Ceutics Quiz 4 review

advantages of suspensions

mask tastes(drug in particles form not dissolved), ease of swallowing(this is another liquid alternative if solutions can’t be made due to drug insoulbility)

in most good pharmaceutical suspensions the particle diameter is

1-50 mcm

colloidal suspension

if drug particle size is less than 1 mcm

coarse disperson/suspensions

if drug particle size is greater than 1 mcm

sedimentation can cause….

inaccurate dosing

reduced if incomplete sedimentation and dose omission if complete

sedimentation rate and particle size relationship

directly proportional to size of particle

BLANK particle size, BLANK sedimentation rate of suspended particles

higher, faster

characteristics of suspension with large particles

faster sedimentation

easier resuspension (bc its loosely packed)

produce gritty sensation to patients

characteristics of suspension with small particles

slower sedimentation

harder resuspension(forms hard cake when settled)

feel smoother to patient

characteristics of ideal suspenson

easy re-dispersibility

good palpability(not to gritty)

how to achieve a balance between palpability and re-suspension

flocculation

what is flocculation

converting fine smaller particle clump together through WEAK bonds to form loose fluffy aggregates called flocs (not making bigger particles)

how do you make a flocculation

adding flocculating agents

if flocculation is an option to make a drug better would you choose a drug with smaller particle size (Ex 5 mcm) or larger particle size (Ex 40 mcm)

definitely the smaller one to make a floc that has larger particle characteristics

what happens when patients injest flocs

they break down and provide smooth feel

electrolyte flocculating agent example

aluminum chloride, calcium chloride, sodium acetate

polymer flocculating agent example

starch, gelatin, xanthan gum, carbopol

surfactants flocculating agents examples

nonionic and ionic surface-active agents (surfactant)

tween 80, sodium lauryl sulfate

clays as flocculating agents examples

bentonite(colloidal hydrated aluminum silicate)

veegum (magnesium aluminum silicate)

flocs are held together via

weak bonds

what is the advantage of flocs? why not just use larger particle suspension?

they provide smooth feeling as opposed to gritty=better patient acceptance

how do flocs provide smooth sensation

flocs are mostly liquid filled and break apart under slight pressure (like shaking) back into finer particles to be sensed as smooth

one limitation of flocculated suspension

settled particles might not comfort patient and they might not want to take it if it looks “different/bad”

how to fix patient comfortably with sedimentation

increase viscosity to slower sedimentation

sedimentation rate is BLANK to the viscosity of the medium/continuous phase

inversely

BLANK the viscosity of the medium/continuous phase BLANK the sedimentation rate of suspended particles

higher, lower

what is a disadvantage of too high viscosity

the suspension looses ease of pourability, need optimal balance

natural polymer example for viscosity modifers/suspending agents

acacia, tragacanth, xanthan gum, gaur gum

semisynthetic polymer examples for viscosity modifers/suspending agents

methlycellulose(MC), hydroxypropyl cellulose(HPC), hydroxyprorpyl methylcellulose(HPMC), sodium carboxymethylcellulose (NaCMC)

synthetic polymer examples of viscosity modifiers/suspending agents

carbopol (carbomer), polyvinyl alcohol

clay (colloidial silicates) examples as viscosity modifers/suspending agents

bentonite, veegum (magneisum aluminum silicate), Kaolin

other examples of viscosity modifers/suspending agents

silicia, alginates

a properly prepared pharmaceutical suspension should

settle slowly and be readily re-dispersed upon gentle shaking

particle size of suspension should

remain constant throughout long period of undistributed standing

suspension should pour…

readily and evenly from container

packaging and storage for suspensions

widemouth container for pouring and adequate airspace above liquid for shaking

tight containers(protect from excessive heat, freezing and light)

shaken before each use(uniform distribution and accurate dosing)

how can me make hydrophobic drug particles spread evenly throughout the liquid vehicle (water)

add wetting agents

adding hydrophobic drug to water causes

agglomerate and floating of particles on surface as opposed to uniform dispersion

wetting agents help a liquid spread more easily over solid particles by

reducing surface tension between solid and liquid

improve the flow of liquid vehicle across particle surface

3 wetting agents to know

alcohol(also co solvent and microbial preservative), glycerin(preservative effect), propylene glycol

used when aqueous vehicle is to be used as dispersion phase

ready-to-use form

drug already distributed through liquid vehicle

Ex: oral suspension of anticonvulsant drug phenytoin

dry powder form

intended for suspension in liquid vehicles, made before dispensed

Ex: amoxicillin

when would an extemporaneous suspension need to be made and from what

from a soild dosage form(tablet or capusle)

when some patient like infants or elderly don’t have convient acces to liquid dosage forms in medications they need to take

extemporaneous suspension compounding steps

reduce drug to fine powder (mortar and pestle)

add small amount of vehicle (water) to form paste

gradually add more vehicle in portions while mixing

bring to final volume

extemporaneous suspension compounding advantage

easier administration

why is gradual adding of vehicle important

to prevent clumping

amount of water is important, correct final volume leads too

correct drug concentration and dose

too much water leads too

lower drug concentration per dose

too little water leads too

too high of concentration per dose

why purified water even in suspensions?

