Abstract
Objective: Current work aimed to enhance solubility and stability of 5-fluorouracil drugs by preparing inclusion complex with β-cyclodextrin. Methods: In this study, inclusion complex preparation ratio selected on the basis of slope and Kc (binding constant) value in between 5-fluorouracil-β-cyclodextrin and best method out of the physical mixture, kneading method, and co-evaporation method for solubility and stability enhancement is selected on the basis of % yield, drug content, dissolution rate study and stability study. Results: Based on the phase solubility graph, a 1:1 ratio was selected for complex formation by Kc value which decided a quite stable form of a complex. The characterization of all three types of inclusion complex was performed by DSC and SEM. It proved that different moiety of the complex was formed, but all are quite stable with negligible interaction. The kneading method as the best inclusion complex at ratio 1:1 was selected after evaluating by performing percent yield and drug content and dissolution rate study for solubility profile and physical appearance, drug content, and drug release study for stability profile. Conclusion: We finally conclude that the Kc value proved that the inclusion complex is quite stable and ready to convert in any dosage form of choice. Inclusion complex formed by kneading method is one of the best options among all three techniques for solubility and stability enhancement of drug, which definitely help for a 5-fluorouracil drug to convert into a better dosage form to treat carcinoma.
Highlights
5-Fluorouracil (5-FU) is a drug that behaves as antimicrobial and broadspectrum antineoplastic agents
A phase solubility study was conducted for 5-fluorouracil drugs in distilled water containing different concentrations of β-cyclodextrin in moles; the whole criteria for phase solubility calculation were conducted according to the method explained by Higuchi and Conner’s
After seeing, which was framed in between solubility of fluorouracil and concentration of β-cyclodextrin plot, clearly observed that the aqueous solubility of 5-fluorouracil is directly proportional to the mole’s concentration of β-cyclodextrin. This linear motion of graph between the solubility of a 5-fluorouracil and concentration of β-cyclodextrin is not fully linear which proven that solubility of a 5-FU drug increases up to a limit in the presence of β-cyclodextrin and graph classified as B (BS type) curve, which means a limited solubility enhancement is obtained through inclusion complex [43]
Summary
5-Fluorouracil (5-FU) is a drug that behaves as antimicrobial and broadspectrum antineoplastic agents. It is basically a derivative of pyrimidine [1]. The 5-fluorouracil drug is very common when provided through intravenous route; this is because this drug is having few disadvantages when given through oral route like it is a sparingly soluble drug and having only 12 mg/ml solubility, cause gastrointestinal irritation during absorption, have a half-life of 10-20 min and cause severe level side effects [3, 4]. That’s why this is necessary to increase the drug solubility if we want to decrease the drug dose and dose-related side effects and to solve a problem; first of all we have to increase the solubility of the drug, which is a very common process for poorly soluble drugs. There are many alternatives to solve the problem of low solubility, like structure modification [5], co-solvency, the addition of surfactant [6, 7], drug encapsulation in carrier [8], reduction in particle size [9], drug complexation [10] and many more
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