Preliminary Pharmaceutical Research Of Simethicone Emulsion

Simethicone is a mixture of 90.5-99.0%polydimethylsiloxane(PDMS,also known as dimethicone)and 4.0～7.0%silicon dioxide(SiO2).Simethicone is a stable nonionic surfactant that reduces the surface tension of the bubbles,promotes bubble breakage,or binds to other bubbles in the gastrointestinal tract,making the bubbles more easily excreted.Clinically used mainly for the treatment of abdominal swelling.intestinal bloating,functional dyspepsia and irritable bowel syndrome etc.caused by excessive gas.Simethicone also be used to assist abdominal imaging,treat infants or young children feeding intolerance and postoperative abdominal pain.Many simethicone dosage forms,such as tablets,emulsions,suspensions,soft capsules and other preparations has been listed on abroad,but only simethicone emulsion(specifications for 40nig/ml.trade name Espumisan/Boxi)produced by the Berlin-Chemie AG in(iermany has been approved to import on the sale.The product obtains the import registration documents since 2001,and now still sold in the domestic drug market.Up to now,only two domestic enterprises to declare the preparation.including one in February 21,2017 get approval.In order to make the simethicone emulsion localization as soon as possible,this article in accordance with the "registration declaration date requirements of chemicals" in Provision for Drug Registration(CFDAQ Order No.28),the preliminary study on the formulation,analysis methods,qualiity standards and stability of the simethicone emulsion was carried out to provide the data for the registration of this product.The research contents mainly include the following parts:In the pre-preparation phase,in accordance with the standards for the registration of imported pharmaceutical products(JX20100262),China Pharmacopoeia 2015 and USP36-NF31,the simethicone emulsion(Espumisan)was studied for the physical and chemical properties,in order to determine the key quality of the simethicone emulsion properties and prepare for the follow-up experiment.On the basis of the research on the listed products,the stability and the defoaming ability of the simethicone emulsion were used as the investigation indexes to evaluate the prescription of the simethicone emulsion,determine the type and dosage of the excipients in the emulsion,the type and amount of the emulsifier.The initial optimal formulation of simethicone emulsion(100ml)was composed of 4.0g of simethicone,0.129g of Tefose 63,1.084g of polyoxyethylene(40)monstearate,25.8mg of PEG-25 stearate,0.5g of monostearate 491,0.110g of sorbic acid.6.0mg of saccharin sodium,0.5g of hydroxypropyl cellulose.0.2g of banana flavor,and purified water.Through the preparation of the prescription,the defoaming ability and centrifugal stability of the simethicone emulsion is better.The preparation process of simethicone emulsion was carried out as follows:Firstly,formulation volume of the simethicne and emulsifier were mixed uniformly at 85℃ to obtain the oil phase,part of the water-soluble excipients were added into the purified water at 85℃,stirred for dissolution to obtain an aqueous phase.Then mix up the oil phase and aqueous phase by a high-speed shear way at 5400 rpm for 10 min to obtain a primary emulsion.The remaining water was heated to 50℃,added the formulation volume of sorbic acid and saccharin sodium,stirred and dissolved,then cooled the water solution to 30℃,added formulation volume of hydroxypropyl cellulose,dissolved by stirring,after that,filtered the fluid through a 0.1 mm sieve to obtain an water phase.Finally,the primary emulsion mixed with the water phase and banana flavor by a high-speed shear at 5000rpm for 5min,filled into the appropriate container to obtain the simethicone emulsion.According to the import standards of simethicone emulsion(JX20100262),the quality standards of the simethicone emulsion in United States Pharmacopoeia 36 version.Chinese Pharmacopoeia 2015 version,and the "Technical guiding principle for the normalization process of the establishment of chemicals quality standards",the quality standards of the simethicone emulsion was formulated combined with the characteristics of the dosage form and the stability of the research results of the simethicone emulsion.A method for the determination of the relevant substances in the simethicone emulsion was established.The content of the related substances in the listed formulation Boxi and the self-made simethicone emulsion was determined.The listed product.Boxi,contained the simethicone oligomer D4 and D5.And no two of these substances in self-made simethicone emulsion,the total impurity was significantly less than the Boxi,so the quality is better than the Boxi.The self-made emulsion and the listed emulsion boxi were placed under the condition of 30 ± 2 C and 75± 5%relative humidity,the self-made emulsion was layered at 30 ± 2℃ while boxi was also layered but relatively good.The differences in sample stability were further studied by near infrared light scattering or transmission intensity map scanning through the stability analysis tester.The stability of the self-made simethicone emulsion was not as good as the listed product,and needed further study.