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

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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.


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SEM images of (a) thalidomide raw material, (b) β-CD nasal powder, (c) HP-β-CD nasal powder and (d) SBE-β-CD nasal powder.
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fig0015: SEM images of (a) thalidomide raw material, (b) β-CD nasal powder, (c) HP-β-CD nasal powder and (d) SBE-β-CD nasal powder.

Mentions: Powder particle size, packing and flow are key properties in view of nasal dosage form manufacturing, delivered dose uniformity, aerodynamic behaviour during insufflation, dissolution rate and interaction with the wet mucosa. Particle size analysis by laser diffraction showed a mean volume diameter (Dv0.5) between 13 and 22 μm for all powders (Table 2). This size was also confirmed by SEM analysis (Fig. 3). The particle shape of kneaded products appears as agglomerates with sharp edges, resulting from the sieve comminution after drying. Nevertheless, this non spherical morphology did not negatively affect powder flow and packing. Bulk density and repose angle values of these nasal powders allowed for classifying the formulations containing β-CD and HP-β-CD as free-flowing according to the Pharmacopoeia (Table 2). The SBE-β-CD nasal powder had inferior flow properties and looser packing.


Nasal powders of thalidomide for local treatment of nose bleeding in persons affected by hereditary hemorrhagic telangiectasia
SEM images of (a) thalidomide raw material, (b) β-CD nasal powder, (c) HP-β-CD nasal powder and (d) SBE-β-CD nasal powder.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

fig0015: SEM images of (a) thalidomide raw material, (b) β-CD nasal powder, (c) HP-β-CD nasal powder and (d) SBE-β-CD nasal powder.
Mentions: Powder particle size, packing and flow are key properties in view of nasal dosage form manufacturing, delivered dose uniformity, aerodynamic behaviour during insufflation, dissolution rate and interaction with the wet mucosa. Particle size analysis by laser diffraction showed a mean volume diameter (Dv0.5) between 13 and 22 μm for all powders (Table 2). This size was also confirmed by SEM analysis (Fig. 3). The particle shape of kneaded products appears as agglomerates with sharp edges, resulting from the sieve comminution after drying. Nevertheless, this non spherical morphology did not negatively affect powder flow and packing. Bulk density and repose angle values of these nasal powders allowed for classifying the formulations containing β-CD and HP-β-CD as free-flowing according to the Pharmacopoeia (Table 2). The SBE-β-CD nasal powder had inferior flow properties and looser packing.

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