| Tanshinone are liposoluble components extracted from salvia miltiorrhiza. It has strong antiviral activity, but the water-solubility of tanshinone is very bad and its physical and chemical properties are not stable, which greatly limits its application in veterinary clinical application. R-beta-cyclodextrin is one kind of cyclodextrin derivatives which is commonly used as drug package material. This subject aims to prepare tanshinone-R-β-CD complex solution through the cyclodextrin inclusion method in order to solve its solubility and implement transformation of its dosage form. Based on the investigation to the tanshinone physical and chemical properties, this paper focus on studying various process parameters which can influence the preparation effect through single factor test and orthogonal test design.So that it can get the minimum dosage of cyclodextrins, the highest inclusion rate, better solubility, stable quality. Simply evaluating the quality of inclusion and preliminarily studying the controlling of inclusion quality by means of thin layer chromatography (TLC) and high performance liquid chromatography (HPLC).(1) HPLC method established for determination of tanshinone content in the solution of inclusion finds that tanshinone Ⅱ A mass concentration, from9.18to45.92ug/mL, has a good linear relationship (R2=0.9997), the average recovery of the method was97.53%and its RSD value was1.74%, the precision is high and its RSD value was1.21%; Cryptotanshinone mass concentration, from3.54to17.68ug/mL, has a good linear relationship (R2=0.9996), the average recovery was96.86%and its RSD value was1.14%, the precision is high and its RSD value was0.75%.(2) Single factor experiment studied various process parameters such as the ratio of cyclodextrins and drug, temperature, ethanol content, mixing time, stirring speed and PH. Cyclodextrin ratio has significant effect on the rate of inclusion and80-1can be set as the preliminary ratio; Heating is good for inclusion reaction and60℃can be set as guide temperature; Adding suitable amount of ethanol is good for drug dispersing into water which could be set at5%;Appropriately extending mixing time is beneficial to improve the effect of inclusion process and it can be set at6h.(3) Optimizing preparation technology parameters combination by L9(34) orthogonal experimental design and finally determining the optimal preparation process as follows:Ratio of cyclodextrin and tanshinone is80:1; Temperature for heating is60℃Concentration of ethanol is5%; Time for magnetic stirring is3h.(4) The solution of inclusion is simply quality evaluated which is a brownish red and transparency solution. Solubility of tanshinone Ⅱ A and cryptotanshinone of inclusion in water can reach0.38mg/mL and0.14mg/mL, total tanshinone’s inclusion solubility in water can reach1.32-1.82mg/mL, which is obviously enhanced.(5) Measuring NO.20130505, NO.20130505and NO.20130505tanshinone-R-β-CD complex solution, tanshinone ⅡA average content gets to290μg/mL. Cryptotanshinone average content gets to273μg/mL. The thin layer chromatography (TLC) successfully identified tanshinone-R-β-CD complex solution.To sum up, this experiment gets the tanshinone-R-β-CD complex solution in which less raw material is used, drug quality is more stable, inclusion rate is high and solubility of tanshinone get great improved and it also establishes the accurate tanshinone identification and content determination methods, completing the preliminary study on quality controlling. It can provide further help for this drug’s production process and clinic application... |
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