AERSOLS

Question 1

AEROSOL DOSAGE FORMS

Answer 1

Pressurized dosage forms that, upon actuation, emit a fine dispersion of liquid or solid materials containing one or more active ingredients in a gaseous medium

Question 2

Inhalants

vicks / ammonia

amyl nitrate

Answer 2

Drug has a

• *HIGH VAPORPRESSURE**
• do not need propellant*

does not need anything for the
drug to be aerosoled

Question 3

What Dosage Form?

Pressurized container

Solutions + Suspensions
CONTAINS PROPELLANT
admin by actuation

ex. Asthma drugs

Answer 3

AERSOL DOSAGE FORMS

includes
MDI’s

Question 4

What Dosage Form?

Solid formulation in capsule / cartridge

not pressurized / no propellant

adminstered by ACTUATION

asthma drugs

Answer 4

DRY POWDER INHALER

DPI

Question 5

What Dosage Form?

Drug solution administede with NEBULIZER

VENTURI Principle

Air pressure & droplet size important

Answer 5

INHALATION SOLUTION

Question 6

Ideal respiratory delivery system

MDI & DPI

Answer 6

Formulation
stable formultion + package meeting design requirements

• *Bioavailability**
• *~1 micron partical size**

Compliance
ease of use & clinical advantages
counters / memory

Question 7

• *Aerosol**
• *Properties**

Answer 7

• *Particle Size**
• *micronization –> ~1 micron size**

Physical Properties
density / spgr

• *Vapor Pressure**
• *escaping tendency // volatile CCl3F**

Chemical + Physical Stability
chemical reactivity / no rxn with package

Question 8

Sealed canister containing formulation and propellant. Used in conjunction with an actuation device.

Answer 8

AEROSOLS

MDI / pMDI

could be continious or MDI

RAPID onset of action / EXACT dose

convenient / lower dose

Question 9

Aerosol
Packaging / Components

Answer 9

RX products approved by FDA

CONTAINER
glass / pvc coated glass / metal / resin

VALVE Assembly
meter chamber for MDI
dip tube = al / resin / nlon

MDI Mouthpiece –> Actuator

MDI Spacer

Question 10

Two-Phase System

Answer 10

Liquid propellant and vapor propellant

HIGH PROPELLANT CONTENT

Appropriate propellant combination

Question 11

Three Phase System

Answer 11

WITH BALOON == WITH DRUG IN IT
drug that is SOLUBLE IN WATER

Aqueous, liquid propellant, and vapor propellant

Variable drug and propellant content

Appropriate propellant combination

Question 12

Compressed Gas System

Answer 12

GAS PROPELLANT
N2 / CO2 / NO

no liquid component

HIGH DRUG Cntent

Question 13

Propellants

Answer 13

Non-polar Liquid or Gas

CFC =
no longer used = deplete ozone

Non-CFC

CCl₃F Trichlorofluoromethane (P-11) = propellant

CCl₂F₂ Dichlorodifluoromethane (P-12)

C₂Cl₂F₄ Dichlorotetrafluoroethane (P-114)

Question 14

Non-CFC Propellant

NAMING

CCl₂F₂

Answer 14

CCl₂F₂ = P-12

C = 1 - 1 // H = 0 +1 // F = 2
0 // 1 // 2

1^st digit on right is number of F

2^nd digit is 1 plus number of H

3^rd digit is 1 minus number of C

Question 15

Aerosol Formulation
when to use

SOLUTION or SUSPENSION

Answer 15

If the API is SOLUBLE in the PROPELLANT
V
USE SOLUTION
may add co-solvent –> aid solubility
alcohol /glycerol / propylene glycol

Question 16

Specifications of Aerosols

PRODUCT REQUIREMENTS

Answer 16

Drug Content Assay

Dose UNIFORMITY // Particle size DISTRIUTION

Effect of STORAGE –> particle size

Plume Geometry

Profiling of actuations near canister exhaustion

Question 17

Precautions of Active Ingredients

Nitroglycerin

Answer 17

Nitroglycerin is NOT FOR PULMONARY DELIVERY

Question 18

Precautions of Active Ingredients

Anesthetics

Answer 18

ANESTHETICS ON BROKEN SKIN

Question 19

Respiratory Drug Administration

Answer 19

SYNCHRONIZED
INSIPRATION + ACTUATION

Long -deep breath –> HOLD –> EXHALE

Question 20

Non-pressurized device that, upon activation, delivers a fine particle size material transported by patient inhalation.

Answer 20

DRY POWDERED INHALER

Flovent (fluticasone) Diskus

Serevent (salmeterol) Diskus

Pulmicort (budesonide) Turbuhaler

Question 21

Advantages of DPI

Answer 21

Rapid Onset

AVOID injection / First pass metaolism

PROTEIN absorption

Question 22

DPI Formulation

Answer 22

Micron-Sized Drug in variety of delivery forms:

Crystal Form

Excipient binding / blending

Surfase passivation

Drug-excipient complexes

Question 23

DPI Administration

1. More than 25% of patients have difficulty with unit preparation
2. More than 75% of patients have trouble with inhale, hold breath, exhale through mouth, etc. procedure.

