Exam 3 Flashcards
what is a gel
semi solid dosage form
what does a gel consist of structure wise
a matrix formed by hydrogen bonds between..
- gel base/ gel base
- gel base/ active ingredient
- micelle/ micelle
- viscosity primarily due to hydrogen bonds not molecular weight
Can the organic matrix be altered? if so, by what
- temporarily by heat
2. permanently by alcohol
purpose of gels
- vehicle for topical, transdermal, IM or oral preparations
2. achieve high viscosity with low molecular weights
gel solubility
what should it be able to do
what is the exception
must be soluble in body fluids or able to melt @ body temp.
exception: hemostatic gelatin
examples of internal used gel
Amphojel tab/capsule
example of vaginal gel
metrogel (metronidazole)
examples of topical gels
hemostatic gelatin
americaine/ hurricaine (benzocaine)
campho-phenique (camphor/ phenol)
erygel (erythromycin)
examples of transdermal gels
clonidine, gabapentin, ketamine, lidocaine
indomethacin
prochlorperazine
scopolamine
examples of gels used topically for local effect
ketoprofen (PLO)
Transdermal gel dosing
should have what
should have.. 1. specific dose 2. by volume (mg/mL) 3. metering device 4. instructions should read .... ex: apply 1 mL to chest did orrr apply contents of1 syringe bid 5. CAREGIVER SHOULD WEAR GLOVES
Considerations for gel preparations
non organic based gels
- order of incorporation
2. topical
Considerations for gel preparations
organic based gels
- order of incorporation (lipo/hydro phase)
- shear forces
- micelles
- transdermal
(googled)
what is a PLO gel
Pluronic lecithin organogels (PLO gels) are lecithin-based organogels widely used in compounding pharmacies as a vehicle for enhancing the transdermal permeability of many therapeutic drugs.
when rx says to make PLO gel, what ingredients must you use
- drug prescribed (ofc.)
- Pluronic F127 (gel)
- Lecithin/ Isopropyl palmitate solution (oil/solution)
UBSOP policy for compounding transdermal gels
when compounding semi solid UNIT DOSE preparations, 1 extra dose of compound may be prepared
volume of deadspace in syringes for transdermal preparations we have to account for
- 0.1 mL x2 for the headspace of the syringes
- 0.1 mL of headspace in the syringe-to-syringe adapter
0.1+0.1+0.1=0.3
how to determine volume of Lecithin/ Isopropyl palmitate Solution to use when compounding transdermal gels
22% w/v
how to determine volume of plutonic F127 gel to be used when compounding transdermal gels
it is the qs media.
once mixing drug with the lecithin/ isopropyl palmitate solution. expel remaining air and note volume. subtract from total volume to DISPENSE, NOT total volume to prepare (which includes the deadspace volume
will end up with f127 volume needed to compound.
notes from transdermal gel compounding calculations
- calculate total volume to prepare ): prescribed volume + 1 extra +deadpsace volume
- calculate how many doses to prepare: total volume to prepare in proportion to 1mL/dose
- calculate drug amount
- calculate lecithin/ isopropyl palmitate solution: 22% w/v
- calculate F127 volume by subtracting volume of drug/ lecithin mix from TOTAL VOLUME TO DISPENSE (NOT PREPARED).
how to ensure tip contents transferred to main body of an ampule
- gentle tapping against work surface
- swirling
- gentle finger snap
how to safely handle ampule when using one
- ensure tip contents transferred to main body
- swab neck with alcohol swab
- wrap neck with alcohol swab or gauze pad when breaking
- use filter star or filter needle to withdraw
either pre filter or post filter
needles to use when using ampules
use a 0.5 micron filter needle when drawing liquid from ampule. then use switch needle to ensure filtered stuff doesn’t get back into the IV bag
pros and cons of ampules
pros: do not require preservatives
cons: contamination by glass shards upon opening, filtration required
define ophthalmic preparations
USP definition
essentially free from foreign particles, suitably compounded and packaged for installation into the eye (and ocular tissue surrounding the eye)
note: USP 797 “pharmaceutical compounding-sterile preparations” mentions ophthalmic preparations should be sterile
“…which include but are not limited to… inhalations, injections, powers for injection, irrigations, metered sprays, and ophthalmic and otic preparations”
purpose of ophthalmic preparations
administration of medication to the eye
lubrication
cleansing
local vs systemic effect of opthalmic preparations
local effect only? yes
systemic absorption:
always undesired
GI coupling: gets absorbed into nasolacrimal gland
epithelial absorption
capacity of the eye for ophthalmic preparations
1 gtt/ eye
50 mg/ eye (for ophthalmic ung.)
