Excipients Flashcards
Excipient Uses
- Help dosing accuracy
- Control rate of absorption
- Protect, support or enhance stability, bioavailability or acceptability
- Assist in product identification
- Enhance other attributes, e.g. shelf life
Cosolvents & Cosolvency: Use
- Cosolvency – when a solute is more soluble in a mix of solvents than alone.
- Cosolvents – combination of solvents which increase the solubility of the solute, can allow for the use of no water.
Purpose of use: - Obtain (aq) based systems where the drug solubility is higher than the (aq) solubility.
- Formulate higher [drug]
- Improve stability of the formulation
Cosolvency & Desolubilization
- Addition of a cosolvent increases the solubility of a nonpolar & semipolar solute in water.
- As the solute becomes more polar, cosolvency becomes less efficient
- It will decrease the solubility of a polar solute in water
How Cosolvents Work
Cosolvents decrease H bond density of (aq) systems, reducing cohesive interactions with water, reducing solution polarity.
The solution is less effective than H20 squeezing out non-polar solutes. Cosolvents cause exponential increase in solubility with increasing [cosolvent].
Cosolvency: pH & Solubility
- When the pH of this solution is adjusted to produce mostly unionized molecules, exceeding the solutions’ solubility produces precipitation.
- The solubility of weak electrolytes or non-polar compounds in water can be improved by the addition of water –miscible solvent in which the compound is soluble.
Cyclodextrins (CDs)
Cyclodextrins (CD) - are enzymatically modified starches.
*Their units form a ring:
- a-CD a 6 units ring,
- b-CD, 7 units ring
- g-CD, 8 units.
Some CD are:
- Solubilisers
- Have strong affinity for cholesterol & haemolytic
- Can be used for helping controlled release of medicines
How Cyclodextrins work
From insertion of the non-polar portion of one molecule being incorporated into the non-polar cavity of a water soluble molecule/s.
The driving force: reduce the non-polar-water interfacial area by inserting the solute (guest) into the complexing agent (host).
What are Surfactants (Surface Active Agents)
Reduce the surface tension at an interface without requiring the [large] that could blur the distinction between solvent & solute.
At [high] they may undergo micellization
Surface activity:
The lower the [required] for a given effect, the better surface-activity properties of a solute.
Surfactant Structure
Most surfactants have a polar head group & a nonpolar chain, or hydrophilic & lipophilic regions, as these produce the greatest reduction to interfacial tension, & have their lowest potential at the phase boundary.
Balance of the regions determines:
– The surfactant solubility in water & oil
– Its applications
– Its place on the scale of HLB (Hydrophile-Lipophile Balance)
Surfactant - Polar region’s effects
Polar region:
* Affinity for water
* Capable of pulling long hydrophobic hydrocarbon chains into water
* The polar group must be sufficiently polar to hold the nonpolar region of the surfactant in solution
Emulsifiers
Emulsification- addition of a surfactant reduces interfacial tension between oil & water.
Emulgent - surfactants used to stabilize emulsions
- Each oil requires an emulgent of specific HLB to ensure a stable emulsion
- Emulsifier’s required HLB vary with temp. due to solubility of lipophile & hydrophile vary with temp.
Effect is greater on non-ionic surfactants due to H-bond’s weakening, decreasing solubility. At low temp is water soluble, at high oil soluble.
Diluents (Bulking Agents):
Inert substances added to the API to make a reasonable sized tablet. Some chosen based on physical properties. Can make tablet physically stronger but can be sensitive to lubricant or moisture.
Lubricants:
Prevent adherence of the formulation to punches & dyes & ensure smooth ejection of the tablet from the dye. Some act as anti-adherents & flow aids.
But needs more processing steps, is incompatible with some drugs, & [greater] disintegration time, drug dissolution & weakens the bonding forces.
Glidants (Flow agents):
materials added to improve flow properties of granules by reducing inter-particulate friction, which reduces cohesion/adhesion, which determines flowability. Also smooths the surface of the tablet. Most commonly used & effective is fumed silica.
