Chapter 13- Solubility

Question 1

Attractive Forces

Answer 1

Forces that pull particles together in chemical systems.

Question 2

Solubility

Answer 2

Solubility is a critical factor in pharmaceutical solutions because it determines how effectively the active pharmaceutical ingredient (API) can be dissolved in a solvent. If an API is not soluble in a chosen solvent, it may require alternative formulation methods or solvents, impacting drug development and efficacy.

Question 3

Pharmaceutical Solutions

Answer 3

Solutions used in the pharmaceutical industry, typically involving a solute (active pharmaceutical ingredient) dissolved in a solvent (usually water or another suitable liquid).

Question 4

Hydrogen Bonds:

Answer 4

Definition: Hydrogen bonds are a type of chemical bond in which a hydrogen atom is attracted to a highly electronegative atom (such as oxygen, nitrogen, or fluorine) in another molecule. This results in a relatively strong intermolecular force.

Impact on Drug Solubility: Hydrogen bonds play a critical role in drug solubility. If a drug can form hydrogen bonds with the solvent molecules, it tends to have higher solubility. This is particularly important for polar drugs that can engage in hydrogen bonding with polar solvents.

Question 5

Van der Waals Forces:

Answer 5

Definition: Van der Waals forces are weak intermolecular forces that include London dispersion forces, dipole-dipole interactions, and induced dipole-induced dipole forces. They result from temporary fluctuations in electron distribution within molecules.

Impact on Drug Solubility: Van der Waals forces influence drug solubility, especially in nonpolar or less polar solvents. These forces can affect how well drug molecules interact with each other and with the solvent. For nonpolar drugs, van der Waals forces may be the dominant force impacting solubility.

Question 6

Ion-Dipole Interactions:

Answer 6

Definition: Ion-dipole interactions occur when ions (charged particles) interact with polar molecules. These interactions are important in solutions where both ionic compounds and polar solvents are present.

Impact on Drug Solubility: In pharmaceutical solutions containing ionic drugs and polar solvents, ion-dipole interactions are crucial. These interactions help the ionic drug dissolve in the polar solvent, impacting drug solubility and formulation.

Question 7

Bioavailability

Answer 7

Definition: Bioavailability is the fraction of an administered dose of a drug that reaches the systemic circulation in a form that allows it to have a pharmacological effect. It is influenced by factors such as drug solubility, absorption, and metabolism.

Impact on Drug Solubility: A drug’s solubility directly affects its bioavailability. If a drug has low solubility, it may not dissolve well in the gastrointestinal fluids, leading to reduced bioavailability and potentially lower therapeutic efficacy.

Question 8

Solutes

Answer 8

These are the active medicinal agents that are intended to be dissolved in the solution.

Question 9

Additional Agents

Answer 9

These can include ingredients added to enhance the properties of the solution, such as color, flavor, sweetness, and stability.

Question 10

Solvent or Solvent System

Answer 10

The liquid medium in which the solutes are dissolved. The choice of solvent or solvent system is crucial in pharmaceutical formulation.

Question 11

Solubility

Answer 11

Refers to the ability of a solute (the drug) to dissolve in a particular solvent or solvent system to form a homogeneous solution under specific conditions.

Question 12

Solute-Solute Forces:

Answer 12

These forces are interactions between the drug molecules. They can affect how well the drug dissolves and stays in solution.

Question 13

Solvent-Solvent Forces:

Answer 13

These forces describe interactions between the solvent molecules. The nature of the solvent can impact the solubility of the drug.

Question 14

Single Solvent Therapeutic

Answer 14

Refers to the use of a single solvent for the formulation of a therapeutic solution. The choice of solvent is crucial for the drug’s effectiveness.

Question 15

Solubility Depends on Solute-Solvent Attraction:

Answer 15

The strength of attraction between the drug and the solvent significantly influences solubility.

Question 16

Calcium Hydroxide Topical Solution, USP

Answer 16

Solute: Calcium Hydroxide

Solvent: Purified Water

Solution: has the API (calcium hydroxide)

Concentration: 140 mg/ 100mL

An example of a solution with relatively low solubility (140 mg of solute per 100 mL).

