Study On The Pyrithione Hydrochloride Osmotic Pump Tablet

ObjectivePyrithione hydrochloride is one of the most commonly used drugs for the clinical treatment of Alzheimer’s disease.At present,China’s listed pyritinol preparations include injections,ordinary tablets and capsules.Injection is not convenient,and has serious irritations on blood vessels.The excessive number of daily doses of capsules and ordinary tablets leads to large fluctuations in the peak-to-valley concentration of blood,which results in low patient compliance and side effects.The advantages of the osmotic pump formulation are that it can reduce the number of medications and reduce the plasma concentration of the drug in the body,enabling zero-level drug release and longer controlled release time,thereby increasing patient compliance and reducing drug side effects.Based on the above reasons,this article selected pyritinol hydrochloride as a model drug,and then prepared pyrithione hydrochloride osmotic pump tablets to improve the safety and patient compliance of pyrithiol hydrochloride preparations.MethodsIn this paper,this article selected pyritinol hydrochloride as a model drug,microcrystalline cellulose as a filler,glucose as a penetration enhancer,magnesium stearate as a lubricant,polyvinylpyrrolidone K30 as a binder to prepare tablets by wet granulation;cellulose acetate as coating material,polyethylene glycol 4000 as porogen and acetone as coating liquid solvent to prepare coating liquid.Subsequently,the tablet core was coated toprepare an osmotic pump sheet.Single factor study and star point design-response surface optimization prescription,one HPLC method for the determination of pyrithiol hydrochloride was established.The self-made pyrimidine hydrochloride osmotic pump tablets were used as test preparations,and commercially available pyrithithiol hydrochloride tablets were used as reference preparations.We measured blood concentration at different time points and drawn blood concentration-time curve to calculate the relevant pharmacokinetic parameters by using six rabbits through two formulations,double-cycle single-dose oral administration experiment.ResultsThe optimum formulation was determined to be pyritinol hydrochloride 150 mg,glucose 6.31 mg,polyvinylpyrrolidone K30 16 mg,microcrystalline cellulose27.69 mg,polyethylene glycol 4000 2.1 mg,coating weight gain 3.85% by using the in vitro cumulative release as evaluation index,f2 similarity factor to determine the similarity of drug release curve,the single factor experiment and the star design-response surface metheod.Optimized pyrithione hydrochloride osmotic pump release equation is:Q=7.936 t+0.648(r=0.997),in line with zero-level release.And the release behavior in vitro was not affected by release conditions and other factors.The results of pharmacokinetic experiments in rabbits showed that the relative bioavailability was significantly improved and the main pharmacokinetic parameters of the tested preparations were:Cmax(3.71±0.64)μg·m L-1,(6.19±1.96)μg·m L-1;Tmax(6.67±0.94)h,(3.33±0.47)h;AUC0~t(30.25±2.14)μg·h·m L-1,(19.74±2.76)μg·h·m L-1;AUC0~∞(31.16±3.54)μg·h·m L-1,(19.91±2.39)μg·h·m L-1.ConclusionsThe homemade pyrithione hydrochloride osmotic pump tablet has a reasonable prescription,high process feasibility,obvious controlled release characteristics,and good reproducibility.In vivo pharmacokinetic experimentsshowed that,compared with conventional tablets,the pyrithiol hydrochloride osmotic pump tablets showed lower peak concentration,longer peak time,and significantly improved bioavailability.The objective of the experiment was achieved.It provides an effective reference for the clinical application of pyridoxine hydrochloride.