Exam 1 - Liquid Dosage Forms: Solution Flashcards
Components of Solution Dosage Forms
- Active ingredient
- Solvent
- Buffer
- Preservative
- Antioxidant, chelating agent
- Flavor and sweetener (sucrose + sorbitol)
Buffer Principle
A solution of a weak acid and a salt of its conjugate base
Weak acid removes added base (OH-):
HA + OH- H2O + A-
Salt removes added acid (H+):
A- + H3O+ HA + H2O
Common pharmaceutical buffers
- acetic acid (4.76)
- citric acid (3.15, 4.78, 6.40)
- glycine (2.35, 9.78)
- phosphoric acid (2.12, 7.21, 12.67)
Antimicrobial preservatives
- Purposes
- **Protect patient from pathogens
- **Maintain potency and stability of dosage forms
-Mechanism of action
**Preservatives adsorb to the bacterial membrane and disrupt the membrane. The membrane is lipophilic and has a net negative surface charge.
**Adsorption due to lipid solubility
Alcohols, acids, esters
***Adsorption due to electrostatic attraction
Quaternary ammonium compounds
Bacterial content allowed in various dosage forms:
Ampule
Must be sterile, single dose, no preservative needed.
Bacterial content allowed in various dosage forms:
Multiple dose vials
Must be sterile, may contain up to 10 doses, need a preservative to kill microorganisms introduced during use.
Bacterial content allowed in various dosage forms:
Opthalmic solutions
Must be sterile, must contain a preservative if packaged in multiple dose container.
Bacterial content allowed in various dosage forms:
Oral liquids
Need not be sterile but should not contain pathogens. FDA limits the number of organisms (e.g., E. coli) to be less than 100 per mL. Need preservative for multiple dose packages.
Bacterial content allowed in various dosage forms:
Oral Solids
Less likely to carry bacteria than liquid forms. Pathogen contamination is still a concern (e.g., Salmonella). Test raw materials and be sure that the manufacturing facility is clean.
Ideal Preservatives
Effective in low concentrations against a wide variety of organisms
Soluble in formulation
Non-toxic
Stable
Pharmaceutical Preservatives:
Alcohols
-Ethanol: Requires greater than 15%, limited to oral products, may be lost due to volatility.
-Benzyl alcohol: Also has a local anesthetic action. Burning taste
– not used orally. Water soluble, stable over wide pH range.
Widely used in parenterals.
-Chlorobutanol: Campor-like -odor and taste – not used orally. Used in parenterals and ophthalmics. Volatile, lost through rubber stoppers and plastic containers.
Pharmaceutical Preservatives:
Acids
- Only active in unionized (lipid-soluble) form.
- Benzoic acid (pKa = 4.2): Used in oral products.
- Sorbic acid (pKa = 4.8): Used in oral products, excellent for molds and yeast.
Pharmaceutical Preservatives:
Esters of p-hydroxybenzoic acid (Parabens)
- Widely used orally. Not ionize but hydrolyze rapidly at pH values above 7. Anesthetize tongue.
- Most lipophilic ones (Propyl paraben and butyl paraben) are best against mold and yeast; less lipophilic ones (methyl paraben and ethyl paraben) are best against bacteria.
- Low solubility is a problem.
- Cause skin sensitization when used in dermatological products.
Pharmaceutical Preservatives:
Quaternary ammonium compounds
- Benzalkonium chloride (Zephirin)
- Cetyltrimethylammonium chloride (Cepryn)
- Widely used in ophthalmics. Very water soluble and fast killing. Incompatibility issues due to positive charge.
Factors affecting preservative action
- pH: Only the unionized species of weak acids are effective as a preservative. Need to add more total weak acid when pH is above pKa in order to have effective concentration of unionized species.
- Complex formation: Only the uncomplexed (free) preservative is active.
- Adsorption by solids: Only the unadsorbed preservative is active.
- Chemical stability: Consider the shelf-life.
