Preformulation (Part 1) PDF

PREFORMULATION (PART 1) – DR. YANG 1. What is preformulation in pharmaceutical development? A: It is the investigation of the physicochemical properties of drugs and excipients before formulation. 2. Why is preformulation important? A: It provides a foundation for developing robust formulations b...

PREFORMULATION (PART 1) – DR. YANG 1. What is preformulation in pharmaceutical development? A: It is the investigation of the physicochemical properties of drugs and excipients before formulation. 2. Why is preformulation important? A: It provides a foundation for developing robust formulations by understanding the drug’s properties. 3. What are the main goals of preformulation? A: To establish drug characteristics, necessary parameters, excipient compatibility, and stability profile. 4. When does preformulation begin in drug development? A: After a compound is synthesized and tested for pharmacological action, prior to Phase I studies. 5. What are the four primary tastes? A: Sweet, bitter, sour, and salty. 6. How is solubility defined? A: The concentration of a solute in a saturated solution at a specific temperature. 7. What does "like dissolves like" mean in solubility? A: Substances with similar polarities or intermolecular forces tend to dissolve in each other. 8. What is the heat of fusion? A: The energy required to change a solid into a liquid at its melting point. 9. What are Van der Waals forces? A: Weak intermolecular forces between non-polar molecules. 10. What are hydrogen bonds? A: Interactions between a hydrogen atom attached to an electronegative atom and another electronegative atom. 11. What are electrostatic forces? A: Forces between charged ions, calculated by Coulomb's law. 12. What are the three main classifications of solvents? A: Polar solvents, semipolar solvents, and nonpolar solvents. 13. Give an example of a polar solvent. A: Water. 14. What is the function of co-solvents in pharmaceutical formulations? A: To enhance solubility of poorly water-soluble drugs by altering the dielectric constant of the solvent system. 15. What is the solubility enhancement method using particle size reduction? A: Reducing particle size increases surface area, enhancing solubility. 16. What is the effect of pH on the solubility of weak acids? A: As pH increases, the solubility of weak acids increases. 17. What is the pH max in the context of weak acids and bases? A: It is the pH at which maximum solubility occurs for weak acids or bases. 18. What is a cosolvent system? A: A solvent mixture used to enhance drug solubility when a drug is not completely soluble in water. 19. What are the common cosolvents used in pharmaceuticals? A: Alcohol, glycerin, propylene glycol, and polyethylene glycol. 20. What is the relationship between temperature and solubility for most compounds? A: Solubility usually increases with temperature. 21. What is the exception to the usual temperature-solubility relationship? A: Calcium hydroxide shows decreased solubility with increasing temperature. 22. What is an ideal solution in the context of solubility? A: A solution where the solute-solvent interactions are similar to solute-solute and solvent- solvent interactions. 23. What is the significance of initial solubility investigations in preformulation? A: To determine the basic solubility characteristics of a drug in water, saline, HCl, or NaOH. 24. What is the role of pH adjustment in solubility enhancement? A: Adjusting the pH can increase the solubility of ionizable drugs. 25. What is the effect of adding a surfactant on solubility? A: Surfactants can improve solubility by reducing surface tension and stabilizing the drug in solution. 26. What is the importance of solubility in drug formulation? A: Solubility affects bioavailability, dissolution rate, and the overall effectiveness of the drug. 27. How does solubility relate to drug absorption? A: Drugs must be dissolved in bodily fluids to be absorbed into the bloodstream. 28. What is the dielectric constant, and how does it affect solubility in cosolvent systems? A: It is a measure of a solvent’s ability to reduce the electrostatic forces between charged particles; higher dielectric constants generally increase solubility. 29. What is the role of mole fraction in cosolvent systems? A: Mole fraction affects the dielectric constant and overall solubility of the drug in the solvent mixture. 30. What is the role of chemical modification in solubility enhancement? A: Altering the chemical structure of a drug can improve its solubility and stability. 31. What is a weak electrolyte? A: A substance that only partially ionizes in solution, affecting its solubility based on pH. 32. How can the solubility of a weak base be increased? A: By lowering the pH of the solution, which increases ionization and solubility. 33. What is the importance of solubility prediction in preformulation? A: To anticipate challenges in drug formulation and select appropriate methods for improving solubility. 34. What is the role of molar volume in solubility calculations? A: Molar volume affects how solutes interact with solvents, influencing solubility. 35. How does surface tension affect solubility? A: Higher surface tension can reduce solubility by making it harder for solute particles to disperse in the solvent. 36. What is the significance of a solubility-enhancing agent like cyclodextrin? A: Cyclodextrins can form inclusion complexes with drugs, enhancing their solubility and stability. 37. What is the role of dissolution testing in preformulation? A: To evaluate the rate at which a drug dissolves, which correlates with its bioavailability. 38. How does solubility affect drug shelf life? A: Poorly soluble drugs are more likely to precipitate out of solution, reducing their effectiveness over time. 39. What are some advanced formulation techniques to enhance solubility? A: Nanoparticle formation, solid dispersions, and liposomal formulations. 40. How does particle size reduction influence dissolution rate? A: Smaller particles dissolve more quickly due to the increased surface area. 41. What is the purpose of using oils and surfactant systems in solubility testing? A: To evaluate the solubility of hydrophobic drugs in oil-based and surfactant formulations. 42. What is the relationship between solubility and bioavailability? A: Increased solubility generally leads to improved bioavailability, as more drug is available for absorption. 43. Why is thorough preformulation work essential for NDAs (New Drug Applications)? A: It ensures that the drug’s properties are well understood, minimizing the risk of formulation failures. 44. What are the steps in initial solubility investigations? A: Testing solubility in water, saline, HCl, NaOH, and co-solvents to gather preliminary data. 45. What is the role of temperature in dissolution testing? A: Temperature influences the solubility of drugs, with most drugs dissolving faster at higher temperatures.