Lecture 4 - Disperse Forms (Part 1 - Suspensions)

Question 1

What do disperse systems refer to?

Answer 1

liquid preparations containing undissolved or immiscible drug distributed throughout the vehicle

Question 2

Dispersed substance known as ______ phase and vehicle know as ______ or _______ phase

Answer 2

dispersed

continuous

dispersing

Question 3

Solid in liquid :

Answer 3

a suspension

Question 4

Liquid in liquid :

Answer 4

an emulsion

Question 5

Solid or liquid in air :

Answer 5

an aerosol

Question 6

What is the nomenclature of a suspension?

Answer 6

Word suspension is now the USP-designated term for dosage forms that are solid-liquid dispersions

Historically other terms have been used as names for suspensions such as:
- milk (e.g., milk of magnesia)
- magma (e.g., bentonite magma) lotion (e.g.,
- hydrocortisone lotion)
- syrup (e.g., doxycycline syrup)

Question 7

What is a suspension?

Answer 7

usually made up of a solid dispersed in a liquid, in which the solid isn’t dissolved (i.e. not a solution - it’s not dissolved, it’s just dispensed)

Question 8

In 2002 the USP formed a group to work on clarifying dosage form nomenclature…

Answer 8

Proposed that dosage forms be named by route of administration (e.g. oral, topical) plus their physical system (e.g. tablet, solution, suspension)
- For example the name White Lotion USP was changed to the more descriptive Zinc Sulfide Topical Suspension USP

Question 9

______ may define a dispersed system

Answer 9

Particle size

Question 10

Coarse dispersions:

Answer 10

Solute not dissolved completely and is visible

Size >10 μm

ex: Suspensions and emulsions

Question 11

Fine dispersions:

Answer 11

Solute not completely dissolved

Size 0.5 – 10 μm

ex: Magmas and gels

Question 12

Colloidal dispersions:

Answer 12

Solute not completely dissolved but not visible

Size 1 nm – 0.5 μm

Will scatter light (Tyndall effect) (when light is placed over it)

Question 13

Molecular solutions:

Answer 13

Solute completely dissolved in solvent

True solutions do NOT scatter light

Size <1nm

Question 14

What is the stability of disperse systems?

Answer 14

are thermodynamically UNstable systems

Question 15

For disperse systems, the larger the particle size…

Answer 15

the greater the tendency to separate from the dispersing phase

solids tend to settle while liquids rise to the top

For dosing accuracy the dispersed phase should be restored to uniform distribution throughout the dispersing phase with moderate agitation of the container

Question 16

What labels would you use for disperse systems?

Answer 16

Shake Well

This bottle is not full but contains the exact amount prescribed by your physician

Shake well and keep in the refrigerator

Question 17

What is a Suspension?

Answer 17

Two phase systems of a finely divided solid uniformly dispersed in a liquid phase

Question 18

What are the properties of a Suspension?

Answer 18

Particle size 10 –50 μm (or larger)

Continuous phase usually aqueous and solute has minimal solubility in it

Suspensions may be sweetened and flavored for oral use

Suspensions for topical use may be called lotions

Question 19

What are advantages of a Suspension as a dose form?

Answer 19

• Ease of swallowing for patients who cannot swallow solid dose forms
• Flexibility in giving doses of different size
• Disagreeable taste may be masked
• Drug may have *increased stability

Question 20

What are disadvantages of a Suspension?

Answer 20

• Physically unstable and will separate over time
• If homogeneity not restored before use dosing inaccuracy will result
• Patient may not like mouth-feel of product especially if particle size is relatively large

Question 21

For suspension you might have to convert drug –> salt form. Why?

Answer 21

if you want to make a solution, you can use this form, but if you want to make a suspension where you don’t want the solute to completely dissolve in water, you have to use a salt form that has a less water solubility

Question 22

What are the desirable attributes of a suspension?

