations of thalidomide were designed and studied to be used by persons affected by hereditary hemorrhagic telangiectasia as a complementary anti-epistaxis therapy, with the goal of sustaining the effect obtained with thalidomide oral treatment after its discontinuation for adverse effects. Three nasal powders were prepared using as carriers β-CD or its more hydrophilic derivatives such as hydropropyl-β-CD and sulphobutylether-β-CD and tested with respect to technological and biopharmaceutical features after emission with active and passive nasal powder devices. For all formulated powders, improved dissolution rate was found compared to that of the raw material, making thalidomide promptly available in the nasal environment at a concentration favouring an accumulation in the mucosa. The very limited transmucosal transport measured in vitro suggests a low likelihood of significant systemic absorption. The topical action on bleeding could benefit from the poor absorption and from the fact that about 2–3% of the thalidomide applied on the nasal mucosa was accumulated within the tissue, particularly with the β-CD nasal powder.

No MeSH data available.


Related in: MedlinePlus