0.14% w/v
0.14 g solute in 100mL solution
this is the solubility of calcium hydroxide at room temperature
VERY LOW SOLUBILITY

Question 17

Potassium Iodide Oral Solution, USP

Answer 17

Solute: Potassium Iodide

Solvent: Purified Water

Solution: 100g of solute in 100mL

An example of a solution with high solubility (100 g of solute per 100 mL).

100% w/v
100 g of solute in 100 mL solution

Question 18

Factors that affect solubility

Answer 18

Solute
Solvent
Solution

: Factors that influence the solubility of a solute in a solvent, including the choice of solute, solvent, pH, and temperature.

Question 19

Solute

Answer 19

Solubilizing agent.

The choice of solubilizing agent can significantly impact the solubility of a solute.

Some substances can enhance the solubility of certain solutes. In the case of Iodine Topical Solution, the iodine granules are the solute.

The chemical form of the solute can also affect solubility. Some salts of a medicinal agent may have different solubilities in a given solvent.

Question 20

Solvent

Answer 20

The liquid or substance in which the solute is dissolved.

The choice of solvent is crucial. In some cases, you can improve solubility by substituting part or all of the solvent.

In the case of the Iodine Topical Solution, purified water is used as the solvent.

Question 21

Solution

Answer 21

pH: The pH of the solution can impact the solubility of certain substances. Adjusting the pH can make some compounds more or less soluble.

Temperature: Temperature plays a role in solubility. Generally, higher temperatures can increase the solubility of many solutes.

Question 22

Iodine granules solubility in water

Answer 22

They are only soluble to the extent of 1 g in about 3,000 mL. Using only these two agents, the maximum
concentration possible would be approximately 0.03% of iodine.

Question 23

Iodine Topical Solution, USP

Answer 23

Through the use of an aqueous solution of potassium iodide or sodium iodide as the solvent, much larger amounts of iodine may be dissolved as the result of the formation of a water-soluble complex with the iodide salt.

Prepared to contain about 2% iodine and 2.4% sodium iodide.

Question 24

Very soluble

Answer 24

<1

Question 25

Freely Soluble

Answer 25

1-10

Question 26

soluble

Answer 26

10-30

Question 27

sparingly soluble

Answer 27

30-100

Question 28

slightly soluble

Answer 28

100-1000

Question 29

very slightly soluble

Answer 29

1000-10,000

Question 30

practically insoluble or insoluble

Answer 30

> 10,000

Question 31

What can be changed in regards to the SOLUTE to increase solubility?

Answer 31

- solubilizing agent (excipient) -using a chemical salt of the API (medicinal agent)

Question 32

Is it preferred to alter the solubility by changing the API or changing the solvent(s)?

Answer 32

preferred to change the solvents.

Question 33

How can the solvent be altered to adjust the solubility of a drug?

Answer 33

substitution (in part or whole) ie: use of a cosolvent is done most of the time

Question 34

Q Explain how the SOLUTION ITSELF can be altered to adjust the solubility of the API

Answer 34

changing the pH or the temperature of the final solution.

Question 35

pH of the solution is adjusted based on what equation?

Answer 35

hendersen hasselbach equation

Question 36

why is changing the temperature of the final solution NOT really used to increase solubility?

Answer 36

because the solution is stored at room temperature usually and the solubility will change once the heat is removed in the laboratory setting

Question 37

Explain how altering the solution of iodine granules + purified water can increase solubility.

Answer 37

iodine granules by itself is not very soluble in purified water. 1 g of solute in 3000mL solution (0.033%w/v) however, Iodine Topical Solution USP has the iodine granules (2%) and 2.4% of sodium iodide (SERVES AS A SOLUBILIZING AGENT) as the solutes and purified water as the solvent. this makes the solution much more soluble SOLUTES: iodine and sodium iodide (solubilizing agent; excipient) SOLVENT: the same – purified water

Question 38

“parts of solvent required to dissolve 1 part of the solute” be specific…

Answer 38

the mL of solvent required to dissolve 1 g of solute

Question 39

Explain what happens when you convert a drug to its salt form

Answer 39

when a drug is converted to its salt form, the drug’s solubility in water is increased due to the “like dissolves like” principle (both are polar) however, converting to salt form means that if alcohol is the solvent, much more of it is required to dissolve this salt form of the drug.