Answer 22

Should settle slowly and be readily re-dispersed with gentle shaking

The particle size should remain fairly constant over the shelf-life of the product

The suspension should pour readily and evenly from its container

Question 23

What is the Stoke’s Law?

Answer 23

law/equation that describes the factors that are affecting the rate of sedimentation (AKA factors that are affecting the rate of sedimentation)

want a LOW rate of sedimentation (& can change these parameters to get what we want)

Question 24

Although an idealized law, Stokes’ law indicates that rate of sedimentation is:

Answer 24

A function of particle size (small particles settle more slowly)

An inverse function of viscosity (more viscous solutions settle more slowly)

Therefore, the *rate of sedimentation can be slowed by (1) reducing the particle size and/or (2) increasing the viscosity of the medium

If particle size is very small may be tendency for caking or agglomeration
- This prevents easy redispersion of settled particles
- Forming floccules is a way to prevent caking

Question 25

What are Floccules?

Answer 25

Loose aggregation of particles (instead of particles coming together with electrostatic forces, you want the particles to come together with VDW forces (weak forces) Formulation strategy which is sometimes used - Held together by weak particle-particle bonds (van der Waals) - Form higher sediment volume than non-flocculated suspension - Loose structure allows easy redispersion

Question 26

How do floccules form?

Answer 26

May form floccules by adding a small quantity of surfactant or sometimes electrolytes which at specific concentrations may neutralize surface charges

Question 27

Because particle size with floccules now larger...what should we add?

Answer 27

need to add a viscosity-increasing agent - Should rheologically be pseudoplastic – higher viscosity at low shear rates (storage, just after shaking, pouring) low viscosity at high shear rate (shaking)

Question 28

What is Thermodynamic instability?

Answer 28

Want small particle size but comminution process generates free surface energy - In bulk form atoms are stable and have a balanced set of bonds/interactions but surface atoms have incomplete set of interactions and thus unrealized bonding energy. ‘Surface energy’ is a relative measurement of the energy at the surface (which is a result of this incomplete bonding).

Question 29

A surface will always try & minimize its energy. How can this be done?

Answer 29

- This can be done by adsorbing a material with a lower energy onto its surface - Generally the higher the surface energy, the more hydrophilic the surface - Bonds in hydrocarbons weak Vander Waals so surface hydrophobic Other way is to reduce surface area by particles coalescing together

Question 30

What is the relationship b/t contact angle & surface energy?

Answer 30

Substance with high surface energy has good wetting and a low contact angle. Surfaces with high surface energy include materials held together by stronger bonds (eg. Ionic and covalent).

Question 31

A product available only as a solid oral dose form can be a problem for who?

Answer 31

for elderly and children A liquid oral dose form can be prepared but must consider stability and bioavailability Also consider preservative, flavor and color

Question 32

What is the typical procedure to make a solid oral dose form into a liquid one?

Answer 32

Typical procedure is to powder/empty appropriate number of tablets/capsules Using a mortar and pestle and an appropriate levigating agent like glycerin, prepare a smooth paste Add structured suspending vehicle in portions and add to measuring cylinder Make to volume, mix by inversion and dispense into suitable bottle

Question 33

What are things to remember when making a solid oral dose form into a liquid one?

Answer 33

Best to use commercially-prepared vehicle like Ora- Sweet - May use syrup or methylcellulose-type vehicle but must consider addition of preservative With infants and neonates must minimize exposure to preservatives, alcohol and propylene glycol Without published stability information, USP <795> directs that expiration date for aqueous product no more than 14 days in the refrigerator

Question 34

Some commercial preparations supplied as dry powder or granules. What do they contain?

Answer 34

Contain medication and excipients When dispensing, powder loosened then measured volume of purified water added in portions with shaking to prepare suspension

Question 35

Suspensions or structured vehicle may contain:

Answer 35

Active ingredient Wetting agent Suspending agent Flocculating agent Protective colloid Sweetener Preservative Buffer system Color agent Flavor agent Antifoaming agent