Characterization of lung-delivered in-situ forming controlled release formulations.
OBJECTIVE
This study investigated the controlled drug release potential of formulations revealing temperature-induced sol-gel transition following administration to the respiratory tract.


METHODS
Diverse sildenafil-containing aqueous poloxamer 407 preparations were evaluated for critical gelation temperature and rheological properties. The in-vitro drug release profiles of the in-situ forming formulations were studied in a Franz type cell, while the drug absorption characteristics were determined in an isolated lung model. Furthermore, the weight gain of isolated lungs was monitored and the bronchoalveolar lavage fluid was analysed for the total protein content.


RESULTS
Poloxamer 407 solutions with concentrations of >12 wt.% revealed gelation upon temperature increase (>20°C). Compared with free sildenafil solution, sildenafil-containing polymer formulations showed a prolonged in-vitro drug release profile. Likewise, 17 and 21 wt.% of poloxamer 407 were characterized by a sustained sildenafil transfer from the lung into the perfusate. However, a 10 wt.% polymer solution displayed an immediate sildenafil absorption. Interestingly, increasing the poloxamer 407 concentration (21 and 17 vs. 10 wt.%) led to decreased organ weight gain kinetics and a lower total protein content found in the bronchoalveolar lavage fluid.


CONCLUSIONS
In-situ forming controlled release hydrogels represent a viable approach for inhalative therapy.
Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
Alexandra C
AC
Dalla-Bona
Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
Katharina
K
Stoisiek
Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
Nina
N
Oesterheld
Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
Thomas
T
Schmehl
Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
Tobias
T
Gessler
Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
Werner
W
Seeger
Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
Moritz
M
Beck-Broichsitter
D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D020100:Hydrogels; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D020442:Poloxamer / Q000737:chemistry*; D011817:Rabbits; D012212:Rheology; D000068677:Sildenafil Citrate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D044366:Transition Temperature; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D014665:Vasodilator Agents; D020442:Poloxamer; D000068677:Sildenafil Citrate
controlled drug delivery; isolated rabbit lung; poloxamer 407; sildenafil; sol-gel transition