Enhancement of levodopa stability when complexed with β-cyclodextrin in transdermal patches.
Levodopa is a promising candidate for administration via the transdermal route because it exhibits a short plasma half-life and has a small window of absorption in the upper section of the small intestine. The aim of this study was to prepare stable levodopa transdermal patches. Both xanthan gum and Carbopol 971 polymers were selected with ethylcellulose constituting the backing layer of the prepared patches. The effect of adding β-cyclodextrin on the prepared patches was investigated. The uniformity in thickness, weight and content of the studied patches was acceptable. Physicochemical characterization revealed that there was no interaction between levodopa and the applied polymer. The results proved that levodopa precipitated as an amorphous form in carbopol patches. Controlled drug release was achieved for all the tested patches over a 6 h period. However, increased permeation was achieved for the carbopol patches. Although cyclodextrin did not enhance levodopa permeation, the stability study confirmed that levodopa stability was enhanced when complexed with β-cyclodextrin. The cumulative amount of drug released from carbopol patches is slightly higher than that of xanthan patches. The optimal stability was achieved in the carbopol/levodopa:β-cyclodextrin patch. The levodopa-β-cyclodextrin complex was successfully characterized using X-ray diffraction, NMR analysis and molecular dynamics simulations. In conclusion, carbopol/levodopa:β-cyclodextrin patches can be considered as a promising stable and effective transdermal drug-delivery system.
a Jordan University of Science and Technology , Irbid , Jordan.
Rana
R
Obaidat
a Jordan University of Science and Technology , Irbid , Jordan.
Nizar
N
Al-Shar'i
a Jordan University of Science and Technology , Irbid , Jordan.
Bassam
B
Tashtoush
a Jordan University of Science and Technology , Irbid , Jordan.
Tamara
T
Athamneh
D000179:Acrylates / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D000279:Administration, Cutaneous; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray / Q000379:methods; D004338:Drug Combinations; D004355:Drug Stability; D007980:Levodopa / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064449:Sequestering Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D057968:Transdermal Patch; D014961:X-Ray Diffraction / Q000379:methods; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism
D000179:Acrylates; D000978:Antiparkinson Agents; D004338:Drug Combinations; D011135:Polysaccharides, Bacterial; D064449:Sequestering Agents; D047392:beta-Cyclodextrins; C492577:carbopol 971P; D007980:Levodopa; C031215:betadex; C002563:xanthan gum
carbapol; levodopa; molecular dynamics simulations; transdermal; xanthan; β-Cyclodextrin