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Pharmaceutical calculations GPAt, Study notes of Pharmacy

Pharmaceutical calculations for Exam like GPAT FPGEE

Typology: Study notes

2018/2019

Uploaded on 09/10/2019

gurpreetpharma85
gurpreetpharma85 ๐Ÿ‡ฎ๐Ÿ‡ณ

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PHAR1822(Notes(
Pharmaceutical(calculations(
๐‘‘=
๐‘š
๐‘ฃ!
๐‘‘๐‘’๐‘›๐‘ ๐‘–๐‘ก๐‘ฆ!(๐‘”/๐‘š๐ฟ)=!
๐‘š๐‘Ž๐‘ ๐‘ !(๐‘”)
๐‘ฃ๐‘œ๐‘™๐‘ข๐‘š๐‘’!(๐‘š๐ฟ)!
๐‘=
๐‘›
๐‘ฃ!
๐‘๐‘œ๐‘›๐‘๐‘’๐‘›๐‘ก๐‘Ÿ๐‘Ž๐‘ก๐‘–๐‘œ๐‘›!(๐‘š๐‘œ๐‘™ ๐ฟ)!=
๐‘š๐‘œ๐‘™๐‘’๐‘ !(๐‘š๐‘œ๐‘™)
๐‘ฃ๐‘œ๐‘™๐‘ข๐‘š๐‘’!(๐ฟ)!
๐‘›=
๐‘š
๐‘€๐‘€!
๐‘›๐‘œ.๐‘š๐‘œ๐‘™๐‘’๐‘  =!
๐‘š๐‘Ž๐‘ ๐‘ !(๐‘”)
๐‘š๐‘œ๐‘™๐‘’๐‘๐‘ข๐‘™๐‘Ž๐‘Ÿ!๐‘š๐‘Ž๐‘ ๐‘ !(๐‘”๐‘š๐‘œ๐‘™)!
๐‘!๐‘ฃ!=๐‘!๐‘ฃ!!
๐‘ข๐‘ ๐‘’!๐‘“๐‘œ๐‘Ÿ!๐‘‘๐‘–๐‘™๐‘ข๐‘ก๐‘–๐‘œ๐‘›๐‘ !
!
" dL!=!decilitre!=!100mL!
" If!a!mixture!is!made!up!of!water!and!drug,!add!x!grams!of!drug,!and!then!(100!โ€“!x)!mL!of!water!to!
make!the!mixture!a!total!amount!of!100mL!(or!100g)!
o I.e.!add!water!to!make!the!volume!up!to!100mL!!
" Dilution!โ‰ˆ!paediatric!sample!โ€“!use!C1V1=C2V2!
" If!working!with!a!liquid!drug!or!solvent!other!than!water!(e.g.!ethanol)!โ€“!density!formula!!
!
Liquids(and(Solutions(
Solution(
Mixture!of!two!or!more!components!that!form!a!single!phase!which!is!homogeneous!
down!to!the!molecular!level!
Phase(
Part!of!a!system!separated!by!one!or!more!boundaries/interfaces,!which!can!be!
separated!physically!(e.g.!filtration,!centrifuge)!
Dissolution(
Transfer!of!molecules!or!ions!from!the!solid!state!into!solution!
Miscibility(
Combination!of!two!solvents!that!mix!completely!to!form!a!homogenous!solution!
!
Solubility!
" Limit!to!which!a!solute!can!be!dissolved!in!a!solvent!under!a!particular!set!of!conditions!
" Determined!at!20ยฐC!
" Based!on!amount!of!solvent!in!mL!or!grams!(โ€œpartsโ€),!required!to!dissolve!1g!of!drug/excipient!
o Soluble!โ€“!10"30!parts!solvent!
o Insoluble!โ€“!>10000!parts!solvent(!
" Water!solubility!โ€“!depends!on!polarity!and!functional!groups!โ€“!H"bonds!and!ion"dipole!bonds!!
o "NH,!"OH!or!C=O!functional!groups!will!H"bond!with!water!
o Ion"dipole!bonds!are!even!stronger!than!hydrogen!bonds!
!
Salt!form!of!drugs!
" Salt!form!of!drugs!are!more!water!soluble!than!neutral!form!
" They!form!more,!and!stronger,!hydrogen!bonds!with!water!
" However:!
o Samples!can!be!hygroscopic!(draw!in!moisture!from!air)!
o Can!change!pH!of!solution!(important!for!injection!and!oral!solutions)!
o Reactions!with!packaging!(glass!and!basic!solutions)!
o Different!salts!of!a!drug!can!work!differently!
o Salts!interact!with!each!other!and!precipitate!out!of!solution!!
" Most!common!salt!forms!of!drugs:!
o Acidic!drugs!โ€“!Na+,!K+,!Ca2+,!Zn2+!
o Basic!drugs!โ€“!Cl",!SO4
2",!PO4
3"!
!
Salting!out!
" Precipitation!of!peptides!and!proteins!from!solution!at!high!salt!concentrations!
" At!high![salt],!water!molecules!bind!to!the!salt!instead!of!the!protein!(not!enough!free!water!
available)!โ€“!causes!precipitation!of!protein!molecules!(less!soluble!solute)!
" Some!drugs!based!on!proteins!and!peptides!โ€“!must!ensure!drugs!do!not!precipitate!
(
Drug/mixture(
w/w!
grams/100g!
w/v!
grams/100mL!
v/v!
mL/100mL!
v/w!
mL/100g!
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PHAR1822 Notes Pharmaceutical calculations ๐‘‘ =

