处方前研究.ppt

,LOGO,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,Preformulation study,Preformulation,study,Physical and Chemical,Properties,Biopharmaceutical,Properties,PharmacologicalandToxicological properties,Physical and Chemical Properties,Description of the products,Description of the business,hygrooscopicity,Solubility and Pka,Text in here,Text in here,Text in here,Text in here,Title,stability,micromeritics,hygroscopicity,Compatibility of excipient,MP and polymorphism,Text in here,Partition coefficient,solubility,Pka/Dissociation constants,drug must possess aqueous solubility for threaepeutic efficacy.,If the solubility of drug is less than desirable,consideration,must be given to improve its solubility,The extent of dissociation in many cases is highly dependent,on the Ph of the medium containing the drug,In formulation often the vehicleis adjusted to certain Ph to abtain a,certain level of ionization Or dissociation for solubility or stability,Partition coefficient,the oil-water partition coefficient(P)is a measure of a molecule lipophilic character.,Drugs which have bigger P can be easily absorbed when they have the similiar Pka value.,P=(Conc.Of drug in octanol)/(Conc.Drug in water),while octanol is the most common used,s,solvent during the measurement of the P,and,when drug exist as a monomer,P=(Conc.Of drug in octanol),n,/(Conc.Drug in water),while the drug exists as polymer,Text in here,Relation between P of barbiturates and absorption in stomach of rats,Barbiturates Pka p absorption rate(,),Barbital 7.9 0.72 6.2,Phenobarbital 7.41 4.44 12.6,Pentobarbital 8.11 24.1 17.6,Amobarbital 7.49 33.8 17.7,Polymorphic forms usually exhibit different physicochemical properties,including melting point and solubility.Evaluation of crystal structure,polymorphism,and solvate form is a very important performulation activity.The change in crystal charasteristics can influence bioavailability and chemical and physical stability and can have important implications in dosage form process functions.,Often used to determine the purity of a drug and in some cases the compatibility of various subtances before inclusion in the same dosage form,Requied dosage form,Melting Point,polymorphism,examples,polymorphism,Among different crystal types of Cimetidine,type A is the best one because of solubility,.,the dissolution rate of three types Indometacin,is increaced respectly in,phosphate buffer,By adjusting the ratio of various crystals of insulin,we can get suspension with different effective duration,During the production process,many factors can accelerate thechanges of crystal forms,such as environmental factors:humidity,water,solvent and technological factors:spraydrying,heatsterilization,freeze-drying etc.At the same time,the change in storage period also should be considered,Various techniques are used to determine the crystal properties.,polymorphism,rm,Melting Point,polymorphism,Methods used to determine crystal properties,Raman,spectroscopy,hot stage,microscopy,X-ray,diffraction,IR,SS-NMR,Thermal,analysis,methods,hygroscopicity,When solid drug absorbs moisture,it will form a liquid membrane on the surface and decomposition reaction happens.such as acetylsalicylic acid,penicillin G etc,Determine CRH of drug,preformulationly,choosing appropriate producing and storing environment,Drug who can absorbs water from surroundings has the property of hygroscopicity.The degree mainly depends on RH of environment.,、,micromeritics,stability,Mainly contains shape size particle size distribution,powderdensity adhesion mobility wettability,Useful in,prescription composition,preparation,choosing,approprate excipients etc,Compatibility of excipient,Compatibility ofsolid dosage forms,Compatibility of aqueous solution,Test method:put the mixture of drug and excipients in to a,sealedbottle,Observe if there ia any physical,change happens,then test with TLC or HPLC to,analysis content changes,Test method:mix drug with excipient solution with the,presence of,metal ion or antioxidant.the result can tell the stability,of drug and excipient in the condition of Oxidation,Illumination.,This is very important in dosage design ofinjection,Biopharmaceutical Properties,High First-passeffect,；,prodrug,b)Be metabilized with help,of enzyme,Saturation,c)Inhibit enzyme of liver:,help decreasing,metabolism of other drugs,a)Bioavailabilityspeed.,b)Degree of Bioavailability,ADME,Bioavailability,pharmacologicaland,toxicological properties,pharmacodynamics,and,pharmacology,To guide the design of drug dosage and maximize theefficacy,Toxicology,For a new drug,choosing a reasonable administration route which isbased on toxicology research is essential in dosage form design,Thank You!,