Study On The Preparation Of Lifepill Containing Lisinopril And Fish Oil

Drug therapy with multiple ingredients is widely accepted nowadays for treatment of cardiovascular diseases. However, for treatment of chronic conditions, taking multiple pills each time could be a daunting task especially for senior citizens. An integrated dosage form containing all the functioning ingredients may be a good solution. The well used cardiovascular drugs and supplements include lisinopril, lovastatin, atenolol, aspirin, folic acid and fish oil. While fish oil is an important supplement for maintaining cardiovascular conditions, incorporating liquid fish oil of large volume into a single formulation together with solid ingredients is a technical challenge (because physical contact between solid and liquid is much more intimate than that between solid and solid).The present study is aimed to develop an integrated pill in which solid ingredients can be mixed with fish oil without drug-drug interaction, especially between solid ingredients and liquid oil. To establish the proof-of-concept, lisinopril was selected as a model drug to be mixed with fish oil and examined. In order to avoid lisinopril-fish oil contact, the solid drug was microencapsulated in polyvinyl alcohol microspheres (abbreviated as LIS-PVA-MS) prior to suspending into fish oil, followed by fabricating soft gel capsules. (the approach to microencapsulate fish oil into solid particles for tableting was ruled out for its large dose volume).LIS-PVA-MS were prepared via two procedures, water-in-oil emulsification, followed by a freeze-thaw process and spray-drying. The former produces particles with dense matrix, but the process is lengthy with low drug loading efficiency. The later is more doable while particles possess some pore structures. Due to the good doability, we focused on the spray-drying method and optimized formulation parameters as PVA molecular weight, PVA concentration, LIS/PVA ratio, and rotation speed of the spray atomizer.According to the optimized parameters, LIS-PVA-MS with mean diameter of 17.29 um, span of 0.88, drug loading of 31.4% and encapsulation efficiency of 94.20 % were prepared. When the these microspheres were subjected to in vitro dissolution tests, 90% of the LIS-loads were released within 30min.A preliminary stability study of Lifepill containing LIS-PVA-MS and fish oil at room temperature, 40℃and 60℃, evaluated by appearance and remained LIS, indicates that the PVA protection improved LIS stability when the LIS-PVA-MS were suspended in fish oil under a nitrogen atmosphere as compared with bare LIS particles suspended in fish oil.Conclusion: Lisinopril protected in LIS-PVA-MS prepared by spray-drying exhibited significantly improved stability in fish oil and immediate dissolution profile. The HPLC method to determine lisinopril content in microspheres is simple, fast and reliable. Nitrogen atmosphere used to feel porous LIS-PVA-MS into capsules also improved drug stability.