Lecture 6

Question 1

Determinants on States of Matter (3)

Answer 1

1. Distance between molecules (fundamental determinant)
   At certain temperatures & pressures, states depends on opposing entities:
2. KE of particles
3. Strength of attraction between particles

Question 2

3 States of Matter

Answer 2

1. Gases - total disorder, empty space, complete freedom of particles to move far apart
2. Liquid - disorder, particles/clusters of particles are free to move relative to each other, closer together than gas
3. Solid - Ordered, fixed position, close together

Question 3

Condensed Phases

Answer 3

Solid and Liquid

Question 4

State Transition Phrases (6)

Answer 4

1. Condensation - gas to liquid (cooling and increased pressure)
2. Vaporization - liquid to gas (heating and decreased pressure)
3. Freezing - liquid to solid (cooling)
4. Melting - solid to liquid (heating)
5. Sublimation - solid directly to gas
6. Deposition - gas directly to solid

Question 5

Vaporization in Pharmacy

Answer 5

• Active drug is dissolved or dispersed in a low boiling point solvent under pressure
• Upon opening, solvent goes to room pressure and instantly “boils” making an aerosol for inhalation
• Solvent utilized is designed to minimize the rate of expansion, speed of particles, and impact on the throat

Question 6

Gases Properties

Answer 6

Can predict a gas’ behavior based on:

1. Pressure
2. Volume
3. Amount
4. Temperature
   * *smaller the size and the more stable the particle the more likely it is to be a gas**

Question 7

Pharmaceutical Gases (3)

Answer 7

1 Oxygen - cylinders (heavy), personal liquid, oxygen systems (lighter & complex)

2. Nitrous Oxide (NO2) - used in anesthesia and can be abused (whippets, causes vitamin B12 deprivation)
3. Nitric Oxide (NO) - inhaled for pulmonary arterial hypertension

Question 8

Liquid Properties

Answer 8

• shape of the portion of the container it occupies, does NOT expand to fill container
• virtually incomprehensible
• flows readily
• diffusion occurs slowly

Question 9

Viscosity

Answer 9

• Resistance to Flow. Related to that ease at which particles can move past to each other (crowding and reaction wise)
• Medication developers want viscous solutions to keep them well mixed

Question 10

API

Answer 10

Active Pharmaceutical Ingredient

Question 11

Liquid APIs

Answer 11

• Rare
• weaker IMF than solids, no ionic bonds, maybe some hydrogen bonds
• Fish oil and nitroglycerin are examples of some liquid APIs
• Premade solutions, not suspensions

Question 12

Solid Properties

Answer 12

• Almost all APIs & excipients are solids
• Retain their own shape & volume
• Virtually incompressible
• Doesn’t flow
• Diffusion occurs EXTREMELY slow

Question 13

Solid Arrangements

Answer 13

1. Crystalline - highly ordered arrangements (low energy)

2. Amorphous - no particular order in the arrangement (high energy). More penetrable by solvent/degradation agents.

Question 14

Is Amorphous -> Crystalline favorable?

Answer 14

No. This change can cause major dissolution and bioavailability shifts for a medication that can impact a patient in a variety of ways.

Question 15

Crystalline Properties

Answer 15

• Covalent bonds
• weaker attractive forces hold molecules together
• most common pharmaceutical preparation

Question 16

Co-Crystal/Solvent of Crystallation

Answer 16

• Often water promotes dissolution and sometimes degradation
• If organic the solvent could be toxic
• If heat, drives off water and crystal becomes amorphous

Question 17

Dissolution Depends on: (3)

Answer 17

1. IMF & its interactions with water
2. Solid form of API
3. Particle size of API

Question 18

Polymorphs

Answer 18

• APIs crystallizing in different ways that can vary by temperature, solvents, and concentration
• leads to differences in solubility that goes on to affect dissolution & absorption
  ex: ritonavir solution, new polymorph “formed” that was 400% less soluble and costed millions to fix in the middle of the AIDS epidemic

Question 19

Dissolution & IMFs

Answer 19

• The stronger the bonds the greater its interaction with water and the more it will dissolve
• Ionic = strongest (salts)
• Van der Waals = weakest

Question 20

Particle Size Affects

Answer 20

• Increases Surface Area : Mass ratio (more to interact with environment)
• Faster dissolution
• Faster degradation
• Poor powder properties, but can make aerosols

Question 21

Crystal v.s. Amorphous

Answer 21

Crystal:
1. Slower dissolution
2. More resistance to degradation
3. Changes from crystalline => amphorous is rare and requires heating
Amorphous:
1. Higher SA:M than crystal
2. Fast dissolution
3. Fast degradation
4. High energy state that can undergo crystallization over time (unfavorable)