Design and evaluation of levodopa methyl ester intranasal delivery systems.
OBJECTIVE
This study aimed to examine the feasibility of nasal powder formulations for the delivery of levodopa (L-dopa) into the brain using highly water-soluble levodopa methyl ester hydrochloride (LDME).


METHODS
For designing nasal LDME powders, pH-rate stabilities of LDME in buffer solutions and their enzymatic degradations in rabbit nasal mucosal and serosal extracts were investigated. In vitro permeation studies were carried out with four LDME nasal powders.


RESULTS
LDME was degraded fast in weakly acidic and neutral solutions, but relatively stable in acidic solutions. In nasal extracts, LDME (50 and 200 μg/mL) was rapidly hydrolyzed, forming L-dopa, and there were no significant differences in first-order degradation rates between mucosal and serosal extracts. From the in vitro permeation studies, LDME powder formulations resulted in faster appearance rates (1.07 ± 0.39 mg/cm²/hr) of L-dopa than solution formulations (0.35 ± 0.08 mg/cm²/hr).


CONCLUSIONS
These results suggested that LDME nasal powder formulations could be useful delivery systems of L-dopa.
College of Pharmacy, Dongduk Women's University, Seoul 501-759, Korea.
In Koo
IK
Chun
Yeon Hong
YH
Lee
Kyung Eun
KE
Lee
Hye Sun
HS
Gwak
D000281:Administration, Intranasal; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D007980:Levodopa / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects; D011817:Rabbits; D012704:Serous Membrane / Q000187:drug effects; D013997:Time Factors
D000978:Antiparkinson Agents; D007980:Levodopa; C035420:levodopa methyl ester