Lecture 1 Flashcards
Solution
Homogeneous molecular dispersion
Emulsion
Oil in water, water in oil, looks like bubbles
Suspension
Solid in water or oil, looks like dirt
Solution dosage form examples
Injectables, nasal solutions, opthalmic solutions, otic solutions, irrigation solutions, enemas, douches, gargles, mouthwashes, juices
Advantages of solution dosage forms
Homogeneous no problems of content uniformity, easy to manufacture, good bioavailability
Components of solution dosage forms
Active ingredient = drug
Solvent = water, vegetable oils
Cosolvent = ethanol, glycerin, propylene glycol
Buffering agent
Preservative
Antioxidant, chelating agent
Flavor and sweetener = sucrose, sorbitol
Buffer
Solution of weak acid and salt of its conjugate base
Weak acid removes
added base
Salt removes
added acid
Henderson 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
Van slyke equation
b=2.3C ka[H3O]/Ka+[H3O]^2
C = total buffer concentration
Max when pH=pka
Selection of pH
Use pH that provides maximum stability for drug
Minimize irritation with parenteral, opthalmic, or nasal dosage forms by adjusting to be the same pH of body fluid
pH of blood, interstitial fluid, and tears
7.4
Other ways to minimize buffering capacity besides pH
Minimize volume, administer slowly
Antimicrobial preservative purpose
protect patient from pathogens
maintain potency and stability of dosage forms
Antimicrobial preservative mechanism of action
Preservatives adsorb to bacterial membrane and disrupt it. Bacterial 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
Ampules allowed bacterial content
Must be sterile, single dose, no preservative needed
Multiple dose vial allowed bacterial content
must be sterile, may contain 10 doses, need a preservative to kill microorganisms introduced during use
Opthalmic solution allowed bacterial content
must be sterile, must contain a preservative if packaged in multiple dose container
Oral liquid allowed bacterial content
need not be sterile but should not contain pathogens. FDA limits number of organisms to be less than 100 per mL, need preservative for multiple dose packages
Oral solids allowed bacterial content
Less likely to carry bacterial than liquid forms, test raw materials to be sure 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, acids, esters of p hydroxybenzoic acid (parabens), quaternary ammonium compounds
Alcohols
Ethanol, benzyl alcohol, chlorobutanol
Ethanol
requires greater than 15% limited to oral products, may be lost due to volatility
Benzyl alcohol
Local anaesthetic action, burning taste (not use 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 Opthalmics, volatile, lost through rubber stoppers and plastic containers
Acids
only active in unionized lipid soluble form
benzoic acid
pka 4.3, used in oral products
Sorbic acid
pka 4.8, used in oral products, excellent in molds and yeast
Esters of p-hydroxybenzoic acid (Parabens)
Widely used orally, hydrolyze rapidly at pH values above 7, anesthetize tongue
Low solubility is problem, causes skin sensitization when used in dermatological products
Propyl paraben and butyl paraben
Most lipophilic esters, best against mold and yeast
Methyl paraben and ethyl paraben
Lease lipophilic esters, best against bacteria
Quaternary ammonium compounds
Benzalkonium chloride (zephirin), cetyltrimethylammonium chloride (cepryn), widely used in opthallmics, water soluble and fast killing, incompatibility issues due to positive charge
pH affect on preservative action
Only unionized species of weak acids are effective as preservative, add more total weak acid when pH is above pka to have effective concentration of unionized species
Complex formation effect on preservative action
Only uncomplexed free preservative is active
Adsorption by solids effect on preservative action
only the unadsorbed preservative is active
Chemical stability effect on preservative action
Consider the shelf life
Antioxidants
Drug substances that are less stable in aqueous media than in solid dosage forms, reactions may occur from ingredient-ingredient interactions/container product interactions
Oxidation
Main degradation pathway of pharmaceuticals, initiated by heat, light, peroxides, metals (copper or iron)
Auto-oxidation
automatic reaction with oxygen without drastic external interference
Free radical scavengers
retard, delay oxidation by rapidly reacting with free radicals
Examples of free radical scavengers
Propyl, octyl, dodecyl esters of gallic acid, BHA, BHT, tocopherols, Vitamin E
Reducing agents
Have lower redox potentials than drug, more readily oxidized
Examples of reducing agents
Sodium bisulfite, ascorbic acid, thiols
Chelating agents
Antioxidant synergists, little antioxidant effects, remove trace metals like citric acid, EDTA