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Questions and Answers
What term is used for substances that exist in more than one crystalline form?
What term is used for substances that exist in more than one crystalline form?
Amorphous forms have a well-defined molecular structure.
Amorphous forms have a well-defined molecular structure.
False (B)
List two physical properties that differ between polymorphs.
List two physical properties that differ between polymorphs.
Melting point, Solubility
Polymorphs with high melting points generally have _____ solubility.
Polymorphs with high melting points generally have _____ solubility.
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Match the following characteristics with their respective types:
Match the following characteristics with their respective types:
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Which of the following statements is true regarding surfactants?
Which of the following statements is true regarding surfactants?
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Increasing boiling and melting points generally leads to increased aqueous solubility.
Increasing boiling and melting points generally leads to increased aqueous solubility.
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How does molecular size affect the solubility of a substance?
How does molecular size affect the solubility of a substance?
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What temperature is distilled water maintained at for parenteral use to ensure dissolved gases are minimized?
What temperature is distilled water maintained at for parenteral use to ensure dissolved gases are minimized?
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Dissolved air has no effect on the boiling of liquids.
Dissolved air has no effect on the boiling of liquids.
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What law describes the relationship between partial pressures of components in a liquid solution?
What law describes the relationship between partial pressures of components in a liquid solution?
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An example of a hydroalcoholic solution is formed by mixing alcohol with ______.
An example of a hydroalcoholic solution is formed by mixing alcohol with ______.
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Match the following types of solutions with their characteristics:
Match the following types of solutions with their characteristics:
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Which of the following statements best describes an ideal solution?
Which of the following statements best describes an ideal solution?
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Mixtures of benzene and ethylene chloride exhibit real solution behavior.
Mixtures of benzene and ethylene chloride exhibit real solution behavior.
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The partial pressure of each component in a solution is equal to the mole fraction multiplied by the ______ pressure of the pure component.
The partial pressure of each component in a solution is equal to the mole fraction multiplied by the ______ pressure of the pure component.
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Which functional group is associated with hydrophilic characteristics?
Which functional group is associated with hydrophilic characteristics?
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Cyclodextrins can enhance the solubility of poorly soluble drugs.
Cyclodextrins can enhance the solubility of poorly soluble drugs.
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The ___________ group contributes to the lipophilic nature of molecules.
The ___________ group contributes to the lipophilic nature of molecules.
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What is the phenomenon called when the solubility of a substance is enhanced by the addition of water miscible solvents?
What is the phenomenon called when the solubility of a substance is enhanced by the addition of water miscible solvents?
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Match the following substances with their roles in solubility enhancement:
Match the following substances with their roles in solubility enhancement:
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What is the primary mechanism of solubility enhancement through co-solvency?
What is the primary mechanism of solubility enhancement through co-solvency?
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Weak electrolytes are highly soluble in water.
Weak electrolytes are highly soluble in water.
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Name a common cosolvent used in drug formulation.
Name a common cosolvent used in drug formulation.
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Study Notes
Solubility and Distribution Phenomena
- Solubility phenomena describe the processes and principles governing the dissolution of a solute in a solvent to form a homogeneous solution.
- This involves solute-solvent interactions, leading to uniform distribution of solute particles within the solvent.
- Solubility is a fundamental concept representing the maximum amount of solute that can dissolve in a solvent at a specific temperature and pressure.
- Factors affecting solubility include:
- Molecular interaction (hydrogen bonding, van der Waals forces, ionic interactions).
- Temperature (most solids are more soluble at higher temperatures).
- Pressure (gases are more soluble at higher pressures).
- Nature of solute and solvent ("like dissolves like"): Polar solutes dissolve in polar solvents, and non-polar solutes dissolve in non-polar solvents.
Terminologies
- Solute: The dissolved component (less abundant in the solution).
- Solvent: The component in which the solute is dissolved (more abundant in the solution).
- Solution: A mixture of two or more components forming a homogeneous mixture.
Solubility Expressions
- Solubility can be expressed as percentage, molarity, and molality.
- Percent weight by weight (%w/w): Grams of solute dissolved in 100 grams of solution.