administration of opthalmic medication
1-2 drops (liquid)
1/4”-1/2” (semisolid)
ophthalmic preparaion dosage forms
- solution (aq.)
ex: atropine 1% w/v - ointments: white petrolatum or mineral oil
ex: tetracycline HCL 3% w/v - suspensions: suspending agets
ex: prednisolone 1% (Pred Forte) - Gels
ex: timolol 0.25-0.5% (timoptic XE)
* a solution which forms a gel upon administration
special considerations for opthalmic preparations
- PH: 7.4 (IDEAL)
- tonicity: ~277 mmol-isotonic (ideal)
3: sterility? YES! USP 797 - preservation: maybe
A. tolerable range for pH of opthalmic preparations
B. what happens if not in tolerable range
A .6.5-8.5
pH of 7.4 is ideal, but optimum pH is not always attainable due to concerns of drug stability.
discomfort/ stinging
colligative property that tonicity dictates
also note about colligative properties
osmotic pressure
freezing point depression
boiling point elevation
vapor pressure
*note: colligative properties depend only upon the number of solute particles in solution, not the size of the particles
freezing point
the temperature at which a liquid freezes
freezing point depression
the number of centigrade degrees below the freezing point of water (0 C) at which a liquid freezes
freezing point depression example
what is the freezing point of a solution containing 700 g dextrose QS’d to a final volume of 1000mL
- convert mass to moles using MW
700g/ (180g/mol)=3.888 moles
3.888 mol x 1.86 C/mol=7.23 C degrees.
then that would mean the freezing point of this solution is -7.23 degrees C
NOTE: for water: freezing point is depressed 1.86 centigrade degrees for every mole of particle per liter of solution,
another freezing point depression example
what is the freezing point depression of 5% w/v of dextrose in water
(5g/100 mL)=(Xg/1000mL)
X=50 g
(50g/Xmol)= (180 g/mol)
X= 0.278 mol
0.278 mol (1.86c degrees/mol)=0.517 centigrade degrees (freezing point depression
freezing point =-0.52 degrees centigrade
even though the optimal tonicity for ophthalmic preparations is 277 mM, why may hyper/hypo tonicity be unavoidable
drug stability issues
therapeutic dosing concerns
tolerable tonicity range :
may cause what
200-600 mM
may cause:
discomfort, stinging
TISSUE DAMAGE
Dextrose 5% w/v is isotonic.
