Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. 4. Chlorpromazine hydrochloride.
The potentiality of interaction of chlorpromazine hydrochloride (CPZ) with beta-cyclodextrin (beta-CD) was investigated by spectrophotometry, vapour pressure osmometry and DSC thermograms. The results revealed a very strong evidence for molecular interaction between CPZ and beta-CD. The continuous variation method was used to elucidate the stoichiometry of such interaction by spectrophotometric as well as vapour pressure measurements. Both types of data revealed the formation of a 1:1 complex. The stability constant of the complex was determined at different temperatures by the vapour pressure osmometric method. The enthalpy and entropy of interaction were evaluated and the results indicate that the interaction is exothermic. The CPZ/beta-CD complex was prepared, lyophilized and photochemical stability of the drug, its physical mixture with beta-CD as well as the prepared complex was investigated at different pH-values in presence of different buffer systems. The results revealed that the stability of the drug is greatly improved in presence of beta-CD and the great dependency of stability on the pH of the solution is decreased in presence of beta-CD. The partition coefficient of CPZ and its complex with beta-CD was determined. The data reveal a higher p.c. of the complex compared to the parent drug. The effect of beta-CD on the bioavailability of CPZ was investigated by measuring the miotic response intensity in volunteers receiving a single oral dose of the drug, drug/beta-CD physical mixture or complex. The results revealed a distinct improvement of the biological performance of CPZ by beta-CD as evidenced by an increased intensity of drug action and its duration as well as augmenting its bioavailability without affecting the time for maximum effect.
Ammar
H O
HO
Department of Pharmaceutical Sciences, National Research Center, Dokki, Cairo, Egypt.
Ghorab
M
M
el-Nahhas
S A
SA
Omar
S M
SM
Ghorab
M M
MM
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002746:Chlorpromazine / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D003505:Cyclodextrins / Q000737:chemistry*; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008916:Miotics / Q000494:pharmacology; D010777:Photochemistry; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D014835:Volatilization
D014150:Antipsychotic Agents; D003505:Cyclodextrins; D008916:Miotics; D002746:Chlorpromazine