polymorph.pptx
- 1. Physical Pharmacy crystal structure and solubility 1 collection by ph/Aref alshmiry
- 2. Factors affecting solubility of drug 1. Solute related, 2. Solvent related, 3. Environment related, 4. Formulation related. 2
- 3. Solute related 3 1 - Structural features of drug(e.g polar and nonpolar), 2 - Nature of drug (e.g particle size, surface area and shape), 3 - Physicochemical properties of drug(e.g melting and boiling point), 4 - Physical form of drug(e.g amorphous and crystalline).
- 4. Solvent related - Nature of solvent, - PH of solvent, - Volume of solvent. 4
- 5. Environment related - Temperature, - Pressure. 5
- 6. Formulation related - Common ion effect, - Effect of indifferent electrolyte, - Effect of nonelectrolyte on solubility of electrolyte, - Effect of electrolyte on solubility of non-electrolyte, - Effect of complex formation, - Effect of surface active agent. 6
- 7. Solids and the crystalline state A crystalline solid defined as a substance (clear and bright like crystal) possesses rigid and long-range order. In a crystalline solid, atoms, molecules or ions occupy specific (predicable) positions. An amorphous solid defined as a substance does not possess a will-defined arrangement and long-range molecular order. 7
- 8. 8 Solids and the crystalline state
- 9. 9 Solids and the crystalline state
- 10. 10 Solids and the crystalline state
- 11. 11 Solids and the crystalline state
- 12. 12 Solids and the crystalline state The seven possible primitive unit cells
- 13. 13 Solids and the crystalline state
- 14. 14 Solids and the crystalline state
- 15. 15 Solids and the crystalline state Caesium chloride Zinc sulfide Calcium fluoride
- 16. 16 Solids and the crystalline state Molecular crystals: • Lattice points occupied by molecules. • held together by weak attraction forces. • soft, low melting point. • bad conductors of heat and electricity. • Common examples include wax, iodine and Sulphur. wax
- 17. 17 Solids and the crystalline state
- 18. 18 Solids and the crystalline state
- 19. 19 Solids and the crystalline state
- 20. 20 polymorphism Some elemental substance such as Carbon and Sulfur, may exist in more than one crystalline form and are called allotropic, which is a special case of polymorphism. Polymorphism is the ability of a substance to exist in more than one crystal structure
- 21. 21 polymorphism Polymorphs: when two crystals have the same chemical composition but different internal structure (molecular packing – molecular conformation or / and inter or intra molecular interactions) modifications or polymorphs or forms Pseudo polymorphs: different crystal forms have molecules of the same given substances and also contain molecules of solvent incorporated into a unique structure (solvates or hydrates (water))
- 22. 22 polymorph
- 23. 23 polymorph
- 24. 24 Pharmaceutical synthesis include purification and crystallization, residual solvent can be trapped in the lattice. (this result in the formation of cocrystal or solvate.) The presence of residual solvent may affect dramatically the crystalline structure of the solid depending on the type and/or inter molecular forces that the solvent may have with crystalline solid. Solvates
- 25. 25 Cocrystal The simplest definition of a cocrystal is a crystalline structure made up of two or more components in a definite stoichiometric ration, where each component is defined as either an atom, ion, or molecule.
- 26. 26 When the change from one form to another is reversible, it is called enantiotropic. When the transition takes place in one direction only--for example, from a metastable to a stable form –the change is called monotropic. Principle of polymorphism
- 27. 27 Amorphous solid An amorphous solid does not possess a well-defined arrangement and long-range molecular order. Amorphous substances, as well as cubic crystal and isotropic, that is exhibit similar properties in all direction.
- 28. 28 Amorphous solid Solids that don’t have a definite geometrical shape are known as amorphous solids. 1. In these solids particles are randomly arranged in three dimension. 2. They don’t have sharp melting points. 3. Amorphous solids are formed due to sudden cooling of liquid. 4. Amorphous solids melt over a wide range of temperature.
- 29. Differences between crystalline and amorphous form Crystalline forms Fixed internal structure, More stable than its amorphous form, Lesser solubility than its amorphous form, Lesser tendency to change its form during storage. Amorphous forms Do not have any fixed internal structure, Higher thermodynamic energy than its crystalline form,(less stable) Greater solubility than its crystalline form, Tend to change its form during storage. 29
- 30. 30 Polymorphism and Industry / Pharmaceutical API Crystallization Filtration Drying Milling Bulk API Final form Granulation Drying Milling Tableting/compaction Drug product Solubility
- 31. 31 Crystallization General crystallization conditions:- The formation of polymorphs crystallization process, depend upon Solvents—different polarities (the packing of a crystal may be different from a polar versus a nonpolar solvent), Concentration of the solutions (super saturated, saturated, diluted) (generally the higher the concentration above the solubility, the more chance a metastable form is seen), Cooling speed (quenching, slow), Temperature (room or lower than room temperature), Impurities that may favor a metastable polymorph because of specific inhibition of growth patterns.
- 32. 5/12/2023 32 Melting point . Hardness. Optical, electrical magnetic properties. Color. IR spectra. NMR spectra. Photochemical reactivity. Thermal analysis. Dissolution rate Bioavailability Physical and chemical stability Solubility and melting point are very important in pharmaceutical processes including dissolution and formulation. Polymorphism and Industry / Pharmaceutical
- 33. 33 Polymorphism and industry/pharmaceutical In the case of slightly soluble drugs, this may affect the rate of dissolution. As a result, one polymorph may be more active therapeutically than another of the same drug. the polymorphic state of chloramphenicol palmitate has a significant influence on the biologic availability of the drug.
- 35. 35 Amorphous or crystalline & therapeutic activity The crystalline form of the antibiotic novobiocin acid is poorly absorbed and has no activity, where the amorphous form is readily absorbed and therapeutically active, due to different dissolution rate.
- 37. 37 Formulation problems Polymorphism with certain crystal habits may be difficult to inject in suspension form or to formulate as tablets, Transformation between polymorphic form during storage can cause changes in crystal size in suspensions and their eventual caking, Crystal growth in cream as result of phase transformation can cause the cream to become gritty, Changes in polymorphism form of vehicles such as Theobroma oil, used to make suppositories could cause products with different and unacceptable melting characteristics. Polymorphism and industry/pharmaceutical