show the math to prove it
5g/100mL=X/1000mL
X=50g
50g/Xmol=180.16 g/mol
X=0.277 mols or 277 mM
277mM is isotonic. checks out just fine
problems with calculating tonicity traditionally with ionic solutions
must use I Value (dissociation factor) when calculating
I values for
non electrolytes 2-ion electrolytes 3-ion electrolytes 4--ion electrolytes 5-ion electrolytes
exception
non electrolytes: 1.0 2-ion electrolytes: 1.8 3-ion electrolytes: 2.6 4--ion electrolytes: 3.4 5-ion electrolytes: 4.2 and so forth
exception (zinc sulfate =: I=1.4 (not expected 1.8)
how to find tonicity of ionic compound
ex:
find the moles of solute
(moles of solute) x (the I value)= moles of particles in solution
what is the SCE method
sodium chloride equivalent method
used to find the equivalent concentration of sodium that yields the same tonicity as concentration of a given substance
what is the SCE value of a substance
value factor for a given substance that converts its tonicity to the equiv. tonicity of sodium
how to calculate SCE value if not given experimental one
divide the molar concentration of a substance (in mM) by 277mM
examples of how to find SCE value if not given experiemental
find sce value of 9 g of dextrose (MW: 180.16g/mol)
find sce value of 9 g of dextrose (MW: 180.16g/mol)
9 g/X mol=180.16 g/mol
X=0.05 mol
I value = 1: so 0.05molx1=0.05 mol
0.05mol= 50 mM
50mM/277mM=0.181 (SCE value)
9g x 0.181=1.629 g of NaCl
examples of how to find SCE value if not given experiemental
find sce value of 9 g of potassium cl (MW: 74.55g/mol)
9 g/Xmol= 74.55 g/mol
X= 0.121 mol
0.121 (1.8 {I Value})=0.217 mol
0.217 mol= 217 mM
217mM/277mM= 0.783 {SCE value}
9g x 0.783=7.047 g
what is the experimental SCE for KCl and what does that tell us
~0.76
represents an approx 3% diff in calculates SCE value
we should use reliable experimental data whenever possible
rely on calculated sce value when he I value is known to be accurate
example of how to determine how much substance needed to make a solution isotonic
- how much KCl would be required to compound 30 mL of an isotonic solution containing 0.35% w/v NaCl?
how much KCl would be required to compound 30 mL of an isotonic solution containing 0.35% w/v NaCl?
- find out how much NaCl would be in 30 mL of a 0.35% w/v solution
0.35g/ 100 mL= Xg/30mL
X= 0.105 g
- now calculate how much NaCl is in 30 mL of NS. (because NS is isotonic, conc of NaCl in that solution will be an isotonic concentration we can compare our value to)
0.9 g/100 mL=Xg/30 mL
X=0.27 g
- as we can see, the amount of sodium we need in our solution is less than the amount calculated to make 30 mL of an isotonic solution. now calculate how much more sodium we would need to get the isotonic sodium value for our volume
0. 270g-0.105 g= 0.165 g or 165 mg
we would need 0.165 g more sodium to make the solution isotonic. however, the solution only intended to have 0.35% w/v in sodium. that means that we have to find the equivalent mass of KCl to yield that tonicity
must use the SCE value of KCL:
165mg / 0.76 {KCl SCE value}=217 mg of KCl
how much Nacl would be required to compound 15 mL of an isotonic solution of 1% atropine sulfate monohydrate (SCE value =0.12)
how much Nacl would be required to compound 15 mL of an isotonic solution of 1% atropine sulfate monohydrate (SCE value =0.12)
- 1g/100mL=Xg/15mL
X=0.15g Atropine - 0.15g x0.12 {SCE value}=0.018g
- 0.9g/100mL=Xg/15mL
x=0.135g - 0.135g-0.018g=0.117 g or 117 mg
what is the freezing point of a solution containing 20 mg/mL caffeine and 3% NaCL w/v.
NaCL: MW= 58.44 g/mol
I value: 1.8
Caffeine: 194.19 g/mol
2 ways to get this answer
- find out conc of each in a liter
- find out molar concentration of each
- add them together
- multiple by freezing point depression value
caffeine: 20 mg/ 1 mL= Xmg/1000mL
X=20,000 mg or 20 g
20g/Xmol=194.19g/mol
X= 0.103 mol
NacL: 3g/100mL=Xg/1000mL
X= 30 g
30g/Xmol=58.44 g/mol
X=0.513 mol
0.513 mol x 1.8{I value}=0.924 mol
- 103 mol+0.924 mol=1.03 mol
- 03 mol x 1.86 C degrees =1.92 C degrees
THIS IS THE FREEZING POINT DEPRESSION
THE FREEZING POINT IS -1.92 degrees C
second way:
consider %NACL (or equiv.)