๐‘ฃ ๐‘‘๐‘’๐‘›๐‘ ๐‘–๐‘ก๐‘ฆ^ (๐‘”/๐‘š๐ฟ)^ =^

๐‘ฃ ๐‘๐‘œ๐‘›๐‘๐‘’๐‘›๐‘ก๐‘Ÿ๐‘Ž๐‘ก๐‘–๐‘œ๐‘›^ (๐‘š๐‘œ๐‘™^ ๐ฟ)^ =^

๐‘€๐‘€ ๐‘›๐‘œ.^ ๐‘š๐‘œ๐‘™๐‘’๐‘ ^ =^

-ยญโ€ dL = decilitre = 100mL -ยญโ€ If a mixture is made up of water and drug, add x grams of drug, and then (100 โ€“ x) mL of water to make the mixture a total amount of 100mL (or 100g) o I.e. add water to make the volume up to 100mL -ยญโ€ Dilution โ‰ˆ paediatric sample โ€“ use C 1 V 1 =C 2 V 2 -ยญโ€ If working with a liquid drug or solvent other than water (e.g. ethanol) โ€“ density formula Liquids and Solutions Solution Mixture of two or more components that form a single phase which is homogeneous down to the molecular level Phase Part of a system separated by one or more boundaries/interfaces, which can be separated physically (e.g. filtration, centrifuge) Dissolution Transfer of molecules or ions from the solid state into solution Miscibility Combination of two solvents that mix completely to form a homogenous solution Solubility -ยญโ€ Limit to which a solute can be dissolved in a solvent under a particular set of conditions -ยญโ€ Determined at 20 ยฐC -ยญโ€ Based on amount of solvent in mL or grams (โ€œpartsโ€), required to dissolve 1g of drug/excipient o Soluble โ€“ 10 -ยญโ€30 parts solvent o Insoluble โ€“ >10000 parts solvent -ยญโ€ Water solubility โ€“ depends on polarity and functional groups โ€“ H-ยญโ€bonds and ion-ยญโ€dipole bonds o -ยญโ€NH, -ยญโ€OH or C=O functional groups will H-ยญโ€bond with water o Ion-ยญโ€dipole bonds are even stronger than hydrogen bonds Salt form of drugs -ยญโ€ Salt form of drugs are more water soluble than neutral form -ยญโ€ They form more, and stronger, hydrogen bonds with water -ยญโ€ However: o Samples can be hygroscopic (draw in moisture from air) o Can change pH of solution (important for injection and oral solutions) o Reactions with packaging (glass and basic solutions) o Different salts of a drug can work differently o Salts interact with each other and precipitate out of solution -ยญโ€ Most common salt forms of drugs: o Acidic drugs โ€“ Na+, K+, Ca2+, Zn2+ o Basic drugs โ€“ Cl-ยญโ€, SO 42 -ยญโ€, PO 43 -ยญโ€ Salting out -ยญโ€ Precipitation of peptides and proteins from solution at high salt concentrations -ยญโ€ At high [salt], water molecules bind to the salt instead of the protein (not enough free water available) โ€“ causes precipitation of protein molecules (less soluble solute) -ยญโ€ Some drugs based on proteins and peptides โ€“ must ensure drugs do not precipitate Drug/mixture w/w grams/100g w/v grams/100mL v/v mL/100mL v/w mL/100g

