Hubungan Salting Out, Salting in, Klatrat, Solid in Solid Solution Dengan Absorpsi-Disolusi

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Transcript of Hubungan Salting Out, Salting in, Klatrat, Solid in Solid Solution Dengan Absorpsi-Disolusi

Hubungan Salting Out, Salting In, Klatrat, Solid in Solid Solution dengan Absorpsi/ Disolusi

Relationship Between Formation of Complexes & Prodrugs and Absorption/DissolutionSukamto S MVarious Methods to Enhance Drug SolubilityPhysical modifications

Particle size reduction Modification of the crystal habits Drugs dispersion in carriers Solubilization by surfactantsChemical modifications

Complexations Soluble pro-drugs Salt formationsOther techniques

Co-crystallization Co-solvency Solubilizing agents Nanotechnology approachCOMPLEXATIONComplexationComplex (coordinated compound) is ...

ComplexationComplexation of a drug may occur:Within the dosage formIn the gastrointestinal fluidComplexation has two effects on absorption:It can be beneficial (increase solubility)Cyclodextrin & itraconazoleIt can be detrimental (decrease solubility)Tetracyclines & calcium

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Complex is also found within the plasma such as in heme B as cofactor of hemoglobin. Complex formed between beta-lactam antibiotics and metal ions, such as Cu2+, will decrease duration of the antibiotics.

How Complex can Increase Drug Solubility? Cyclodextrins

How Complex can Increase Drug Solubility? Cyclodextrins

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Of those three types of cyclodextrin, the most used is -cyclodextrins. However, it is contraindicated for parenteral dosage form. In this case, the formulators use the derivates of -cyclodextrins.How Complex can Increase Drug Solubility? Cyclodextrins

How Complex can Increase Drug Solubility? Cyclodextrins

Cyclodextrins-Complexed DrugsMiconazoleIt has poor solubilityAfter being complexed with cyclodextrin, the solubility increases up to 55-fold and dissolution rate goes up to 255-fold.PGE2 (Prostarmon)Piroxicam (Brexin)Itraconazole (Sporanox)AripiprazoleOmeprazoleDexamethasoneHighlight..!!!

Before being complexed with cyclodextrin, ITRACONAZOLEs solubility is about 1 ng/mL. After being complexed with cyclodextrin, the solubility increases to 10 mg/mL.ClathratesIt is a cage-like lattice of one type of molecules entraps a second type of molecules.

ClathratesSeveral compounds can form clathrates.Gallic acidUreaThioureaZeolith The guest molecules which can be trapped in the cage formed by the compounds above.CholesterolVitamin ALinoleic and linolenic acid

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Methane clathrate is associated with the source of energy and can cause tsunami.

PRODRUG APPROACHProdrugsAn ideal prodrug is a chemical entity that has no pharmacological activity against a designated physiological target, but is metabolically transformed into a compound with the desired activityProdrugs can be used: To improve drug delivery or pharmacokinetics (solubilicity & lipophilicity)To change properties of the drugsTo decrease toxicityTo target the drug to specific cells or tissuesHighlight..!!!

Codeine MorphineLipophilicity Vs SolubilityAn increase in lipophilicity is usually accompanied by a decrease in water solubility

Prodrugs to Increase SolubilityIntroduction of an ionizable functional group allowing various salts of such prodrugs to be formed.Phosphate esters Prednisolone phosphateAmino acid esters ValacyclovirHemiesters of dicarboxylic acids, Chloramphenicol sodium succinateDisruption of the crystal lattice VidarabineHighlight..!!!

Salting-In Addition of salt will INCREASE solubility of the compound. Salting-Out Addition of salt will DECREASE solubility of the compoundProdrugs to Increase LipophilicityMany prodrugs feature the addition of a hydrophobic group in order to increase their lipid solubility to improve their gastrointestinal absorption.BacampicillinPivampicillinTalampicillinSeveral drugs is formed into prodrug to enhance the affinity to carrier/transporter so that it can increase the absorption.ACE Inhibitors, except Captopril and LisinoprilAmpicillin

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