- Percent volume by volume (%v/v): Milliliters of solute dissolved in 100 milliliters of solution.
- Percent weight by volume (%w/v): Grams of solute dissolved in 100 milliliters of solution.
- Molarity: Moles of solute per liter of solution.
- Molality: Moles of solute per kilogram of solvent.
- USP (United States Pharmacopeia) solubility definitions: Provides the volume of solvent required to dissolve a specific amount of solute (e.g., 1 g of boric acid dissolves in 18 mL of water).
Types of Solubility
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Solubility of Gases in Liquids
- The amount (or concentration) of gas dissolved in a liquid at equilibrium.
- Some gas remains in a gaseous phase above the liquid.
- Includes hydrochloric acid and effervescent preparations containing carbon dioxide.
- Factors affecting solubility of gases in liquids: The mass of gas molecules, pressure, temperature, presence of salt.
- Henry's Law: Solubility is directly proportional to the partial pressure of the gas at a constant temperature.
- Temperature and solubility of gases: Solubility decreases as temperature increases.
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Solubility of Liquids in Liquids
- Mixing of two or more liquids to form solutions used in pharmaceutical preparations. (e.g., alcohol and water forming hydroalcoholic solutions).
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Solubility of Solids in Liquids:
- Most common type encountered in pharmaceutical solutions.
- Mixtures of various solutes and solvents.
Ideal and Real Solutions
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Ideal solutions:
- No attraction between solute and solvent molecules.
- No change in properties other than dilution on mixing.
- No heat absorbed or released during mixing.
- Examples include benzene + ethylene chloride, and ethyl bromide + ethyl iodide.
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Real (Non-ideal) solutions:
- Deviations from ideal behavior due to differences in intermolecular forces.
- "Cohesive" forces between like molecules may be stronger than "adhesive" forces between unlike molecules.
Factors Influencing Solubility
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Temperature: Solubility of solids generally increases with temperature. The effect on gases is reversed: solubility decreases as temperature increases..
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pH: Affects the ionization of weak electrolytes.
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Particle Size (Surface Area): Smaller particles dissolve faster.
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Crystal Properties:
- Polymorphs: Different crystalline forms of the same substance with varying physical properties (melting point, solubility).
- Amorphous compounds: Non-crystalline; generally dissolve faster than crystalline forms
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Molecular size: Larger molecules usually are less soluble.
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Branching (Organic Compounds): More branching typically increases solubility due to reduced molecular size.
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Functional Groups: Hydrophobic (non-polar, dissolving in non-polar solvents) and hydrophilic (polar, dissolving in polar solvents) influence a molecule's overall solubility.
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Surfactants: Substances that have both hydrophobic and hydrophilic regions (amphiphilic), influence solubility by altering surface tension and interfacial forces.
Solubility Enhancement Techniques
- Complexation: Forming stable complexes with ligands—like cyclodextrins—to increase solubility.
- Cosolvency: Using a mixture of solvents to increase solubility, usually used for poorly water soluble drugs.
Distribution Phenomena
- Distribution: Refers to the distribution of solute between two immiscible liquids.
- Partition Coefficient (K or P): A ratio of the concentrations of a substance in the two phases at equilibrium; reflects lipophilicity.
- Shake Flask Method: A common technique to determine partition coefficients (e.g., octanol and water).
- Octanol is frequently used as a model for biological membranes in the determination of drug distribution.
Applications of Distribution Concepts
- Oil-water systems preservation, drug absorption/distribution, extracting active ingredients.
Important Concepts Summarized
- Solubility is the maximum amount of a substance that can dissolve in a given amount of solvent.
- Solubility is influenced by factors such as temperature, pH, particle size, the nature of the solute and solvent, and by various techniques (complexation, cosolvency) to improve solubility.
- Partition coefficient is determined to predict or quantify lipophilicity, often used to determine drug distribution.
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Description
This quiz explores the concepts of solubility and the factors affecting the dissolution of solutes in solvents. You will learn about molecular interactions, temperature, pressure, and the principle of 'like dissolves like'. Test your understanding of how these phenomena operate in creating homogeneous solutions.
