Lecture 4 - Disperse Forms (Part 1 - Suspensions) Flashcards
What do disperse systems refer to?
liquid preparations containing undissolved or immiscible drug distributed throughout the vehicle
Dispersed substance known as ______ phase and vehicle know as ______ or _______ phase
dispersed
continuous
dispersing
Solid in liquid :
a suspension
Liquid in liquid :
an emulsion
Solid or liquid in air :
an aerosol
What is the nomenclature of a suspension?
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)
What is a suspension?
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)
In 2002 the USP formed a group to work on clarifying dosage form nomenclature…
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
______ may define a dispersed system
Particle size
Coarse dispersions:
Solute not dissolved completely and is visible
Size >10 μm
ex: Suspensions and emulsions
Fine dispersions:
Solute not completely dissolved
Size 0.5 – 10 μm
ex: Magmas and gels
Colloidal dispersions:
Solute not completely dissolved but not visible
Size 1 nm – 0.5 μm
Will scatter light (Tyndall effect) (when light is placed over it)
Molecular solutions:
Solute completely dissolved in solvent
True solutions do NOT scatter light
Size <1nm
What is the stability of disperse systems?
are thermodynamically UNstable systems
For disperse systems, the larger the particle size…
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
What labels would you use for disperse systems?
Shake Well
This bottle is not full but contains the exact amount prescribed by your physician
Shake well and keep in the refrigerator
What is a Suspension?
Two phase systems of a finely divided solid uniformly dispersed in a liquid phase
What are the properties of a Suspension?
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
What are advantages of a Suspension as a dose form?
- 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
What are disadvantages of a Suspension?
- 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
For suspension you might have to convert drug –> salt form. Why?
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
What are the desirable attributes of a suspension?
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
What is the Stoke’s Law?
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)
Although an idealized law, Stokes’ law indicates that rate of sedimentation is:
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
What are Floccules?
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
How do floccules form?
May form floccules by adding a small quantity of surfactant or sometimes electrolytes which at specific concentrations may neutralize surface charges
Because particle size with floccules now larger…what should we add?
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)
What is Thermodynamic instability?
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).
A surface will always try & minimize its energy. How can this be done?
- 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
What is the relationship b/t contact angle & surface energy?
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).
A product available only as a solid oral dose form can be a problem for who?
for elderly and children
A liquid oral dose form can be prepared but must consider stability and bioavailability
Also consider preservative, flavor and color
What is the typical procedure to make a solid oral dose form into a liquid one?
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
What are things to remember when making a solid oral dose form into a liquid one?
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
Some commercial preparations supplied as dry powder or granules. What do they contain?
Contain medication and excipients
When dispensing, powder loosened then measured volume of purified water added in portions with shaking to prepare suspension
Suspensions or structured vehicle may contain:
Active ingredient
Wetting agent
Suspending agent
Flocculating agent
Protective colloid
Sweetener Preservative
Buffer system
Color agent
Flavor agent
Antifoaming agent
