Study of insolubility problems of dexamethasone and digoxin: cyclodextrin complexation.
Cyclodextrins are able to form inclusion complexes with a number of drugs if their molecular dimensions correspond to those of the cyclodextrin cavity which leads to change of physicochemical and biopharmaceutical properties of drugs. 2-Hydroxypropyl beta cyclodextrin (HP beta CD) is suitable for parenteral application because of its considerable solubility in water and low hemolytic activity. Digoxin is insoluble in water, sensitive to light and is a subject of acidic hydrolysis, it is a challenge to the technologists of parenteral dosage forms. Dexamethasone (Dex) has a very small solubility in water (0.1 mg/ml), which caused troubles by preparing liquid medicine forms. The inclusion of hydroxy acids in CD-complexes in the necessary molar proportions leads to considerable increase in the solubility of a medicine and to several times decrease of the amount of CD used. Inclusion complexation was confirmed by the results from the studies of Differential Scanning Calorimetry. The present investigation demonstrated that Digoxin/CD complex shows stability in water medium and the optimum molar ratio Digoxin/HP beta CD is 1:6. The same results can be achieved through HP beta CD, by including Dex in a multicomponent composition containing HP beta CD and citric acid in a molar ratio of 1:4:1.
Dilova
V
V
Department of Galenical, Chemical Pharmaceutical Research Institute, Sofia, Bulgaria.
Zlatarova
V
V
Spirova
N
N
Filcheva
K
K
Pavlova
A
A
Grigorova
P
P
D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry*; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry*; D004077:Digoxin / Q000008:administration & dosage / Q000737:chemistry*; D004355:Drug Stability; D019999:Pharmaceutical Solutions; D012995:Solubility
D000889:Anti-Arrhythmia Agents; D000893:Anti-Inflammatory Agents; D003505:Cyclodextrins; D019999:Pharmaceutical Solutions; D004077:Digoxin; D003907:Dexamethasone