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.


Percentage of thalidomide retained on (ADHERED) and removed from the mucosa surface (NON ADHERED) after 3 min washing in 45 ml of simulated nasal fluid. The non adhered amounts were recovered as dispersed solid or in solution in the washing fluid; mean ± S.D., n = 3–4. *p < 0.05 according to unpaired two-tailed Student’s t-test.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

fig0030: Percentage of thalidomide retained on (ADHERED) and removed from the mucosa surface (NON ADHERED) after 3 min washing in 45 ml of simulated nasal fluid. The non adhered amounts were recovered as dispersed solid or in solution in the washing fluid; mean ± S.D., n = 3–4. *p < 0.05 according to unpaired two-tailed Student’s t-test.

Mentions: For the three formulations, the average percentage of THAL retained on the mucosa surface after the washing procedure with the simulated nasal fluid (ADHERED) and the drug amounts not retained and recovered in the removed solid or dissolved in the fluid (NON ADHERED) are shown in Fig. 6. To reveal a possible time dependency of mucoadhesion, the product was removed from the mucosa by washing three times at 1 min intervals. It was found that the lower the thalidomide dissolution rate in water, the greater the mucoadhesion. Indeed, 50% of the β-cyclodextrin powder was still retained on the mucosa surface after the washing. This was the same powder enabling the highest thalidomide accumulation within the mucosal tissue (see Fig. 5). As the more hydrophilic HP-β-CD and SBE-β-CD increased wettability and dissolution rate in aqueous media, the corresponding nasal powders more easily lost the contact with the mucosa and were removed. The respective adhered amounts were not significantly different (p = 0.16). The solid material physically detached from the mucosa remained dispersed or dissolved in the washing liquid phase. In fact, between 4% (β-CD powder) and 16% (HP-β-CD powder) of removed thalidomide was found in solution. Thus, dissolution by the washing fluid was mostly relevant for the most soluble HP-β-CD powder (p < 0.05 vs SBE-β-CD powder).


Nasal powders of thalidomide for local treatment of nose bleeding in persons affected by hereditary hemorrhagic telangiectasia
Percentage of thalidomide retained on (ADHERED) and removed from the mucosa surface (NON ADHERED) after 3 min washing in 45 ml of simulated nasal fluid. The non adhered amounts were recovered as dispersed solid or in solution in the washing fluid; mean ± S.D., n = 3–4. *p < 0.05 according to unpaired two-tailed Student’s t-test.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

fig0030: Percentage of thalidomide retained on (ADHERED) and removed from the mucosa surface (NON ADHERED) after 3 min washing in 45 ml of simulated nasal fluid. The non adhered amounts were recovered as dispersed solid or in solution in the washing fluid; mean ± S.D., n = 3–4. *p < 0.05 according to unpaired two-tailed Student’s t-test.
Mentions: For the three formulations, the average percentage of THAL retained on the mucosa surface after the washing procedure with the simulated nasal fluid (ADHERED) and the drug amounts not retained and recovered in the removed solid or dissolved in the fluid (NON ADHERED) are shown in Fig. 6. To reveal a possible time dependency of mucoadhesion, the product was removed from the mucosa by washing three times at 1 min intervals. It was found that the lower the thalidomide dissolution rate in water, the greater the mucoadhesion. Indeed, 50% of the β-cyclodextrin powder was still retained on the mucosa surface after the washing. This was the same powder enabling the highest thalidomide accumulation within the mucosal tissue (see Fig. 5). As the more hydrophilic HP-β-CD and SBE-β-CD increased wettability and dissolution rate in aqueous media, the corresponding nasal powders more easily lost the contact with the mucosa and were removed. The respective adhered amounts were not significantly different (p = 0.16). The solid material physically detached from the mucosa remained dispersed or dissolved in the washing liquid phase. In fact, between 4% (β-CD powder) and 16% (HP-β-CD powder) of removed thalidomide was found in solution. Thus, dissolution by the washing fluid was mostly relevant for the most soluble HP-β-CD powder (p < 0.05 vs SBE-β-CD powder).

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 &beta;-CD or its more hydrophilic derivatives such as hydropropyl-&beta;-CD and sulphobutylether-&beta;-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&ndash;3% of the thalidomide applied on the nasal mucosa was accumulated within the tissue, particularly with the &beta;-CD nasal powder.

No MeSH data available.