TY - JOUR
T1 - Fenoldopam mesylate for treating psoriasis
T2 - A new indication for an old drug
AU - Doppalapudi, Sindhu
AU - Jain, Anjali
AU - Khan, Wahid
AU - Domb, Abraham J.
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2020/1/5
Y1 - 2020/1/5
N2 - Fenoldopam, a highly selective dopamine receptor agonist, is available in clinics as Corlopam™ i.v. for the management of severe hypertension. Recent reports demonstrate its anti-proliferative activity in vitro in a dose dependent manner. However, stability issues of the drug due to its susceptibility to oxidation, pH sensitivity, poor transdermal flux, and the barrier properties of skin present challenges to develop a topical formulation of fenoldopam. The aim of the present study is to suggest a stable topical formulation of fenoldopam for the treatment of psoriasis. Water washable ointment and glycerin-based carbopol anhydrous gel of fenoldopam intended for topical delivery were prepared and evaluated in vitro and in vivo. Results from pH dependent stability studies suggest the necessity to maintain acidic pH in final formulations. The presence of an acidic adjuster in ointment and unneutralised carbopol dispersion of anhydrous gel maintain the desired acidic environment in the formulations. Stability studies of prepared formulations performed for 90 days indicate that the drug remains stable in formulations. In vivo studies demonstrate the applicability of the formulations for better skin penetration, skin compliance, and photosafety. Efficacy studies using an imiquimod induced psoriasis model confirm the promising application of developed fenoldopam topical formulations for psoriasis.
AB - Fenoldopam, a highly selective dopamine receptor agonist, is available in clinics as Corlopam™ i.v. for the management of severe hypertension. Recent reports demonstrate its anti-proliferative activity in vitro in a dose dependent manner. However, stability issues of the drug due to its susceptibility to oxidation, pH sensitivity, poor transdermal flux, and the barrier properties of skin present challenges to develop a topical formulation of fenoldopam. The aim of the present study is to suggest a stable topical formulation of fenoldopam for the treatment of psoriasis. Water washable ointment and glycerin-based carbopol anhydrous gel of fenoldopam intended for topical delivery were prepared and evaluated in vitro and in vivo. Results from pH dependent stability studies suggest the necessity to maintain acidic pH in final formulations. The presence of an acidic adjuster in ointment and unneutralised carbopol dispersion of anhydrous gel maintain the desired acidic environment in the formulations. Stability studies of prepared formulations performed for 90 days indicate that the drug remains stable in formulations. In vivo studies demonstrate the applicability of the formulations for better skin penetration, skin compliance, and photosafety. Efficacy studies using an imiquimod induced psoriasis model confirm the promising application of developed fenoldopam topical formulations for psoriasis.
KW - Fenoldopam
KW - Imiquimod induced psoriasis model
KW - Psoriasis
KW - Skin penetration
KW - Stability
KW - Topical delivery
UR - http://www.scopus.com/inward/record.url?scp=85076202758&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2019.118726
DO - 10.1016/j.ijpharm.2019.118726
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C2 - 31715365
AN - SCOPUS:85076202758
SN - 0378-5173
VL - 573
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 118726
ER -