E 1 L 1 - Liquid Flashcards
Solution
Homogenous molecular dispersion
Emulsion
Oil in water/water in oil
Suspension
Solid in water or oil
Examples of solution
Injectables
Nasal Solutions
Ophthalmic solutions
Otic solutions
Irrigation solutions
Enemas
Douches
Gargles
Mouthwashes
Juices
Advantages of Solution dosage forms
**Homogenous - no problems of content uniformity
-Easy to manufacture
-Good Bioavailability
Components of solution dosage forms
-Active drug (drug)
-Solvent (water/veg, oils, for Long-acting parenteral)
-Co-solvent (ethanol, glycerin, propylene glycol)
-Buffering agent
-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
-Salt removes added acid
Common pharmaceutical buffers
Citric Acid
Glycine
Phosphoric acid
Antimicrobial Preservatives purpose
-Protect patient from pathogens
-Maintain potency and stability of dosage forms
Antimicrobial Preservatives mechanism of action
Preservatives adsorb 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 interaction (ex. quart. amines)
Bacterial content allowed in: ampules
Must be sterile, single dose, no preservative needed
Bacterial content allowed in: Multi 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 to 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: 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
Pharm 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 ophthalmic. Volatile, lost through rubber stoppers and plastic containers.
Pharm 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
Pharm 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
Pharm Preservatives: Quaternary ammonium compunds:
-Benzalkonium Chloride (Zephirin)
-Cetyltrimethylammonium chloride (Cepryn)
-Widely used in ophthalmic. 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
Antioxidants
Drug substances are less stable in aqueous media than solid dosage forms
-acid-base reactions, acid base catalysis, oxidation, or reduction may occur from ingredient-ingredient interactions or container-product interactions
Antioxidants: Oxidation
-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 ion-> free radicals react-> react with oxygen->more free radicals
Antioxidants: Free-radical scavengers
Retard, delay oxidation by rapidly reaction 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 -> 2NaHSO4
-Ascorbic acid
-Thiols
Antioxidants: Chelating agents
-Antioxidant synergists
-Little antioxidant effect themselves
-Remove trace metals
(citric acid; EDTA)
Chelating agents
EDTA and Citrate
pH =
pka + log [A-]/[HA]
How to find pKa from Ka
-log(ka)
How to do pH when value added
subtract new value from acid, and add new value to conj. salt, and then do pH as normal
c =
acid + salt
