| Children with attention deficit hyperactivity disorder?ADHD?is a common childhood mental disorders,the main symptoms of the disease are: attention disorders,impulsive behavior,and hyperactivity easily distracted,often accompanied by learning difficulties and conduct disorder.The survey found that the prevalence of domestic groups of children at 1.5-10%,due to the lack of sufficient attention to the long-term disease and a higher incidence of actual disease.Comprehensive treatment of ADHD,including long-term drug therapy and psychological intervention.Methylphenidate hydrochloride(chemical name: ?-a phenyl-2-piperidine acetate hydrochloride,molecular formula: C14H19NO2 ? HCI,MW: 269.77)is the first-line drug treatment for ADHD,it is soluble in water and alcohol,rapid onset of effect after administration,at present,there are two formulations of oral and injectable clinically.Injection doses of 1 can be maintained for about 4 h,rapidly metabolized in vivo half-life?T1 / 2?= 30 min,excreted by the kidneys.More use of immediate release methylphenidate hydrochloride tablets?IR2MPH,Ritalin?.The drug is rapidly absorbed orally,about 2h after administration,which amounts to maximum plasma concentration,sustainable 1 4 h,but prone to break-even after the effect?the concentration of drug in the body in the morning medication begins to decrease,the attention deficit in the morning half of the course may increase?,peak plasma concentration fluctuations.Immediate release tablets twice a day or three times a medication,which missed a higher rate,efficiency poorer children go home at night doing homework,parents of children at home,failed to see the change.US ALZA company developed methylphenidate hydrochloride controlled release tablets?trade name: focus up,Concerta?,is taken once daily controllability of methylphenidate drugs,it is a three-osmotic pump capsule-shaped tablets,the preparation process more complex,the need to prepare two different drug content of the drug-containing layer of particles and particle content were measured,and then the tablet,a long preparation period,the heavy workload.The main accessories die poor thermal stability.Tablet is too large,it is difficult to take.To solve these problems,the subject of the use of advanced OROS osmotic pump prepared biphasic release type layer osmotic pump tablets,taken once daily,namely sustainable 12 h efficacy.The bilayer film production process is simple,low cost die materials,and expand production.The osmotic pump tablets with osmotic controlled release rate,based on in vitro release test results,the cumulative release concentrations rose rapidly in the early stages,1 2 h after reaching a local maximum value,6 8 h to reach peak concentration;early showed an increasing release drugs,post kept constant.Layer osmotic pump preparation by the drug-containing layer,the push layer and semipermeable membrane coating layer composed of a solid preparation,it was a zero-order release of the drug,compared with other dosage forms has the following advantages: 1 constant speed release it in the body drugs,the maximum to avoid the peak plasma concentration after taking the phenomenon caused by effectively reducing the side effects of drugs;2 after entering the body can release a constant speed in a certain time,but not the stomach and intestines,the media environment and other physiological factors affect the body;3 medication convenient,reducing the number of administrations,can significantly improve patient compliance,to play the formulation efficacy and safety features;4 osmotic pump formulation development cycle is short,high-tech,easy-to-industry technology;5 osmotic pump formulation film coating can mask the bad odor of drugs.Therefore,this study is intended to be used as the main drug methylphenidate hydrochloride,using osmotic pump technology slow-release drug delivery systems and biphasic,biphasic methylphenidate hydrochloride controlled release preparation osmotic pump tablets.By film-coating in the outer layer of immediate release tablets packet layer coating film,the tablet can rise rapidly in the early release of the in vitro release behavior of the drug to achieve the results and immediate treatment.By methylphenidate hydrochloride controlled release osmotic pump tablets biphasic preparation and formulation optimization,stability studies,the optimal formulation and preparation process,to achieve optimal clinical efficacy.1 Quality Control duplex controlled-release methylphenidate hydrochloride osmotic pump tabletsTo control the quality of methylphenidate hydrochloride biphasic controlled release osmotic pump tablets,the paper according to the characteristics of the formulation,using high performance liquid chromatography?HPLC?,established for the determination of methylphenidate hydrochloride indicators methylphenidate hydrochloride duplex control the method of determination and the determination of the release of release osmotic pump tablets.Wherein the determination of chromatographic conditions: Column: Diamonsil C18?250mm × 4.6mm,5?m?,the mobile phase was 0.02 mol·L-1 potassium dihydrogen phosphate solution?with 1% phosphoric acid solution adjusted to pH 3.0?: acetonitrile = 70:30,detection wavelength of 220 nm,the flow rate was 1.0 m L·min-1,the column temperature was 35 ?,the injection volume of 20ul;the results show that under the above chromatographic conditions,the concentration of methylphenidate hydrochloride in 1.0 24.0?g· mL-1 good linear relationship,r = 0.9995,the average recovery was 100.5%,RSD was 1.58%?n = 6?.Description HPLC method for the determination of specific and established a good,fast and sensitive,accurate and can be used to determine the content of a two-phase controlled-release