Formulation And Studies Of Tongshu Suppository

Objectives: With the illness, pain syndrome is a prevalent condition inclinical departments.influencing the life quality of patient severely. Currentlysymptomatic treatment for pain is the common way, and nonsteroidalanti-inflammatory drugs were used usually, Chlorine vinegar Finnacid(Aceclofenac, ACF) belong to nonsteroidal anti-inflammatory drug andwas moderate cox-2inhibitor, it had lower incidence of gastrointestinal sideeffects, cardiovascular events, but the listing of dosage form only had tabletsand capsules, and gastrointestinal reaction had occurred, such as nausea,dyspepsia, peptic ulcer and so on. This research would like to use the doubleimmune regulation on the gastrointestinal and anti-arthritis of astragaluspolysaccharide (APS), with ACF made from mixing suppository. Through theaddtion of APS and change the drug delivery route，make the gastrointestinalreaction lower. Tongshu suppository could further enhance the security andimprove patient compliance.Methods:1Preparation of Tongshu suppository：Tongshu suppository was preparedby hot melt with polyethylene glycol4000, glycol4000and glycerin:(a)Weighted a certain amount of ACF and APS and through100mesh sieverespectively with sufficient mixing.(b) Polyethylene glycol400, polyethyleneglycol4000and glycerin were melted and stirring until full fusion.(c) Whenmatrix temptature fall to proper state, willed A to B in less frequent way,stirring fully and mixing dispersed uniformly in the matrix, it was until cooledto preference state that we poured it into suppository mode.(d) After cooledand frozen, shaved the surface leveling and demoulded. The prescription ofsuppository was determined by a series of single factor experiments, and thedemould properties,appearance and dissolution was taken as a evaluationindex. Through L9(33) orthogonal experimental design to screen the best preparation.2Research on quality control about Tongshu suppository: establishedUV-visible spectrophotometry for the determination of dissolution of Tongshusuppository; Established HPLC method for the determination of contect andcontent uniformity. The methodological studies were carried out. PreparedTongshu suppository in accordance with the best prescription, and studied thestability of the preparation with the evaluation indexes of appearance, contentand dissolution. Stress testing and accelerated testing were also carried out.3Tongshu suppository pharmacokinetic research: A HPLC method wasdeveloped for the determination of Tongshu suppository in New Zealandrabbits plasma. New Zealand rabbit as experimental animals, examined theTongshu suppository pharmacokinetic, Aceclofenac was taken as the referencepreparation, a single-dose, two-treatment, two-sequence and randomizedcrossover study was carried out on four New Zealand rabbits, and studying itspharmacokinetic parameters,bioavailability and bioequivalence.Result:1According to the demould properties, appearance and dissolutionresults, The best prescription of the Tongshu suppository were selectedthrough the single factor test and factorial experimen design. Each Aceclifenac100mg, APS100mg, PEG4000475mg, PEG400475mg, glycerin100mg,each bolt weighs about1250mg.2Established a UV-visible spectrophotometry method for thedetermination of dissolution rate of Tongshu suppository. The detectionwavelength was273nm with no interference of excipient in phosphate buffer(pH6.8). The methodological study results showed that within theconcentration range of10.16μg·mL-1～40.64μg·mL-1, the linear relationshipbetween absorbance and concentration of ACF was good. The regressionequation was A=0.0246+0.0192C, correlation coefficient γ=0.9994, RSDprecision value was0.17%, low, medium, and high concentrations ofrecoveries mean of100.2%. This method can be used for the determination ofthe dissolution of Tongshu suppository. 3Established the HPLC method d for the determination of content ofTongshu suppository.The detection wavelength of273nm with no interferenceof excipient and acetonitrile. The methodological study results showed thatwithin the concentration range of5.08μg·mL-1～101·6μg·mL-1range, thelinear relationship between peak area and concentration of ACF was good,and precision, stability and recovery rate meeted the requirements of themethodology.4Study on stability of Self-made Tongshu suppository: under thecondition of temperature(60℃), the suppository would soon melt and darker,under the condition of high temperature40℃，the apperance and content ofACF had no change；Under the condition of strong light (4500lx±500lx),there was no significant change in the content and apperance. under thecondition of high humidity, the surface moisture, and precipitation with a layerof white matter, but the content had no obvious changes, the stability testshowed that self-made preparation were sensitive to the temperature, humidity,temperature, should be placed away from light, moisture, under the conditionof low temperature preservation.5Established a HPLC method for determination of Aceclofenac blooddrug concentration, The detection wavelength of273nm with blank plasma nointerference, self-made bolt AUC0-upthan reference preparation increased, therelative bioavailability F is104.4%.Conclusion:The formulation and preparation of Tongshu suppository was simple andfeasible, with good reproducibility, and could be avoid the oral dosing ofgastrointestinal stimulation and improve patients medication compliance. Themethods have established for the determination of content and dissolution. theconcentration of plasma drug concentration determination method wasestablished, for the study of the preparation of quality guarantee. Tongshusuppository should be kept low temperature away from light moisture; Vivopharmacokinetic studies have shown that the bioavailability of self-made thanreference preparation have increased.