Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. 3. Bromhexine hydrochloride.
The potentiality of interaction of bromhexine (1) with beta-cyclodextrin was investigated by spectrophotometric methods. Differential UV spectrophotometry revealed a decrease in the optical density of the drug in presence of beta-cyclodextrin (beta-CD) and a hypsochromic shift in one of the two wavelengths of maximum absorption of the drug from 312 to 309 nm in presence of beta-CD. The continuous variation method based on spectrophotometric measurements revealed the formation of 1:1 complex between the drug and beta-CD. The solubility of 1 in presence of beta-CD was found to increase to a marked extent. Also the dissolution profiles of the drug, physical mixture of the drug and beta-CD as well as the prepared complex showed a great enhancement of the dissolution properties of 1 in presence of beta-CD either in a physical mixture or in complexed state. The partition coefficient between n-octanol and phosphate buffer of pH 7.4 of 1 and its beta-CD complex was also determined. Investigation of the transdermal diffusion of the drug and the complex in different dermatological vehicles was carried out using abdominal rat skin. A linear relationship was found to exist between the amount of drug released and the square root of the time. The drug showed the highest release characteristics from methyl cellulose > PVP > PEG 400, also inclusion complexation of 1 in beta-CD causes an improvement in the release properties of the drug from the investigated dermatological vehicles.
Ammar
H O
HO
Department of Pharmaceutical Sciences, National Research Center, Cairo, Egypt.
el-Nahhas
S A
SA
D000279:Administration, Cutaneous; D000818:Animals; D001964:Bromhexine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D003505:Cyclodextrins / Q000737:chemistry*; D004058:Diffusion; D008297:Male; D014677:Pharmaceutical Vehicles; D051381:Rats; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D003505:Cyclodextrins; D014677:Pharmaceutical Vehicles; D001964:Bromhexine