Complexation of the local anesthetic pramoxine with hydroxypropyl-beta-cyclodextrin can improve its bioavailability
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Journal of Drug Delivery Science and Technology
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Local anesthetics are widely used in clinical procedures, to eliminate pain during/after invasive procedures. A
wide range of drug delivery systems has been developed to improve the effect of local anesthetics and/or to
reduce their toxicity. Pramoxine (PMX) is a topical anesthetic agent with an unusual (morpholine ring) structure
and low solubility (ca. 3 mM at pH 7.4). In this work, a novel formulation was devised for PMX in hydroxypropyl-
β-cyclodextrin (HP-β-CD). Host-guest inclusion complex was prepared by the co-solubilization method,
with complexation kinetics of 10 h, and 1:1 PMX/HP-β-CD stoichiometry. Complexation promoted 14-fold increase
in the solubility of PMX. X-ray diffraction measurements revealed loss of the crystalline PMX pattern in
the presence of HP-β-CD, an indication of inclusion complexation. Using 1H NMR (DOSY) experiments the association
constant of PMX to HP-β-CD (Ka = 923.1 mol/L) was determined, while nuclear Overhauser (ROESY)
analysis confirmed the formation of PMX/HP-β-CD inclusion complex, by detection of spatial proximities between
hydrogens from PMX aromatic ring and cyclodextrin's cavity. In two in vitro toxicity models (mouse 3T3
fibroblasts in culture and red blood cells hemolysis) pramoxine toxicity was significantly reduced upon complexation
into HP-β-CD. These results point out PMX/HP-β-CD as a promising pharmaceutical formulation to
improve the bioavailability of pramoxine, allowing its application beyond topical anesthesia.
Como referenciar
BEZAMAT, JULIANA M.; YOKAICHIYA, FABIANO; FRANCO, MARGARETH K.K.D.; CASTRO, SIMONE R.; PAULA, ENEIDA de; CABEÇA, LUIS F. Complexation of the local anesthetic pramoxine with hydroxypropyl-beta-cyclodextrin can improve its bioavailability. Journal of Drug Delivery Science and Technology, v. 55, p. 1-8, 2020. DOI: 10.1016/j.jddst.2019.101475. Disponível em: http://repositorio.ipen.br/handle/123456789/31079. Acesso em: 30 Dec 2025.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.