NaCl: 3%
caffeine: 20 mg/ml= Xg/100 mL
X= 2000 mg or 2 g of caffeine. sooo 2% w/v
2% x 0.17 {SCE value}=0.34%
3%+0.34%=3.34%
Ratio
0.9%/ 0.52 C degrees (freezing point depression of NS)=3.34%/ X C degrees
X=1.93 C degrees
freezing point =-1.93 degrees C
basic steps of SCE method
***pH not an issue
- determine and weigh required amount of drug
- calculate amount of NaCL in an isotonic volume equiv to compounded volume
- multiply calculated drug mass by SCE value
- subtract step4 from 3. weigh this amount of Nacl
- place nail and drug in beaker. dissolve in minimal amount of H2O, quantitatively transfer to a GC, qs to final volume with h20. mix by pouring
- cold filter sterilize, transfer to dispensing container
OU vs OS vs OD
rx abréviation meaning
OU: both eyed
OD: right eye
OS: left eye
benzalkalonium chloride
preservative for eyedrops
what do you do if you have to weigh a volume that is below minimal weighable quantity
make a dilution. use judgement as to what volume dilution is reasonable.
what should you do if you have to measure a volume that we can technically measure given our volume instruments but is small
ex: measure 1.5 mL
divide the volumeinto 2 and measure that volume twice.
1.5/2= 0.75 mL
measure this volume twice
what are the 3 methods of ophthalmic compunding considered in this course
- SCE method
- USP method
- Sorensen Phosphate Buffer Method
USP method
what is”theorem A”
when does it not hold true
if you add an isotonic solution (of any volume ) to a second isotonic solution (of any volume), the resulting solution will be isotonic
does not hold true if these occur... precipitation drug degredation chemical reaction and solutions must be miscible
USP method
V-value
the amount of H2O required for the dissolution of 300 mg of drug which results in an isotonic solution
USP method
what is the assumption of the USP method
1, contribution of the solute ott he overall solution volume is negligible
concentration: 300 mg/V-value.
how to us USP method in Rx
ex:
Rx
atropine sulfate 1.125%
Nacl qs
H2O: qs ad 15 mL
(Atropine v value: 4.3 mL)
make a 300 mg/4.3 mL atropine solution
- atropine
1.125g/100 mL=Xg/15 mL
X=0.169 g or 169 mg
300mg/4.3 mL= 169mg/XmL
X=2.42 mL of
you would put 2.42 mL of atropine solution in a GC, then QS to 15mL with NS.
Is there a difference between resulting ingredient compositions when using the SCE or USP method?
NO.
does the USP method take pH into account?
no
Sorensen Phosphate Buffer Method
basic steps
- pH is an issue
- Pharmacist has direct control over product pH
- prepare an excess buffered stock solution of appropriate proportion to yield desired pHh in final product.
- calculate and weigh required amount of drug
- multiple mass by SCE value
- determine NACL required volume of product with out drug content
- subtract nacl mass equiv. from total nail equiv. to yield NacL required.
- place drug and nail in beaker, dissolve. qs to final volume with buffered stock solution. mix by pouring, etc.
- sterilize, transfer to dispensing container, label, dispense
how to determine volumes of sodium diphosphate and sodium phosphate to make buffer solution
look at sorensen phosphate buffer chart.
look at required percentages of each solution for required pH.
Use to make solution for required compounding volume
in the sorensen method, how to determine amount of Nacl in an isotonic solution for required compounding volume if it only contained Nacl.
how does this differ from the SCE mthod
must use the NacL required for isotonicity from the sorensen method chart for that specific pH value.
different cause in the SCE method, you find the requiredNaCL by using the concentration of NS
how to convert between C and F
1.8C=F-32
freezing point of D10W
- 10g/100 mL= Xg/1000mL
X= 100g
2.100g/X mol=180g/mol
X= 0.556 mol
- 0.556 mol(1.86 C degrees)= 1.03 C degrees (freezing point depression)
Freezing point: -1.03 degrees C
