Physicochemical properties Biopharmaceutics and Pharmacokinetics by Vishnu Datta M

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Physicochemical properties Biopharmaceutics and Pharmacokinetics by Vishnu Datta M

  1. 1. Physicochemical properties of drug substances. - Vishnu Datta.M
  2. 2. Physicochemical properties of drug substances • • • • • • • • • Drug solubility and dissolution rate Particle size and effective surface area Polymorphism and Amorphism Pseudo polymorphism (hydrates/solvates) Drug stability Salt form of the drug Lipophilicity of the drug pka of the drug and gastrointestinal pH Stereochemical nature of the drug
  3. 3. Particle size & Effective surface area
  4. 4. Particle size & Effective surface area • Particle size and surface area of a solid drug are inversely related. • Two types of surface area of interest are:  Absolute surface area  Effective surface area
  5. 5. Particle size & Effective surface area • Absolute surface area which is the total area of solid surface of any particle. • Effective surface area which is the area of solid surface exposed to the dissolution medium.
  6. 6. Particle size & Effective surface area
  7. 7. Particle size & Effective surface area • Micronisation>>>reduction of particle size • Surface of such small particles has higher energy than the bulk of the solid >>>increased interaction with the solvent
  8. 8. Particle size & Effective surface area • In case of non hydrophobic drugs(griseofulvin, chloramphenicol, salts of tetracycline) >>>micronisation>>>superior dissolution rate in comparison to the simple milled form of these drugs. >>>decreased dose >>>increased absorption efficiency • Ex: Griseofulvin reduced to half and Spironolactone decreased 20 times
  9. 9. Particle size & Effective surface area • In case of hydrophobic drugs (aspirin, phenacetin, phenobarbital)>>>decrease in effective surface area of such powders>>>fall in the dissolution rate.
  10. 10. Reasons suggested for the outcome • The hydrophobic surface of the drug adsorbs air onto their surface which inhibits wettability. • The particles re-aggregate to form larger particles due to their high surface free energy which either float on the surface or settle at the bottom of dissolution medium
  11. 11. Overcome the effects to increase the effective surface area • Use of surfactant as a wetting agent Decreases the interfacial tension Displaces the adsorbed air with the solvent Ex: polysorbate 80 increases the bioavailability of phenacetin by promoting wettability • Adding hydrophilic diluents such as PEG, PVP, Dextrose etc which coat the surface of hydrophobic drug particles and render them hydrophilic. …
  12. 12. Physicochemical properties of drug substances • • • • • • • • • Drug solubility and dissolution rate Particle size and effective surface area Polymorphism and Amorphism Pseudo polymorphism (hydrates/solvates) Drug stability Salt form of the drug Lipophilicity of the drug pka of the drug and gastrointestinal pH Stereochemical nature of the drug
  13. 13. Polymorphism • Depending on the internal structure a solid can exist either in a crystalline or amorphous. • When a substance exists in more than one crystalline form, the different forms are designated as polymorphs and the phenomenon as polymorphism .
  14. 14. Polymorphism • Polymorphs are two types Enantiotropic polymorph is the one which can be reversibly changed into another form by altering the temperature or pressure.ex:sulphur Monotropic polymorph is the one which is unstable at all temperatures and pressures eg:glyceryl stearates.
  15. 15. Polymorphism • Polymorphs differs in physical properties >>> solubility, Melting point, density, hardness and compression characteristics • The existence of the polymorphs can be determined by using techniques like>>>optical crystallography, x-ray diffraction, differential scanning calorimetry etc.
  16. 16. Polymorphism • Among the polymorphic forms>>>stable form>>>lowest energy>>>highest melting point>>>least aqueous solubility • Remaining polymorphs are called metastable forms which represent>>>higher energy state>>>lower melting point>>>higher aqueous solubility
  17. 17. Polymorphism • As the metastable forms have greater solubility they show better availability and are preferred in formulation • Ex chloramphenicol palmitate A,B,C,D B shows best bioavailability A is virtually inactive biologically
  18. 18. Amorphous form • Drugs also exist as amorphous form >>>have greater aqueous solubility than the crystalline forms>>>energy required to transfer a molecule from lattice is greater than that required for amorphous • Ex: cortisone acetate is 3 times more soluble than crystalline form • Order of dissolution is Amorphous>metastable>stable
  19. 19. Physicochemical properties of drug substances • • • • • • • • • Drug solubility and dissolution rate Particle size and effective surface area Polymorphism and Amorphism Pseudo polymorphism (hydrates/solvates) Drug stability Salt form of the drug Lipophilicity of the drug pka of the drug and gastrointestinal pH Stereochemical nature of the drug
  20. 20. Pseudopolymorphism  When the solvent molecules are incorporated in the crystal lattice of the solid are called as the solvates  The solvates can exist in different crystalline form called as pseudopolymorphs. The phenomenon is called pseudopolymorphism.
  21. 21. Hydrates and Solvates • If case Entrapped Solvent is water then it is referred as Hydrate. • Anhydrous form of the drug has greater aqueous solubility then the hydrates. (because already in interaction with water have less energy for crystal break up in comparison to the anhydrates). • Solvates differ in their physical parameters.
  22. 22. Physicochemical properties of drug substances • • • • • • • • • Drug solubility and dissolution rate Particle size and effective surface area Polymorphism and Amorphism Pseudo polymorphism (hydrates/solvates) Drug stability Salt form of the drug Lipophilicity of the drug pka of the drug and gastrointestinal pH Stereochemical nature of the drug
  23. 23. Drug stability • A drug for oral use may destabilize either during its shelf-life or in the GIT • Major stability problems resulting in poor bioavailability of an orally administered drug Degradation of drug into inactive form Interaction with one or more different component(s) to form a complex that is poorly soluble or is unabsorbable
  24. 24. ~~REFERENCES~~ • Physical pharmacy, fourth edition, Alfred martin. • Pharmaceutics The science of dosage form design 2nd edition- M.E Aulton • Dissolution, Bioavailability & Bioequivalence Hamed M.Abdou • Brahmankar D.M., Biopharmaceutics & pharmacokinetics A Treatise • Biopharmaceutics and clinical pharmacokinetics an introducion fourth edition Robert E.Notari
  25. 25. ~~THANK YOU~~ • Knowledge of what is does not open the door directly to what should be………. » Albert Einstein

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