minimized introduction to impurities or microbes

reconstitute process for dry powder for oral suspension

loosen powder by tapping container against surface

use exact specified water on label

add water in protions and shake appropriately

shake throughly until all powder suspended

ingredients to avoid in neonates

extemporaneous formulation should be as simple as possible

no preservatives, colorants, flavoring agents, alcohol, benzyl alcohol, propylene glycol

some of this aren’t necessary especially if being delivered through a tube into stomach i they can’t swallow

alcohol should generally be avoided in nenonates because it may cause

alter liver function

cause gastric irritation

produce neourlgic depression

products that contain substantial amounts of alcohol like aromatic elixir NF (21-23%) should be avoided in neonates TRUE or FALE

ture

why should benzyl alcohol be avoided in neonatal formulations

been associated with gasping syndrome, which can involve deterioration of multiple organ system and can be fatal

why should propylene glycol be avoided in nenonates

seizures ands tupor in some preterm infants

emulsion

dispersion of two immisicble or partially miscible liquids

in emulsion the droplet are in the BLANK phase and the phase surronding the other is the BLANK phase

dispersed, continuos

how to apply external force in emulsions

mortar and pestle, vortex, sonicator, stirring, homogenizer

what are the 2 types of emulsions

O/W and W/O

O/W emulsions

oil is the dispersed (droplets) and water is the continuous/external phase

W/O

water is the dispersed (droplets) and oil is the continuous/external phase

O/W emulsion preparation

oil is heated until liquified )if heat is required, oil phase may contain multiple lipophilic phases)

oil soluble components dissolve in oil phase and water soluble components are dissolved in the aqueous phase and heated to same temp as oil phase

add oil phase INTO water phase, volume of water is usally higher in O/W emulsions

mixed until cool and made to weight or volume

add the BLANK phase to the BLANK phase

dispersed, continuous

W/O emulsion preparation

oil is heated until liquified )if heat is required, oil phase may contain multiple lipophilic phases)

oil soluble components dissolve in oil phase and water soluble components are dissolved in the aqueous phase and heated to same temp as oil phase

add water phase INTO oil phase, volume of oil is usally higher in W/O emulsions

mixed until cool and made to weight or volume

advantages of emulsions in enhanced palatability

O/W emulsions contain oil droplet in dispersed in an aqueous phase ( drug not good in taste) and the continuos phase covers it to prevent from contacting taste bud

drug is in dispersed phase covered by continous phase

O/W emulsions examples

laxatives(mineral or castor oil)

nutritional supplements(fish liver oils and vegetable oils)

Dispersing the oil in the internal phase helps BLANK, improving patient acceptability for oral administration.

mask its unpleasant taste and reduce odor

oil phase can also BLANK poorly water-soluble drugs and BLANK for oral administration

dissolve, vitamins

why do O/W emulsions cause enhanced palability

lipophilic drugs usually don’t taste good, so covering it with the water phase prevent it from contacting your taste buds

emulsions are similar to what other dosage form based on there deilvery

solutions

solutions and emulsions are both already in a from ready to be absorbed

what type of emulsions is used for delivery of a lipophilic drug

O/W emulsion

enhanced absorption advantage in emulsions

drug already in molecular form

small oil droplets provide BLANK facilitating drug transfer into gastrointestinal fluid for absorption and oral delivery

large interfacial area

in emulsions, the drug is already BLANK in the oil phase, reducing the need for BLANK of solid drug particles

dissolved, dissolution

oral emulsions may improve the BLANK and extent of BLANK compared with suspensions or tablets, depending on formulation and drug

rate, absorption

absorption is faster for droplets that are smaller or larger?

smaller, because surface area is increased

emulsions in IV reduce BLANK and higher BLANK

toxicitiy and drug payload

sterile IV O/W emulsions are used as a source of BLANK and essential BLANK for debilitated patient

calories, fatty acids

example of sterile intravenous O/W emulsions

intralipid

intralipid also used as an intravenous drug BLANK for drug of limited BLANK

provide examples of this

carriers, limited water solubility

Ex: diazepam, propofol, and vitamin

advantage of intravenous emulsion (O/W) over solutions formulations included

higher drug payload(carrys more drug)

lower toxicity

less pain on injection (compared to w/o)

protection of liable drug by the oily environment

for subcutaneous and intramuscular delivery what kind of emulsions can you use

W/O

used for enhanced immunity and antigen delivery in vaccines

W/O emulsions administered by the subcutaneous or intramuscular routes can
be used

to prolong the delivery of water-soluble antigens and thus provide a longer-lasting immunity. (takes time for the water soluble antigen in droplet to travel out through continuous oil phase)
• Because the antigen or drug must first diffuse from the aqueous droplets through the oily external phase before it reaches the tissues (delay antigen response, only want to do this slightly)

why are W/O emulsions difficult to inject

because of high viscosity of oil in continuous phase

emulsions without emulsifying agent (emulsifier) causes

coalescence of small droplets into larger droplets then phase seperation

emulsifying agent is also called

surface-active substance

what do emulsifying agents do

reduce interfacial tensions between two immiscible liquid and form protective film around dispersed droplets

prevent coalescence

allows two immiscble liquids to mix and stay mixed (not a completely mixture just means remains as is when dispensed)

emulsifiers stabilize….

the droplets in the continuous phase

two types of emulsifing agents

synthetic or semisythentic and polymers or naturally occuring

surfactants (surface-active agents)

lowers surface or interfacial tensions between two phases

amphiphilic in nature

associate with both phases

localize at the interface between water and oil

surfactant are termed as BLANK

amphiphiles

how surfactants work

head group towards water phase and tail group to oil phase

surfactant for protective film to prevent BLANK

coalescence( merging of droplets into larger droplets)

anionic surfactant

negative charge in polar/hydrophilic head group

occasionally used

anionic surfactant dissociate at BLANK pH to form long anion with surface activity

high (basic)

anionic surfactant are salt of BLANK

acids, so they ionize at higher pH, We want this

emulsifying properties are lose and emulsions are unstable in BLANK conditions for anionic surfactants

acidic conditions

become unionized in cationic materials

cationic surfactant

positive head group

not commonly used, less biodegradable and toxic

cationic surfactant dissociate at BLANK pH to form long chain with surface activity

low pH (acidic)