Prolonged release of drug from O/w emulsion and residence in rat nasal cavity.
The present study evaluated the usefulness of an o/w emulsion for slowing the release of chlorpheniramine maleate (CM) and prolonging drug residence in the nasal cavity. O/w emulsion formulations of medium chain triglycerides (MCT) were prepared, and their physicochemical properties and drug release kinetics were evaluated using the in vitro dialysis tube method. Drug disappearance from the rat nasal cavity was determined in in situ nasal experiments. CM partitioned in oil droplets by pH, as predicted by pH partition theory. With higher MCT concentration and pH, slower release of CM was observed. CM disappearance (kapp) from the rat nasal cavity was influenced by the amount of drug partitioned in the oil droplets with both the perfusion and deposit methods, and the kapp of CM decreased with increase in MCT concentration and pH. Moreover, with the deposit method, CM remaining in the nasal cavity exhibited a biphasic profile of disappearance, which complied with a saturated process. Because a very small portion of MCT might be adsorbed and formed a pseudooily layer on the mucous membranes, prolongation of CM residence on the mucous membrane was attained. These findings suggest that emulsion containing 30% MCT at pH 8 may be useful for inclusion in controlled-release formulations of CM for intranasal drug delivery in the treatment of allergy.
Aikawa
K
K
Health Science R&D Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Matsumoto
K
K
Uda
H
H
Tanaka
S
S
Shimamura
H
H
Aramaki
Y
Y
Tsuchiya
S
S
D000281:Administration, Intranasal; D000818:Animals; D002744:Chlorpheniramine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004655:Emulsions; D006634:Histamine H1 Antagonists / Q000008:administration & dosage*; D006863:Hydrogen-Ion Concentration; D009297:Nasal Mucosa / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D003692:Delayed-Action Preparations; D004655:Emulsions; D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine