Preparation And Characterization Of The Inclusion Complexes Of Terbinafine Hydrochloride With Hydroxypropyl-β-Cyclodextrin

Terbinafine hydrochloride(TFH)is a synthetic allylamine derivative,which has the advantages of low toxicity and good tolerability.It can be used to treat skin fungal infections and is widely used in the clinical treatment of various skin tinea,onychomycosis and Candida infections.However,the solubility of TFH in water is very low.It is very important to develop new water-soluble dosage forms of TFH to solve this problem.Hydroxypropyl-β-cyclodextrin(HP-β-CD)is a kind of cyclodextrin derivative transformed fromβ-cyclodextrin.Introducing hydroxypropyl into cyclodextrin increases its water solubility.HP-β-CD present a hollow torus structure,hydrophilic outside and hydrophobic inside,so it is often used as a drug carrier to encapsulate drug molecules in its hydrophobic cavity to change some of the properties of drug molecules.In addition,the low toxicity and excellent biocompatibility of HP-β-CD make the inclusion complexes have wide applications in cosmetic,pharmaceutical,medical,food industry and electronic technology fields.In this study,HP-β-CD was used as a drug carrier package to prepare TFH/HP-β-CD inclusion complex,which finally improved the water solubility of the drug,.And it provided new ideas for the development of new dosage forms of TFH.The contents and results of the experiment are as follows:(1)The method of TFH quantitative analysis was established by ultraviolet and visible spectrophotometerFirst,Detection of TFH absorbance at wavelength 223 nm was determined by scanning with a UV-Vis spectrophotometer.Therefore,at the wavelength,the concentration of TFH is used as the Abscissa and the absorbance as the ordinate to establish the regression curve,the regression equation is y=0.2958x+0.0264,R~2=0.9997.This method can quickly determine the concentration of TFH with high stability,good repeatability and high recovery.It can be used to detect the content of TFH in subsequent experiments.(2)Preparation and optimization of TFH/HP-β-CD inclusion complexIn this study,TFH/HP-β-CD inclusion complex was prepared by solution stirring method and ultrasonic method.Using single factor investigation and orthogonal experiment,the conditions of the two preparation methods were optimized respectively.The results are as follows:The influence of the four factors in the preparation of inclusion complexes by solution stirring method and ultrasonic method are in order:molar ratio,temperature,ultrasonic time,and amount of water added.And the optimum preparation conditions of solution stirring method are as follows:the molar ratio of TFH/HP-β-CD is 1:1,the temperature is 40℃,the stirring time is 1 h,the amount of water is 10 ml.The optimum preparation conditions of ultrasonic method are as follows:the molar ratio of TFH/HP-β-CD is 1:1,the temperature is 40℃,the ultrasonic time is2 h,and the amount of water is 7.5 ml.The preparation of inclusion complexes by ultrasonic method is superior to solution stirring method.(3)Analysis and characterization of TFH/HP-β-CD inclusion complexTFH and HP-β-CD were analyzed using phase solubility experiments to obtain a phase solubility curve of the A_Ltype,indicating that the two formed TFH/HP-β-CD inclusion complex in a molar ratio of 1:1.Determination of dissolution rate demonstrated a significant improvement in the water solubility of TFH/HP-β-CD complex compared with TFH.The structure of the inclusion complex was observed by scanning electron microscopy as an irregular flaky structure,which was different from the structure of TFH and HP-β-CD;There is only the absorption peak of HP-β-CD in the inclusion complex spectrum obtained by FTIR scanning,and the absorption peak of TFH disappears;Compared with the TFH spectrum,the absorption peak of the inclusion complex spectrum obtained by Raman spectroscopy is shifted to the right;The above characterization of the inclusion complex proves that the TFH/HP-β-CD inclusion complex was successfully prepared.Next,the molecular docking of terbinafine and HP-β-CD indicated that a stable complex was formed between terbinafine and HP-β-CD through hydrogen bonding and van der Waals force.In this study,the TFH/HP-β-CD inclusion complex was successfully prepared by solution stirring method and ultrasonic method to improve the poor water solubility of TFH.