Liquid Dosage Forms Flashcards
Definition
Solution
Homogeneous molecular dispersion
Definition
Emulsion
oil in water/water in oil
Definition
Suspension
solid in water or oil
Advantages of Solution dosage forms
- homogeneous - no problems of content uniformity
- easy to manufacture
- good bioavailability
Components of Solution
- active ingredient (drug)
- solvent
- buffering agent
- preservative
- antioxidant, chelating agent
- flavor and sweetener
Solvents used for long-acting parenterals
water, vegetable oils
Co-solvet examples
- ethanol
- glycerin
- propylene glycol
Flavor and sweetener examples
sucrose and soritol
Buffer principle
a solution of a weak base and a salt of its conjugate base
Buffer equation for a weak acid removing added base (OH-):
HA + OH- ⇿ H2O + A-
Buffer equation for salt removing added acid (H+)
A- + H3O+ ⇿ HA + H2O
Handersen-Hasselbalch equation
Definition
Buffer capacity
Ability of a buffer to resist a change in pH due to added OH- or H+. Amount of strong acid or base needed to change pH by one unit.
Buffer capacity equation: 1
Buffer capacity equation: 2
(Van Slyke)
C = total buffer [ ] = [HA] + [A-]
T or F: Buffer is at max capacity where pH=pKa
True
Common pharmaceutical buffers
- acetic acid
- citric acid
- glycine
- phosphoric acid
what is this structure?
acetic acid
what is this structure?
citric acid
monobasic, dibasic, and tribasic
what is this structure?
glycine
what is this structure?
phosphoric acid
monobasic, dibasic, and tribasic
We want to select a pH that provides ___ ___ for the drug. If possible, we want the pH to match the pH of the ___.
maximum stability, body
When pH is selected we want to:
* ___ the buffering capacity
* ___ volume
* administer ___
minimize, minimize, slowly
Buffer Preparation - Exercise 1
A buffer contains 0.1 M sodium formate and 0.1 M formic acid. 0.03 M of sodium hydroxide was added. The Ka of formic acid is 1.77 x 10 -4
(pKa = -log(Ka) = 3.75).
1. What is the initial pH of the buffer?
2. What is the buffer capacity?
3. What is the pH after the addition of sodium hydroxide?
- 3.75
- 0.115 M
- 4.02
Buffer Preparation – Exercise 2
Design a buffer for a penicillin solution that is most stable at pH 6.5. A buffer capacity of 0.15M is required.
- HA (dibasic citrate) 0.117M
- A- (tribasic citrate) 0.147M
Antimicrobial Preservatives Mechanism of Action
Preservatives adsorb into the bacterial membrane and disrupt it. The membrane is lipophilic and has a net negative surface charge.
Antimicrobial preservatives - 2 methods of adsorption
lipid solubility
* alcohols, acids, esters
Electrostatic attraction
* quaternary ammonium compounds
Bacterial content allowed in various dosage forms
Ampules
must be sterile, single dose no preservative needed
Bacterial content allowed in various dosage forms
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 various dosage forms
ophthalmic solutions
must be sterile, must contain a preservative if packaged in multiple dose container
Bacterial content allowed in various dosage forms
oral liquids
need not to be sterile but should not contain pathogens. FDA limits the number of organisms to be less than 100/mL. Need preservative for multiple dose packages.
Bacterial content allowed in various dosage forms
oral solids
less likely to carry bacteria than liquid forms. Pathogen contamination is still a concern. Test raw materials and be sure that the manufacturing facility is clean.
Characteristics of ideal preservatives
- effective in low [ ] against a wide variety of organisms
- soluble in formulation
- non toxic
- stable
Pharmaceutical preservatives
Alcohols
* ethanol: requires more than ___%, limited to oral products, may be lost due to ___
* ___: anesthetic action, burning taste (not used ___). Water ___, stable over wide pH range. Used for parenterals
* ___: campor-like odor and taste (not used orally). Used in ___ and ___. ___, lost through rubber stoppers and plastic containers.
