lecture 1 Flashcards
solution
homogeneous molecular dispersion
emulsion
oil in water or water in oil
suspension
solid in water or oil
advantages of solution dosage forms
-homogeneous: no problem of 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, vegetable oil (for long acting parenteral)
-co solvents (ethanol, glycerin, propylene glycol)
T/F the buffer principle is when a solution of a strong acid and a salt of it conjugate base
false it is a weak acid
weak acid removes
added base (OH-)
HA + OH- <——> H2O + A-
salt removes
added acid (H+)
A- + H3O+ <——–> HA H2O
handersen-hasselbalch equation
pH= pKa + log ([A-]/[HA])
buffering capacity
-ability of a buffer to resist a change in pH due to added OH- or H+
-B= (change of acid or base added)/ (change of pH)
-max when pH= pKa
van slyke equation
b= 2.3C (Ka[H3O+])/(Ka + [H3O+])^2
what are the two common pharmaceutical buffers
citrate buffers and phosphate buffers
what is the purpose of antimicrobial preservatives
-protect patient from pathogens
-maintain potency and stability of dosage forms
what are the mechanism of action of antimicrobial preservatives
-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 ampules
Must be sterile, single dose, no preservative needed
bacterial content allowed in 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 ophthalmic solutions
Must be sterile, must contain a preservative if packaged in multiple dose container
bacterial content allowed in 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.
ideal preservatives
-Effective in low concentrations against a wide variety of
organisms
-Soluble in formulation
-Non-toxic
-Stable
bacterial content allowed in 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.
pharmaceutical preservatives in alcohol
-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 presevatives 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
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
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
antioxidants
-Drug substances are less stable in aqueous media than solid dosage forms.
*Acid-base reactions, acid or base catalysis, oxidation, or reduction may occur from ingredient-ingredient interactions or container-product interactions
antioxidant oxidation
-Main degradation pathway of pharmaceuticals
◦ Vitamins, essential oils, fats, and oils
-Auto-oxidation (automatic reaction with oxygen without drastic external interference)
-Initiated by heat, light, peroxides, metals (copper or iron) à free radicals à react with oxygen à more free radicals.
antioxidant free-radical scavengers
Retard, delay oxidation by rapidly reacting with free radicals
* Propyl, octyl, dodecyl esters of gallic acid
* Butylated hydroxyanisole (BHA); Butylated hydroxytoluene (BHT)
* Tocopherols; Vitamin E
antioxidants reducing agents
Have lower redox potentials than drug; more readily oxidized.
* Sodium bisulfite: 2NaHSO3 + O2 à 2NaHSO 4
* Ascorbic acid
* Thiols
antioxidants chelating agents
-Antioxidant synergists
-Little antioxidant effect themselves
-Remove trace metals
* Citric acid; EDTA (Ethylenediaminetetraacetic acid)