1、Preformulation study,Preformulation study,Physical and Chemical Properties,Biopharmaceutical Properties,Pharmacological and Toxicological properties, Physical and Chemical Properties,Description of the productsDescription of the business,hygrooscopicity,Solubility and Pka,Text in here,Text in here,T
2、ext 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 desirab
3、le,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 stabil
4、ity,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 solv
5、ent during the measurement of the P, andwhen 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,Polymorphic forms usually exhibit different physicochemical p
6、roperties ,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
7、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,polymorphism,examples,polymorphism,Among different crystal types of Cimetidine,type A is the best one b
8、ecause 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 the changes of cry
9、stal forms,such as environmental factors : humidity,water,solvent and technological factors : spray drying, heat sterilization ,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.,polymorphismrm
10、,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 acetylsali
11、cylic 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 s
12、ize particle size distribution powder density adhesion mobility wettability,Useful in prescription composition, preparation, choosingapproprate excipients etc,Compatibility of excipient,Compatibility of solid dosage forms,Compatibility of aqueous solution,Test method :put the mixture of drug and exc
13、ipients in to asealed bottleObserve if there ia any physical change happens,then test with TLC or HPLC toanalysis content changes,Test method:mix drug with excipient solution with the presence of metal ion or antioxidant.the result can tell the stabilityof drug and excipient in the condition of Oxid
14、ation, Illumination. This is very important in dosage design ofinjection, Biopharmaceutical Properties,High First-pass effect；prodrug b) Be metabilized with help of enzymeSaturation c) Inhibit enzyme of liver:help decreasing metabolism of other drugs,a)Bioavailability speed. b) Degree of Bioavailabi
15、lity,ADME,Bioavailability, pharmacological andtoxicological properties,pharmacodynamics andpharmacologyTo guide the design of drug dosage and maximize the efficacy,ToxicologyFor a new drug ,choosing a reasonable administration route which isbased on toxicology research is essential in dosage form design,Thank You !,