- 15%, volatility
- benzyl, orally, soluble
- chlorobutanol, parenterals, ophthalmics, volatile
Pharmaceutical preservatives
Acids
* benzoic acid (pKa = ___): used in ___ products
* sorbic acid (pKa = ___): used in ___ products, excellent for ___ and ___
- pKa = 4.2, oral
- pKa = 4.8, oral, molds and yeast
only active in unionized (lipid-soluble) form
T or F: acid preservatives are only active in unionized (lipid soluble) form.
True
Pharmaceutical preservatives
Esters of p-hydroxybenzoic acid (Parabens)
* Used ___. Not ___ but ___ rapidly at pH values above ___.
* Anesthetize ___
* Most lipophilic ones (___ paraben and ___ paraben) are best against ___ and ___.
* Less lipophilic ones (___ paraben and ___ paraben) are best against ___.
* low ___ is a problem
* cause skin ___ when used in dermatological products
- orally, ionized, hydrolyzed, 7
- tongue
- Propyl, butyl, mold, yeast
- methyl, ethyl, bacteria
- solubility
- sensitization
Pharmaceutical preservatives
Quaternary ammonium compounds
* Benzalkonium chloride (___)
* Cetyltrimethylammonium ___ (Cepryn)
* Widely used in ___. Very water ___ and ___ killing.
* Incompatibility issues due to ___ charge
* Interacts with negatively charged membrane
- Zephirin
- Chloride
- ophthalmics, soluble, fast
- positive
What is this molecule an example of?
Esters of p-hydroxybenzoic acid (Parabens)
preservative
What is this molecule and what is it an example of?
Benzalkonium chloride (Zephirin), Quaternary ammonium compounds
preservative
What is this molecule and what is it an example of?
Cetyltrimethylammonium (Cepryn)
preservative
Factors affecting preservative action
- pH - only the ___ species of ___ acids are effective as a preservative. Need to add more total __ acid when pH is ___ pKa in order to have effective [ ] of unionized species.
- complex formation - only the ___ preservative is active.
- adsorption by solids - only the ___ preservative is active.
- chemical stability - consider the ___.
- unionized, weak, weak, above
- free (uncomplexed)
- unadsorbed
- shelf-life
Antioxidants
- drug substances are __ stable in aq media than in solid dosage forms.
- acid-base reactions, catalysis, oxidation, or reduction may occur from ingredient-ingredient interactions or ___-product interactions
- less
- container
Antioxidants
Oxidation
* main ___ pathway of pharmaceuticals (vitamin, essential oils, fats, and oils)
* ___- automatic reaction with oxygen without drastic external interference
* initiated by ___, light, ___, metals (Cu and __)
- degradation
- auto-oxidation
- heat, peroxide, Fe
Antioxidants
Free-radical scavengers
* slow/delay oxidation by rapidly reacting with free radicals
* propyl, _, dodecyl esters of acid
* butylated hydroxyanisole (…); butylated hydroxytoluene (…)
* tocopherols; vitamin __
- octyl, gallic
- BHA, BHT
- E
Antioxidants
Reducing agents
* have __ redox potentials than drug; more readily ___
* sodium ___: 2NaHSO3 + O2 → 2NaHSO4
* ascorbic acid
* thiols
- lower, oxidized
- bisulfite
Antioxidants
Chelating agents
* antioxidant ___
* little antioxidant effect themselves
* remove trace metals
* examples: ___ acid and ___
- synergists
- citric, EDTA
Sodium bisulfite is a…
antioxidant acting by preferntial oxidation
EDTA is a…
Chelating agent and antioxidant
butylated hydroxytoluene (BHT) is a …
free radical stabilizer
sorbitol is a…
sweetener
glycerin is a…
co-solvent
methylparaben is a…
preservative acting by lipophilic absorption
benzalkonium chloride is a…
preservative acting by electrostatic adsorption
ascorbic acid is a…
antioxidant and buffering agent
weak acid
benzoic acid is a…
preservative (when unionized/protonated)
chlorpromazine is an…
active ingredient
citric acid is a…
chelating agent, buffering agent, and antioxidant
propylene glycol is a…
co-solvent
sodium dihydrogen citrate is a…
chelating agent, buffering agent, and antioxidant
sucrose is a…
sweetener
water is a..
solvent
