Liquid Dosage Forms Flashcards
liquid dosage forms
-solution (homogenous molecular dispersion)
-emulsion (oil in water)
-suspension (solid in water or oil)
Solution dosage form examples
-injectables
-nasal, opthalmic, otic, irrigation solutions
-enemas
-douches
-gargles
-juices
Advantages of solution dosage forms
-homogenous (content uniformity)
-easy to manufacture
-good bioavailability
Components of solution dosage forms
-active ingredient
-solvent
-buffering agent
-preservative
-antioxidant, chelating agent
-flavor and sweetener
Solvent
-water, oils (for long-acting)
-co solvent (ethanol, glycerin)
Buffer principle
-solution of WEAK Acid and salt of CONjugate Base
-weak acid removes added base (OH-)
HA + OH- <–> H2O + A-
-salt removes added acid (H+)
A- + H3O+ <–>. HA + H2O
Henderson Hasselbach
pH = pKa + log[A-/HA]
Buffering capacity
-ability of a buffer to resist a change in pH due to added OH- or H+
-Van Slyke equation
-max when pH = pKa
van slyke equation
B = (acid or base added/pH)
B = 2.3 C (Ka[H3O+]/((Ka+[H3O+])^2)
-C= total buffer concentration = [HA] + [A-]
-max when pH = pKa
Common pharmaceutical buffers
-citric acid
-phosphoric acid
-also glycine and acetic acid
Citrate buffers
-
Phosphate buffers
Selection of pH
-use pH that provides maximum stability for drug
-minimize irritation by adjusting pH to be same as pH of body fluid 7.4
If you cannot match pH of body fluid,
-minimize buffering capacity
-minimize volume
-administer slowly
Antimicrobial preservatives purpose
-protect patient from pathogens
-maintain potency and stability of dosage forms
Antimicrobial preservatives mechanism of action
-absorb and disrupt bacterial membrane
-via lipid solubility or electrostatic attraction
bacterial membrane
-lipophillic
-negative surface charge
Adsorption due to lipid solubility (antimicrobial preservatives)
-alcohols
-acids
-esters
adsorption due to electrostatic attraction (antimicrobial preservatives)
quarternary ammonium compounds
bacterial content allowed in dosage forms
-ampules (sterile)
-multiple dose vials (sterile)
-ophthalmic solutions (sterile)
-oral liquids
-oral solids
Ampules
-must be sterile
-single dose
-no preservative needed
Multiple dose vials
-must be sterile
-up to 10 doses
-NEED preservative to kill microorganisms
Ophthalmic solutions
-must be sterile
-preservative if packaged as multiple dose use
Oral liquids
-not sterile but no pathogens
-e. coli <100 per ml
-need preservative
oral solids
-less likely to carry bacteria than liquids
-test raw materials
-clean manufacturing facility
Ideal preservatives
-effective in low concentrations against a wide variety of organisms
-soluble in formulation
-non-toxic
-stable
Pharmaceutical preservatives
-alcohols
-acids
-esters
-quarternary ammonium compounds
Alcohols
-ethanol
-benzyl alcohol
-chlorobutanol
ethanol
-requires more than 15%
-limited to oral
-may be lost due to volatility
Benzyl alcohol
-local anesthetic action
-burning taste–not used orally
-water soluble
-stable over wide pH range
-used in parenterals
Chlorobutanol
-campor-like odor and taste
-not used orally
-parenterals and ophtalmics
-volatile, lost through rubber and plastic
Acids
-only active in unionized (lipid-soluble) form
-benzoic acid (oral)pka4.2
-sorbic acid (oral, good for mold and yeast) pka4.8
Esters of P-hydroxybenzoic acid (parabens)
-widely used orally
-not ionize but hydrolyze rapidly at pH values above 7
-anesthetize tongue
-lipophilic ones good for mold and yeast
-less lipophilic ones good for bacteria
-low solubility is a problem
-cause skin sensitizatin when used dermatologically
Quarternary ammonium compounds
-benzalkonium chlorise (Zephirin)
-Cetyltrimethylammonium chloride (Cepryn)
-ophthalmics
-water soluble
-fast killing
-incompatibility issues bc positive charge
Factors affecting preservative action
-pH
-complex formation
-adsorption by solids
-chemical stability
pH
-only unionized species of weak acids are effective as a preservative
-need to add more tatal 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
shelf-life
Drug substances are less stable
-in aqueous media than solid dosage forms
-acid-base reactions, catalysis, oxidation, reduction may occur from container-product interactions
Oxidation
-main degradation pathway of pharmaceuticals
-vitamins, fats
-auto-oxidation
-initiated by heat, light, peroxides, metals (cooper or ion)
-free radicals –> react with oxygen –> more free radicals
auto-oxidation
-automatic reaction with oxygen without drastic external interference
Antioxidants
-free-radical scavengers
-reducing agents
-chelating agents
free-radical scavengers
-delay oxidation by rapidly reacting with free radicals
-gallic acid, BHT, BHA, Tocopherols, Vit E
Reducing agents
-lower redox potentials than drug =. more readily oxidized
-sodium bisulfate: 2NaHSO3 + O2 –> 2NaHSO4
-ascorbic acid
-thiols
chelating agents
-antioxidant synergists
-little antioxidant effect themselves
-remove trace metals
-citric acid, EDTA
MAthcing
matching
Ka=
-log(pKa)
[H3O+] =
-log(pH)
