Preparation And Evaluation Of Simethicone Suspension

Simethicone is a complex of polydimethylsiloxane(PDMS)and colloidal silica(SiO2).It can be taken orally and not absorbed by the gastrointestinal tract.It is mainly used to treat symptoms caused by excessive gas in the gastrointestinal tract,for example,abdominal distension in children and adults caused by dyspepsia(food,changes in digestive enzymes,dysbacteriosis,bile secretion and other factors affecting absorption function).It can also be used before gastrointestinal endoscopy to significantly improve the effect of intestinal cleaning,improve gastrointestinal endoscopy images,improve the detection rate of lesions,improve the accuracy of the examination.In addition,studies have shown that simethicone can also promote the discharge of gas in the gastrointestinal tract of parturients after gynecological and obstetric surgery,and play a positive role in promoting the recovery of parturients after surgery.The action mechanism of simethicone is to break up the bubbles by reducing the surface tension of the bubbles,and then discharge the gas out of the body through absorption of the gastrointestinal wall or peristalsis of the gastrointestinal wall.After oral administration,it is directly excreted from the body as a prototype without absorption,distribution and metabolism.Simethicone does not interact with any drugs,and no side effects on human and animals have been found.Therefore,simethicone can be safely and widely used in some special patients,such as infants,pregnant women,surgical patients and the elderly patients.At present,the prescriptions of simethicone listed abroad include chewable tablets,capsules,emulsions and suspensions,while only emulsions are listed in the domestic market,which is simethicone emulsion produced by Berlin-Chemie AG in Germany(trade name:Boxi).There is no market preparation of simethicone suspension in China.In this paper,simethicone was prepared into suspension agent,which provided experimental basis for increasing the development of drug dosage form of simethicone.The research content of this subject is divided into the following parts:The first part is the quality analysis of Infacol.The appearance of Infacol is a white,low-viscosity suspension with orange flavor.Its viscosity is about 200 CP.Its particle size is D10≈ 5 micron,D50≈30 micron,D90≈75 micron.Its defoaming ability is about 95%.There is no stratification at the speed of 2000 rpm centrifugation for 6 minutes.Its pH is 3.15.Relative density is 1.0063 g/mL.Therefore,the key quality properties of self-made simethicone suspension should be similar to Infacol.The content of saccharin sodium in Infacol is 0.01%by high performance liquid chromato graphy.The second part is about the prescription and technology of simethicone suspension.According to the instructions of Infacol,the content of simethicone in Infacol is 40 mg/mL.The excipients contained flavoring agents are saccharin sodium and orange flavor,suspending agent is HPMC,preservatives are methyl hydroxybenzoate(E218)and propyl hydroxybenzoate(E216).The amount of HPMC was determined by controlling the viscosity of simethicone suspension.The type of HPMC was determined by determining the key quality attributes of simethicone suspension.The preparation process of simethicone suspension was determined by influencing factors experiment and controlling key quality attributes.Three batches of simethicone suspensions were prepared by optimum formulation and preparation process,and their key quality properties were compared with those of the original formulation.The third part is about the content and limit of the related substances in simethicone suspension.The related substances in simethicone suspension mainly include four kinds of cyclic siloxane and six kinds of linear siloxane.Cyclic siloxane in the simethicone suspension include:hexamethylcyclotrisiloxane,octamethylcyclotetrasiloxane,decamethylcyclopentasiloxane and dodecamethylcyclohexasiloxane.Linear siloxane in the simethicone suspension include:hexamethyldisiloxane,octamethyltrisiloxane,decamethyltetrasiloxane,dodecamethylpentosiloxane,tetramethylhexasiloxane and hexamethylheptasiloxane.In this chapter,tetrakis(trimethylsilyloxy)silane was used as internal standard to establish a method for the determination of related substances in simethicone suspension by gas chromatography,and the methodological validation of this method was carried out.The results show that the method has good specificity,recovery,replicate and robustness.Referring to the limit of impurity control of the preparation in technical guidelines for the study of impurities in chemical drugs,the limit of impurity in simethicone suspension should be less than 0.15%.The fourth part is about the determination of polydimethylsiloxane which is the main active ingredient in simethicone suspension.Referring to the determination method of polydimethylsiloxane content in registration standard for imported drugs of simethicone emulsion(JX20140233),a method for determination of polydimethylsiloxane content in simethicone suspension was established and validated.The results show that the method has good specificity,recovery,replicate and robustness.The fifth part is the establishment of quality standard for simethicone suspension and the determination of self-made samples.To establish the quality standard of simethicone suspension,including the determination of appearance,viscosity,particle size,defoaming,centrifugal stability,pH,relative density,related substances and polydimethylsiloxane content.Three batches of simethicone suspensions were prepared according to the optimal formulation and process.The key quality properties of the suspensions were determined and compared with the original preparation Infacol.The results showed that the key quality properties of self-made simethicone suspension were similar to those of Infacol.The sixth part is the pharmacodynamic experiment of simethicone suspension in mice.Firstly,mice were given excessive fructooligosaccharide solution to make models.Then the simethicone suspension was administered intragastrically.After a certain time of administration,the mice were killed by dislocation of neck,then the abdominal cavity was opened,the gastrointestinal tract was taken out,and the volume of the gastrointestinal tract was measured with a graduated cylinder.The pharmacodynamics of self-made simethicone suspension and Infacol in vivo was preliminarily investigated.The experimental results show that Infacol and self-made simethicone suspension have similar efficacy.