Answer 23

VERY DIFFICULT FOR PATIENTS TO ADMIN

Initiate Dose / Activate Particles

SYNCHRONIZED INHALATION

Dose is Counted

rinse mouth

Question 24

Inhalation Solutions

Answer 24

Commercial products are sterile solutions in glass vials or plastic blow-fill-seal containers.

Products added to nebulizer apparatus.

Nebulizer enables administration of appropriate size droplets by means of the Bernoulli principle and venturi effect.

Question 25

**Advantages of Aerosol Products MDI / pMDI**

Answer 25

**Rapid Onset** **EXACT DOSE** **Convenience**

Question 26

**What dosage form uses a** **METERING CHAMBER?**

Answer 26

**_MDI ONLY_** also needs a **mouthpiece --\> actuatior** **SPACER**

Question 27

**Two Basic Propellant Systems**

Answer 27

* *_LIQUEFIED GAS_** * *in EQ w/ vapor pressure** * *propellant vapor pressure** basis for aerosol use * *_COMPRESSED GAS_** * **DECLINES WITH PRESSURE USE***

Question 28

**Valves** **Continuous Vs Metered Dose**

Answer 28

**MDI = EXACT & REPEATABLE DOSE** **Dip Tube structure --\> product method of use**

Question 29

**Pressurized Ideal respiratory delivery system** (MDI, DPI, and inhalation solutions/devices)

Answer 29

* *_Formulation:_** * *Stable formulation** * *including package** meeting **design requirements** * *_Bioavailability:_** * *Respirable particle delivery (1 micron particle size)** * *_Compliance:_** * *Ease of use and clinical advantages**

Question 30

**_Metered dose inhaler (MDI)_**

Answer 30

**Actuator, mouthpiece**, **metering chamber**, and **dip tube**, and **mouthiece** **_Two-phase system:_** Liquid propellant and vapor propellant. **High propellant content** * *_Three-phase system:_** * *Aqueous**, liquid propellant, and vapor propellant. Barrier (Bag-in-can, can-in-can) **_Appropriate propellant combination_**

Question 31

* *_Dry powder Inhalers (DPI) --_** * **_Non-pressurized device_*** that, **upon activation**, delivers a **fine particle size material** transported by **patient inhalation.**

Answer 31

**Solids formulation** in **capsule** or c**artridge** **1 micron particle siz**e with carrier system ***_Not pressurized – no propellant_*** Administered by actuation

Question 32

**_AEROSOL PHARMACIST COUNSELING_**

Answer 32

**_MDI and DPI relatively difficult for patient use._** - * *anesthetics on broken skin, * _Nitroglycerin not for pulmonary delivery_*** Respiratory drugs -- Synchronize inspiration with actuation Long deep breath – hold – exhale. Repeat after a few seconds **_Hold container in correct position – Upright or inverted_** **Shake container to mobilize particles** **Firm pressure on actuator** **_Prime delivery device --first use (or after storage)_**

Question 33

**Ostwald Ripening**

Answer 33

**_Particle Size INCREASE_** particles **crystallize or deposit into larger sizes** **ISSUE WITH TEMPERATURE for AEROSOLS STORAGE**

Question 34

**Describe the propellant system that would be used for a MDI. Explain in one sentence why is this an appropriate system**

Answer 34

**_Liquified gas._** **Vapor pressure remains constant throughout product use**. Key point is constant vapor pressure or provides uniform dose throughout entire container.

Question 35

**Describe two different applications of vapor pressure in inhalation dosage forms**

Answer 35

**MDI = Vapor pressure is the propellant** **Inhalants DRUG ITESELF has vapor pressure** **VICKS**, you can just **inhale it**

Question 36

1. **Three reasons why patents must store aerosol dosage forms at the specific storage temperature**

Answer 36

**Too cold could affect _vapor pressure propellant_** **Too hot _could cause explosion – too much pressure_** **_Drug stability –_ too hot could accelerate drug degradation reactions** **_Particle size increase_ due to _temperature cycling_ or _Ostwald ripening._**

Question 37

1. **Why use a cosolvent in an MDI formulation? Provide an example cosolvent molecule**

Answer 37

A cosolvent enables an i**nsoluble API to dissolve** thereby providing a **_solution dosage form instead of a suspension dosage form._** Example cosolvents are **ethanol, propylene glycol, or other glycol** (accept other semi-polar solvents).

Question 38

**Why calculate the vapor pressure of the propellant mixture in an aerosol dosage form?**

Answer 38

**_The vapor pressure must be appropriate for the intended use._** **Surface sprays, room sprays, sprays used for long distance spraying, foams, MDI, etc.** **all have different vapor pressure requirements.** **Also accept that the vapor pressure must not be too strong or powerful for human administration to the throat and lungs.**

Question 39

**What is the effect of the _dissolved formulation ingredients_** **on the _vapor pressure_ of a pharmaceutical aerosol product? Why?**

Answer 39

**_Vapor pressure lowering._** ## Footnote **Vapor pressure is a colligative property which is affected by molecules in solution.**

Question 40

**The propellant mechanism in a compressed gas aerosol and in an MDI aerosol are identical.**

Answer 40

**_False._** The **MDI uses an equilibrium between liquid and vapor propellant**. The **compressed gas uses only gas under pressure**

Question 41

**Using micronized drug in a nasal spray formulation will enable the API to reach the alveoli in the lung.**

Answer 41

**False. The micronized drug gets to the lung in an MDI, but not in a nasal spray.**