the medicine Flashcards
What is the effect of temperature on stability?
temperature affect the rate of drug degradation by enhancing all chemical processes involved
Roughly a 10°C increase in temperature will produce a 2 to 3 fold increase in the rate of reaction
Can cause the Arrhenius equation to predict the effect of temperature on reaction rate
what is -Ea/R
gradient
what is InA
y intercept
strategies to increase stability (instability due to hydrolysis)
remove water - add a desiccant or change solvent
Lower water activity - add cosolvent
Reduce hygroscopic nature - change salt
Formulate as a solid - powder for reconstitution
strategies to increase stability (instability due to oxidation)
remove oxygen-store, and the nitrogen, carbon dioxide or helium
Buffer at PH3 to 4-oxidation is enhanced by anions
add an antioxidant-sodium metabisulphite
chelate metal ions-edetate disodium
strategies to increase stability (instability due to photo lysis)
Protect from light (packaging)
Strategies to increase stability (PH)
Store at a pH minimum
strategies to increase stability (temperature effects)
Store in cold places less than 15°C
Refrigerate (4°C)
Pharmacokinetic considerations in absorption rate
aqueous solutions are the best dosage form for rapid and predictable drug absorption from the gastrointestinal tract
But we need to consider solubility, stability, taste, and economic issues
Most patients still prefer solid dosage forms
give some examples of excipients in the formulation of solutions
Solvents
chelating agents
Colouring
Preservatives
Sweetening agents
Antioxidants
Clarification agents
Flavourings
Solubilising agents
Viscosity modifiers
Give examples of solvent from aqueous systems
water
Ethanol
Iso propanol
Polyethylene glycol
Propylene glycol
Glycerin
Give some examples of solvent for oily systems
isopropyl myristate
Mineral oil
Peanut oil
Corn oil
Cottonseed oil
Sesame oil
what are examples of antioxidants for aqueous systems
sodium metabisulphite
Ascorbic acid
Citric acid
Malic acid
Give examples of antioxidants for oily systems
butylated hydroxyanisole
butylated hydroxytoluene
give examples of chalating agents
edetate disodium
give examples of clarifying agents
bentonite
give examples of flavouring agents
bitter
sour
salty
sweet
anaesthetic: methanol/ peppermint oil
indigestion remedies associated with mint
may use flavour enhancers eg. citric acid for citrus fruits
What do you need to ensure when choosing a preservative?
that there is no adsorption of a preservative onto the container
efficiency is not impaired by the pH or other exceptions
What are solubilising agents?
use surface acting agents to form micelles
Surfactant concentration is key (toxicity or insufficient solubilisation)
What is the most widely used as a sweetener agent?
Low, molecular weight carbohydrates (sucrose)
What is the benefit of using viscosity modifiers?
they are especially useful for topical solution is placed on the skin, or in the eyes
Low concentrations of gelling agents can be used to increase the viscosity of the solution
what will parental solutions require?
Some specific excipients
buffers
Tonicity modifiers
What to do eyedrops require?
To be sterile
what is it important for nasal and ear products to be?
their viscosity is important
what is important for mouthwashes and gargles
taste
What is the importance of carbohydrates?
they are distributed widely in nature
They are key intermediate of metabolism (sugar)
They provide a range of cellular markers
Some are used as excipients
How many oxygen and carbons do carbohydrates roughly have
roughly equal number of each
3 carbons
trioses
4 carbons
tetroses
5 carbons
pentoses
6 carbons
hexoses
7 carbons
heptoses
what is the fischer projection
D or L configuration at the bottom
most oxidised group- CHO top, X-OH bottom
vertical substituents are away, horizontal, substituents are towards
what’s aldose
contains an aldehyde and is a monosaccharide
what is ketose
contains a ketone and is a monosaccharide
what are the consequences of monosaccharide asymmetry
A carbon have in four different groups attached is asymmetric (Chiral)
Transporting any two of the groups on a chiral carbon results in a different compound with different physical properties
The number of allison this is 2^n where n is the number of asymmetric carbons
most sugars are therefore optically active
(can rotate a beam of plane polarised light)
what are epimers
sugars that differ at a single asymmetric centre
what are enantiomers
sugars that differ at all of that asymmetric centres and are mirror images
what are diastereoisomers
sugars that differ at one or more chiral centres. And that are not enantiomers
what are aldotetroses
they have two chiral centres
what is cyclisation
a chemical reaction where a molecule undergoes a ring closing reaction
what does pentose cyclisation form
pyranose rings
what does hexoses cyclisation form
furanose
what are anomers
intermolecular nucleophillic addition creates cyclic hemiacetals in sugars
formation of the cyclic hemiacetal creates an additional chiral centre giving two diastereoisomeric forms alpha and beta
these diastereoisomers are called anomers
alpha monosaccharides
Hydroxyl group sits below the plane of the Ring (carbon one)
Beta monosaccharides
Hydroxyl group sits above the plane of the Ring (carbon one)
what is mutarotation
where the cyclic structure of a sugar molecule undergoes a rapid equilibrium between the alpha and beta anomers in aqueous solution
occurs due to the hydroxyl groups next to it rotate freely. therefore equilibrium can be shifted by external factors eg. them, pH, and []
what is mannitol
it is used to prevent or treat excess body water in certain kidney conditions
Reduces swelling of the brain
Reduces pressure in the eye
It is an osmotic diuretic, it works by increasing the amount of fluid excreted by the kidneys, and helps the body to decrease pressure in the brain and eyes.
what is sorbitol
it is a laxative
It is used to treat constipation
what is a glycosidic bond
carbohydrates are joined to alcohols and amines at the anomeric centre by glycosidic bonds
what is a disaccharide
combines a hydroxyl of one monosaccharide and an acetyl linkage with another monosaccharide C1 and C4
what is lactose
a disaccharide that occurs naturally in milk
it is a reducing sugar
exhibits mutarotation
cleaved in digestion to glucose and galactose
why is lactose a common excipient
used to help form tablets because it has excellent compress ability properties
It is used to formate diluent powder for dry powder inhalations
what is mannose
a common excipient
what is maltose
a common excipient
what is sucrose
‘table sugar’
pure sucrose, a disaccharide that hydrolyses to glucose and fructose
does not undergo mutarotation
what is glycogen
a polysaccharide that serves the same energy stronger function in animals that starch serves in plants
highly branched and larger than amylopectin
up to 100,000 glucose units
what are amino sugars
they are found in antibiotics
occurs in cartilage
what are grooves in DNA
the strands of the DNA double helix create two continuous grooves major and minor
major groove is wider and deeper
what is aciclovir
a purine based antiviral drug acting against herpes
guanine base
the acyclic hydroxy ether substitutet mimics the sugar of the natural nucleoside
achiral - cheaper to make
acts as a chain terminator in viral DNA replication
what is a chain terminator
nucleoside analogues which interfere with or halt DNA replication
eg Aciclovir
what is interstrand
crosslinking can occur between two complementary strands of DNA
what is intrastrand
crosslinking happening between a single strand of DNA (within a strand) as generated by cisplatin
what is temozolomide
a pro drug against brain tumours discovered at aston
crossed the Blood brain barrier
undergoes chemical transformation to yield
the reactive methylating agent
what is doxorubicin
an example of a DNA intercalator
what is a DNA intercalator
they are molecules capable of fitting between nucleic acid base pairs
what is the therapeutic difference between citerazine hydrochloride and di hydrochloride
There’s no therapeutic different apart from they are both stereoisomers