-ยญโ€ Van der Waals radius โ€“ imaginary radius of an atom or molecule o Physical space the drug/particle takes up -ยญโ€ Hydrodynamic radius โ€“ imaginary radius of drug/particle and any bound subparticles (e.g. water) that travel through the solution with the drug particle -ยญโ€ Brownian motion โ€“ random movement of particles suspended in a liquid or gas o Caused by collisions with molecules of the surrounding medium o Rate of drug/particle movement through solution is directly related to size Stokes โ€“ Einstein equation -ยญโ€ Rate at which drug diffuses through solution is largely dependent on hydrodynamic radius and solvent viscosity -ยญโ€ ๐ท = !" !!"# o D = diffusion coefficient (m^2 s-ยญโ€^1 ) o K = Boltzmann constant (1.3810-ยญโ€^23 JK-ยญโ€^1 ) o T = temperature (K) o ฮท = solvent viscosity (water: 1.23210-ยญโ€^3 Pa S) o r = hydrodynamic radius (metres) Vapour pressure -ยญโ€ Pressure of vapour above liquid when liquid and vapour are at equilibrium -ยญโ€ Amount of vapour about liquid depends on intermolecular forces o More bonding between molecules โ€“ less vapour formed โ€“ lower vapour pressure -ยญโ€ Lower vapour pressure โ€“ boils at higher temperature -ยญโ€ Higher vapour pressure โ€“ boils at lower temperature -ยญโ€ 50/50 mixture of ethanol and water o Does NOT mean mixture of vapour is also 50/ o More ethanol molecules in air than water since ethanol has a higher vapour pressure -ยญโ€ ๐‘ƒ!"!#$ = ๐‘‹!๐‘ƒ! + ๐‘‹!๐‘ƒ! o Ptotal = total pressure from all molecules in the gas/vapour phase o XA = mole fraction of gas A ยง๏‚ง Total of mole fractions (XA + XB) must equal 1 o PA = vapour pressure of gas A o Raoultโ€™s Law 2 polar molecules 1 polar 1 non-ยญโ€polar 2 non-ยญโ€polar H-ยญโ€bonding โ€“ keeps in liquid phase Repulsion โ€“ more molecules in gas/vapour phase Ideal conditions Hydrophobic forces very weak; no repulsion Lower vapour pressure for both Higher BP Higher VP Lower BP No effect on partial pressures of the gases/vapours Freezing point depression -ยญโ€ Dissolution of polar solute into a solvent results in drop in the freezing point of the solvent o Salt + water โ€“ lowers freezing point, so water doesnโ€™t freeze as easily o Blood contains many polar molecules (proteins, salts) โ€“ lowers freezing point of blood -ยญโ€ Size of FPD depends on solvent and amount of solute (no. molecules, not no. moles) -ยญโ€ Any solution injected into vein, or eye drops โ€“ must have FDP of 0.52ยฐC Change Rate of drug diffusion Increase temperature Faster Change form water to oil Slower Change from neutral drug to salt form Slower Make a nanoparticle formulation of the drug Slower