Exam 3 Flashcards
liquid dosage forms that only contain one phase
monophasic
liquid dosage forms that have dispersion
biphasic
coarse vs colloidal
types of dispersions
classification of liquid dosage forms - ready to use liquids
solutions, suspensions, emulsions
classification of liquid dosage forms - powders for reconstitution
chemically unstable drugs, solution or suspension, oral, topical, injectable
injectable, ophthalmic, some nebulized liquids, vehicles (SW, NS, etc.)
sterile liquid dosage forms
we must ensure a low bioburden by proper procedures during manufacture, storage, distribution, dispensing (classification of liquid dosage forms)
non-sterile
easier to swallow than solids (pediatric, geriatric, dysphagia), faster absorption rate, easier to adjust the dose (can be diluted, compounded), liquids are best dosage form for some routes (IV) or for some drugs
advantages of liquid dosage forms
increased chemical instability, prone to microbial contamination, inconvenient and bulky, taste issues, less accurate dosing, leakage/loss, too rapid absorption, controlled release difficult to achieve
limitations of liquid dosage forms
solvents/cosolvents, solubilizers, preservatives, sweeteners, surfactants, suspending agents, antioxidants, flavoring agents, buffering agents
excipients for liquid dosage forms
to inhibit the growth of microorganisms that might be introduced from repeatedly drawing doses (sterile), to protect from microbiological growth (non-sterile)
why preserve a product
activity against various microorganisms, safety, pKa of preservative, pH of product, solubility of preservative, stability of preservative, suppliers/cost/regulatory limits
preservative considerations
physiologically compatible, maintain stability, improve solubility
pH of liquids
routes of administration, volume of product (small vs large), way of administration (infusion or bolus injection), buffered or unbuffered, occasional dosing or repeated use
acceptable pH ranges depends on these things
pH of formulation, presence of micelles, presence of hydrophilic polymers
factors affecting preservative efficacy in solutions
_________ is a preservative that is affected by the pH of the formulation
benzoic acid because it is ionized acid
if the pH is higher than the pKa more of the acid will be in the ionized form thus potentially rendering the preservative ineffective, when the preservative is ionized it is soluble in water so it won’t have antimicrobial activity because it essentially just goes away, need to have some unionized preservative to be effective, benzoic acid only effective at pH lower than 4
preservative-pH relationship
something surrounded by phospholipids
micelles
free concentration of preservative in solution is reduced in the presence of hydrophilic polymers due to chemical interaction, preservative may be incompatible with hydrophilic polymers in formulation due to electrostatic interaction (cationic hydrophilic polymers should not be used in conjunction with acidic preservatives)
presence of hydrophilic polymers
faster onset of activity (no rate limiting dissolution process), good for children and elderly (easy to swallow), homogenous/always uniform unlike suspensions and emulsions, flexible dosing (dose titration), given by many routes of administration (including IV infusion)
advantages of solutions
expensive to ship and bulky for patient to carry, leakage from container, unsuitable for therapeutic agents that are chemically unstable in the presence of water (less stability that solids), poor solubility of certain therapeutic agents may prohibit their formulation as solutions, more pronounced taste
disadvantages of solutions
oral, topical (dermal, ophthalmic, nasal, otic, inhalants, enemas/douches), parenteral
types of solutions
homogenous mixtures of solutes dissolved in solvents
solutions
aqueous solutions containing a high concentration of sugar or sugar substitute with or without medicinal substances
syrups
sweetened hydroalcoholic solutions, ethanol
elixirs
solutions of aromatic materials in alcohol, commonly used as flavoring agents or inhalation for syncope (respiratory stimulant, ammonia)
spirits
solutions of aromatic materials in water
aromatic waters
alcoholic solutions prepared by extracting active constituents from crude drugs
tinctures
solutions (or suspensions, emulsions) intended for external application to the skin (need not be rubbed forcefully)
lotions
liquid preparations intended to be rubbed with friction and massaged onto unbroken skin (more viscous than lotions)
liniments
solutions of pyroxylin in ether and alcohol that are intended to be painted onto the skin and left to dry (forms a protective film)
collodions
aqueous or oily based solutions in the form of droplets to be applied topically to the nasopharyngeal tract/skin
sprays
solutions introduced to the rectum to empty the bowel
enema
administered to a body cavity (vagina) to disinfect or remove debris
douches
solutions designed to wash the bladder, eyes, or open wounds
irrigations
designed to cleanse a part of the body
washes
designed to treat diseases that impact the throat
gargles
sterile solutions that can be administered subcutaneously, intramuscularly, or intravenously
injections
solvents, pH adjusting agent or buffer, solubility improving agents, stability improving agents, preservatives, colors, flavors, sweeteners, tonicity agents
solution excipients
nature and composition of solvent medium (polarity, pH, buffer), nature of API (chemical and physical properties), solubilizing and dissolution process
factors affect solubility of therapeutic agents