methylphenidate hydrochloride osmotic pump tablets.Release experiments in accordance with the "Chinese Pharmacopoeia" 2010 edition of Appendix XC second dissolution test method to pH3.0 phosphate buffer solution 900 ml for the release of medium speed of 50 revolutions per minute,medium temperature?37 ± 0.5?? It was taken liquid 4ml,0.45?m filter membrane in 0.5,1,2,3,4,6,8,10 hour,depicting 2mL filtrate as the test solution,and immediately added the same temperature,the same volume of release medium,measured at chromatographic conditions.The results showed that the concentration of methylphenidate hydrochloride 1.0 24.0?g·mL-1 good linear relationship,r = 0.9995,the average recovery was 100.5%,RSD was 1.58%?n=6?.Illustrate the determination of methylphenidate hydrochloride controlled release biphasic permeation HPLC pump tablets specificity in vitro release of well established,fast and sensitive,can be used as methylphenidate hydrochloride controlled release osmotic pump tablets biphasic release determination.Determination method and dissolution testing method established in this study can be accurate and sensitive determination of methylphenidate hydrochloride biphasic controlled release osmotic pump tablets of the drug content of the cumulative release within 10 hours and to establish quality control standards to provide basis.2 Study on Preparation duplex controlled-release methylphenidate hydrochloride osmotic pump tabletsThis selection of sodium chloride?Na Cl?and polymer materials of different molecular weight poly?ethylene oxide??PEO?as the main material of the die,which is the active substance and osmotic pressure boosting materials,with polyethylene glycol?4000?and cellulose acetate?CA?for the coating material,an organic coating solvent acetone in a double layer tablet core outsourcing cellulose acetate semipermeable membrane coating weight to a predetermined weight,remove,set 40 ? dried 24 h,with laser hole machine on white playing a hole diameter of 0.7mm release drug-containing layer side.Take prescription of methylphenidate hydrochloride,dissolved in an appropriate amount of water and slowly adding a certain amount of Opadry 200,stir,made immediate release film coating liquid layer,double-layer film-coated tablets,to a weight gain after passing,dried 24 h at 40? to remove residual solvent,which obtained biphasic methylphenidate hydrochloride controlled release osmotic pump tablets.According to the release mechanism osmotic pump formulations,using FDA recommended f2 similarity factor as an in vitro release evaluation,mainly from the drug-containing layer prescription,prescription push layer,coating film prescription,preparation and controlled release tablets in vitro release studied medicine conditions five levels.By single factor,select the content?factor A?drug-containing layer of sodium chloride,poly push layer oxygen content?factor B?of ethylene,the coating film weight gain?factor C?of three factors as independent variables,piperazine hydrochlo ride methyl biphasic controlled release osmotic pump tablets 12 h drugs in vitro cumulative release rate?Q?as the dependent variable,optimized formulation of methylphenidate hydrochloride obtained biphasic controlled release osmotic pump tablets in vitro release curve 2-10 hours in line zero-order release,good reproducibility.3 Stability duplex controlled-release methylphenidate hydrochloride osmotic pump tablets According to "Chinese Pharmacopoeia" drug stability and the guiding principles of methylphenidate hydrochloride controlled release osmotic pump tablets duplex quality control standards,the paper duplex controlled-release methylphenidate hydrochloride osmotic pump tablets a preliminary stability study,each comprising Stress testing,accelerated testing and long-term tests.?1?test factors: high temperature test,the test will be placed on the surface of the dish,placed in 60 ? constant temperature oven at 10 days,respectively,in the first 0,5,10 day samples,measured in accordance with the test method to check the results of each inspection indicators They are stable,no significant change.Humidity test,the test will be placed in a sealed container in a constant temperature and relative humidity?RH?92.5%,for 10 days at a temperature of 25 ?,respectively,in the first 0,5,10 day samples observed measured,the results showed the drug hole out from release,therefore,the product should be kept in closed,dry environment.Bright light test,the test will be placed for 10 days under illumination 4500 Lx illumination,0,5,10,respectively,on the first day of sampling according to the determination,the test results show that bright light drugs without significant changes.?2?acceleration test,the self-made duplex controlled-release methylphenidate hydrochloride osmotic pump tablets three batches of samples were placed in an aluminum aluminum packaging,at 40 ? ± 2 ?,relative humidity of 75% ± 5% under the condition for 6 months,respectively,in the first months of 0,1,3,6 sampling carried out the inspection measurement,the test results of three batches of samples were no significant changes in all the indexes were within normal range.?3?long-term test,the homemade biphasic methylphenidate hydrochloride controlled release osmotic pump tablets within three batches of samples were placed in an aluminum aluminum packaging,at 25 ? ± 2 ?,relative humidity 60% ± 10% of the conditions placed at its 0,1,3,6 months sampling carried out the inspection measurement results showed that all the indexes were within the normal range,no significant change.Thus,the two-phase controlled-release methylphenidate hydrochloride osmotic pump tablets on high-humidity... |
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