Study On The Optimization Of The Formulation Of Ibuprofen Sustained Release Capsules

Ibuprofen is a safe and efficient propionicacid Nonsteroidal antiinflamma tory drugs(NSAIDs), which is widely used in the treatment of fev er, pai nandinflammation. Because ofeliminating soon in the body (serous half-life is 1.8h to 2h), the drug is taken three times a day to maintain the treatment concentration in body. In general, the Nonsteroidal antiinflammatory drugs(NSAIDs) are easy to cause gastrointestinal ulceration and anorexia when given in an oral formulation, but the sustained-release preparation can reduce the side effect of the gastrointestinal tract and improve the clinical effects. The sustained-release preparation have been developed abroad since 1980s, Ibuprofen Sustained Release Capsules is originally developed by China Tianjin SmithKline Pharmaceutical Co. Ltd. (GSK). At present, theIbuprofen sustained release preparations mainly includematrixtablets, coated pellets capsules, microsphere, liposomes, etc.The Ibuprofen Sustained Release Capsules manufactured by our company is obtained approval for production in 2006, batch production have been conducted for the product at present, and the product had been contained in Chinese pharmacopoeia of 2010 edition. For the manufacturing process, pellets is prepared with the pan-coating method, then is filled in capsules. The prescription composition are medicinalmicro pellet core (Sugar spheres), stearic acid, polyvinypyrrolidone K30The Ibuprofen Sustained Release Capsules have been manufactured by our company for many years, however conglutination is found between the pellets in the capsule in the expiry date, the serious situation is sticking together in a mass which may cause the release unqualified. It has a serious impact on the product quality and the growth of the market.The study is to screen the bestfilm coating through orthogonal design, the film coating with moistureproof function is added on the basis of original production prescription and original manufacturing process, the film coating materials for study includes hydroxypropylmethyl cellulose (HPMC), stearic acid, arosil, etc. with different percentage and different viscosity. Determine the in vitro release and evaluate the release characteristics for improving current situation and improving the stability of product through.In the study, the pellet core of Ibuprofen Sustained Release Capsules is prepared with original manufacturing process, the effect on in vitro release characteristics and moistureproof function of the product are investigated with different viscosity of hydroxypropyl methyl cellulose (HPMC), different quantity of stearic acid and different kind oflubricant. The assay of Ibuprofen in the Ibuprofen Sustained Release Capsules is determined by HPLC method. Adoptingorthogonal design, theaccumulating release in vitro, anti-sticking property and moisture absorptionproperty of the pellets prepared with different prescriptionare investigated on the time of 1h,2h,4h,7h. The best prescription is designed according to the testing data. Carry out the test under the condition of release medium (to 68.05g of monopotassium phosphate add 56mL of lmol/Lsodium hydroxide solution, dilute to 1000mL with water, mix well, the pH should be 6.0±0.05) and the rotate speed (30r/min). the best prescription of moistureprooffilm coating is obtained, that is 0.2% stearic acid as plasticizer,3% HPMCK4M which is aqueous film-forming materials,2% aerosol as lubricant, the coating material temperature is 60 ℃. When the pellet is prepared with the best prescription and the manufacturing process, theconglutination of pellets is better to improve and the in vitro release comply with that of quality standard of Ibuprofen Sustained Release Capsules contained in part Ⅱ of Chinese pharmacopoeia of 2010 edition.After the preparation process is completed, carry out the consistency of the evaluation in vitro between the prepared product and the original drug,5 release curves are respectively determined under the condition of water, pHl,2 hydrochloride acid, pH5.5 buffer solution, pH6.0 buffer solution and pH 6.8 buffer solution, the f2 value is calculated and all are over 50.The testing results show that the Ibuprofen Sustained Release Capsules prepared with the pellets which are added film coating with stearic acid, HPMCK4M and aerosol, can assure that the in vitro release meet the requirement of quality standard and can prevent the conglutination between the pellets, and the in vitro release is consistent with that of the original drug.