optimization of pH of formulation, solubilization using cosolvents, use of non-aqueous as a solvent, add a solubilizing agent (surfactant, complexing agent), change the chemical structure of the drug (appropriate selection of drug form/salt, complex)
formulation methods to enhance/optimize the solubility of therapeutic agents
ethanol, propylene glycol, isopropyl alcohol, glycerin (glycerol), low MW PEGs
common cosolvents
dispersed system with insoluble solid particles, some of the drug does dissolve in the medium to the extent of solubility (degradation of the API), dispersion medium (aqueous, non-aqueous, oils)
suspensions
uniform dispersion, sediment slowly and resuspend easily upon shaking, no significant particle growth through shelf life, desirable flow properties, should be acceptable to patient (appearance, color, flavor, grittiness, taste)
requirements of suspensions
administering a poorly water-soluble drug in liquid form compared to solids (easier to swallow, dose easier to adjust), better chemical stability and longer shelf life compared to solutions (bad taste easier to mask, higher dose possible)
advantages of suspensions
physical stability problems (heterogeneous systems and will sediment/cake), shelf life may be limited by chemical stability (drugs are more prone to chemical instability compared to solids), dosing accuracy (measuring inaccuracy, lack of uniformity), not as portable and convenient as solids
disadvantages of suspensions
wetting agents, suspending agents, flocculating agents
excipients in suspensions
random movement in all directions, rate of diffusion is inversely proportional to particle diameter
brownian motion
net charge at the outer boundary of the double layer of a particle
zeta potential
encourage suspended particles to form loose flocs of low density, flocs will sediment faster than primary particles, neutralize the zeta potential by adding excipients, polymers to form bridges to promote this
controlled flocculation
any electrolytes that carry a charge opposite to that of the zeta potential of the suspended particles
flocculating agents
particles in _________ must dissolve before absorption
suspension
oil/water, increased bioavailability of lipophilic drugs, oil soluble/oily drug
oral emulsions
creams (o/w or w/o), semisolids, lotions, non-medicated or medicated
dermal emulsions
oil/water, intravenous lipid emulsions (IVLE), 0.1-0.5 micrometers
parenteral emulsions
surfactants (tweens, spans), particulate colloid emulsifiers (fine particles, bentonite, veegum, magnesium, aluminum hydroxide), polymers (pectin, lecithin, cellulose derivatives)
emulsifying agents
glycerol, PEG, carbomer
viscosity enhancers for emulsions
o/w or w/o emulsions
macroemulsions
o/w/o or w/o/w, sustained release dosage forms
multiple emulsions
clear, thermodynamically stable emulsions
microemulsions
water is the dispersion medium and oil is the dispersed phase, high HLB value, preferred for internal use, used externally as vanishing cream, non-greasy and easily removable from the skin
o/w emulsions
oil is the dispersion medium, low HLB value, preferred for external use (lotions, creams, moisturize and treat skin conditions), greasy and oily, used externally to prevent evaporation of moisture
w/o emulsions
make it viscous (semisolid emulsion, no/slow sedimentation/creaming, shaking not needed), make it colloidal emulsion (microemulsions), minimize/delay flocculation and coalescence (increase zeta potential, emulsifying agents)
improving physical stability of emulsions
API degradation, oils and lipids in emulsions are susceptible to oxidation or enzymatic hydrolysis (rancidity - unpleasant odors/flavors), hydrolysis of triglycerides releases free fatty acids which lowers the pH of the emulsion and changes the zeta potential, commonly used excipients to improve stability are antioxidants and chelating agents
chemical stability of emulsions
emulsions need antimicrobial preservatives, emulsions contain water, natural oils and emulsifiers are good media for microorganisms to grow, microbial enzymes can degrade oil, emulsifier, causes rancidity, discoloration, change pH, breakage of emulsion
microbiological stability of emulsions
aqueous solutions used to treat or prevent infections (topical antibiotics), pleasant taste/odor, can be available in concentrated forms with directions for dilution or used undiluted, maintain contact with mucous membrane
oral rinse, gargle, mouthwash
viscous liquid preparations used for mouth and throat infections, glycerin common base (adheres to mucous membrane for long period, possesses a sweet taste)
throat paints
small volume to prevent spillage, concentration is used to adjust a dose instead of increasing volume, non-irritating, isotonic, viscous, sterile, preserved if necessary
ophthalmic liquids
solutions, suspensions, oily liquids, sterile, preserved, isotonic, more volume than eyes
otic liquids
rapid onset of action comparable to IV, ease of delivery (painless, non-invasive, needle-free, self-medication), improve bioavailability by bypassing GI and liver first pass metabolism, lower dose so less ADR
nasal drops/sprays
rectal liquid (solution or suspension), administered/injected into the rectum, may be administered for cleansing/evacuation effect or provide local drug effect
rectal enema
aerosol/inhalation (nebulizers, MDIs), instillation/endotracheal administration (tracheal tube - catheter, surfactant delivered to premature infants)
pulmonary drug delivery
3-in-1 or total nutrient admixture (TNA - dextrose, amino acids, IV fat emulsion) or dextrose and amino acids (2-in-1) with separate fats infusion
parenteral nutrition (PN)
