Liquid dosage forms - solution Flashcards
What are the types of liquid dosage forms?
Solution: homogeneous molecular dispersion
Emulsion: oil in water or water in oil
Suspension: solid in water or oil
What are the advantages of solutions?
Homogenous (no issues with content uniformity) (any fraction is the same context)
Easy to manufacture
Good bioavailability (already dissolved, able to get into bloodstream or tissue & have effect)
What are two things to know in designing a buffer?
Buffer principle:
A solution of a weak acid and a salt of its conjugate base
Why is a weak acid with a pKa close to the desired pH selected?
use a pH that provides the maximum stability of drug (pH closes to pka)
use a pH that matches the pH of body fluid (blood, interstitial fluid, tears) to minimize the irritation of the IV, eye drop, or nasal drug
Good Solutions
- administer slowly
- minimize buffering capacity
- minimize volume
Examples of Solution Dosage Forms
injectable
nasal solution
opthalmic solution
otic solution
irrigation solution
enemas
douches
gargles
mouthwashes
juice
Disadvantage of Solution
Less stable chemically (contains a small shelf-life)
General Components of Solution
Active Ingredient (drug)
Solvent (water, vegetable oil)
Cosolvent (ethanol, glycerin, propylene
glycol) –> helps dissolve the drug
Buffering Agent –> maintains pH and holds the ionization state
Preservative –> supports the stability of the drug
Antioxidant, Chelating Agent –> supports the stability of the drug
Flavor/Sweetener (sucrose, sorbitol) –> helps with the taste of the drug
Overview of Buffers
Weak Acid removes added base
HA + OH- <—> H20 + A-
the proton from the acid neutralizes the negative charge of the base
Salt removes added acid
A- + H30+ <—-> HA + H20
the negative charge and positive charge react/attract and form a neutralize stabilized form
Buffer Equations
Henderson-Hasselbalch
pH = pka + log (A-)/(HA)
Buffering Capacity –> ability of buffer to resist a change in pH of 1 unit to the added base/acid
B = 2.3 C (ka * H30+)/(ka + H30+)^2
pka= 10^-ka
pH= 10^-(H+)
Antimicrobial Preservation
Purpose
- protect the patient from pathogen
- maintain potency & stability of dosage forms
Mechanism of Action
- preservative absorb to the bacterial membrane and disrupt
- membrane is very lipophilic (hydrophobicity) and has a net negative surface charge allowing for electrostatic interactions
Compounds with Lipid Solubility Actions
alcohol, acid, ester
Compounds with Electrostatic Attraction
quaternary ammonium compound
Bacterial Content
Ampule: sterile, single dose, no preservative
Multiple Dose Vial: sterile, contains up to 10 doses, preservative required to kill microorganisms
Ophthalmic Solution: sterile, preservative required
Oral Liquid: no sterile, no pathogens (less than 100 per mL), preservative required
Oral Solid: less likely to carry bacteria, tests for raw material and facility is clean (LOW CRITERIA)
Ideal Preservatives
effective in low concentrations (potent)
soluble in formulation
non toxic
stable
Pharmaceutical Preservative
alcohol
acid
Ester of p-hydroxybenzoic acid
quaternary ammonium compound
Alcohol
Ethanol: greater than 15%, limited to oral products, lose concentration overtime
Benzyl Alcohol: local anesthetic affect, burning taste (no oral), water soluble, stable over wide pH range
Chlorobutanol: campor-like odor/taste (no oral), volatile
Acids
NO CHARGED ACID –> must be active in unionized (lipid soluble)
Benzoic Acid (pka 4.2): used in oral products
Sorbic Acid (pka 4.8): used in oral products (molds and yeast)
Esters of p-hydroxybenzoic acid
widely used as an oral solution
hydrolyze rapidly at pH above 7
Lipophilic: propyl paraben & butyl paraben (molds/yeast)
Lipophobic: methyl paraben & ethyl paraben (bacteria)
Problems: low solubility and can cause skin sensitization when used dermally
Quaternary Ammonium
Benzalkonium chloride
Cetyltrimethylammonium chloride
used in ophthalmics
water soluble
contains a positive charge –> incompatibility
Factors that Affect Preservative
pH: must be unionized
Complex formation: must be free (uncomplexed) to be active
Absorption by solids: must be unabsorbed to be active
Chemical Stability: good shelf life
Antioxidants
drug substances are less stable in aqueous media than solid forms
Oxidation
main degradation pathway of drugs (vitamin, essential oils, fats, oils)
initiated by heat, light, peroxides, metals (copper & iron)
Free-Radical Scavengers
retard, delay oxidation by rapidly reacting with free radicals
propyl
octyl
dodecyl esters
BHA
BHT
tocopherols
Vitamin E
Reducing Agents
have lower redox potentials than drug –> readily oxidized
Sodium Bisulfite
Ascorbic Acid
Thiol
Chelating Agents
contain antioxidant synergists
remove trace metals
Citric Acid
EDTA
