Permeation of quinine across sublingual mucosa, in vitro.
Quinine is the first line treatment in severe P. falciparum malaria and nocturnal leg cramps and a fast, convenient delivery method of this drug quinine is needed. The purpose of this study was to investigate in vitro the sublingual route for the delivery of quinine. Permeation studies were carried out with Franz diffusion cells containing sublingual mucosa membranes with PBS receptor phase and dosed with solutions of quinine hydrochloride or quinine/2-hydroxypropyl-beta-cyclodextrin complexes. Receptor phase samples were taken 2 hourly over a 12h period and quinine was determined by reverse-phase HPLC analysis. The ventral surface of the tongue was significantly more permeable than porcine floor of the mouth (p<0.05) and there was no significant effect of freezing on the ventral surface of the tongue (p 0.2444). The presence of saliva caused a decrease in the permeation of quinine across the ventral surface of the tongue by up to 68%. Inclusion complexation between quinine and 2-HP-beta-CD was supported by (1)H NMR spectral data, and an ethanol vehicle provided the highest quinine flux from the inclusion complex solutions compared to deionised water and PEG. Overall, the data support further investigations into the clinical use of sublingual quinine, particularly for children with falciparum malaria or patients with nocturnal leg cramps. Use of quinine/cyclodextrin inclusion complexes may circumvent compliance issues due to bitter taste.
Welsh School of Pharmacy, Cardiff University, Cardiff, UK.
Charlene M Y
CM
Ong
Charles M
CM
Heard
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000286:Administration, Sublingual; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002648:Child; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D009061:Mouth Mucosa / Q000378:metabolism; D010539:Permeability; D011803:Quinine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012463:Saliva / Q000378:metabolism; D013552:Swine; D014059:Tongue / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000962:Antimalarials; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011803:Quinine