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Solutions Flashcards

0
Q

What is a binary solution?

A

A mixture of only 2 components:

Solute + solvent

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1
Q

What is a solution?

A
  • Chemical and physical homogenous minute of 2 or more components
  • A 1 phase system
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2
Q

Why is a solution also called a molecular dispersion?

A

The solute is dispersed as molecules or ions in the solvent

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3
Q

What are examples of where the solute is present in a greater amount than the solvent?

A

In syrups

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4
Q

What are the steps in forming a solution?

A

1) abstraction of solute molecule. This depends on the strength of the crystal lattice. This consumes energy
2) creation of cavity in solvent molecule. This depends on the cohesive forces of the solvent. This also consumes energy
3) insertion of solute molecule into solvent. This liberates energy. The larger the excess of this liberated energy, the more soluble the solvent

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5
Q

What are the main solutions of focus in these lecture series

A

Gas in liquid e.g. Carbonated water
Liquid in liquid e.g. Alcohol in water
Solid in liquid e.g. Aqueous sodium chloride solution

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6
Q

What are the advantages of solution dosage forms?

A

Easy to swallow: has paediatric and geriatric use
Rapid onset of action: drug is immediately available for absorption
Uniform drug distribution: solution is a homogenous mixture
Reduced local irritation: immediate dilution
Various routes of administration possible: oral, inhalation, IV, IM, etc

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7
Q

What are disadvantages of solution dosage forms?

A

Bulky, inconvenient to transport and store
Stability issues: esp. For drugs prone to hydrolysis
General reduced shelf life compared to solid form of same drug
Prone to microbial growth: preservative required
Dosing issues: patient may find it hard to measure 3.33ml
More pronounced taste if drug than if it were in solid form: requires flavourants

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8
Q

What are some pharmaceutical solvents?

A 
Water 
Fatty oils 
Alcohols 
Dimethylsulphoxide
Ethyl ether
Xylene
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9
Q

What is the most widely used aqueous vehicle and why?

A

Water

  • high physiological compatibility
  • lack of toxicity
  • high dielectric constant (allows dissolution of wide range of drugs)
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10
Q

What are the disadvantages of using water as a solvent?

A
  • lack of selectivity during drug dissolution

This complicates the extraction of unwanted substances like inorganic salts and organic impurities

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11
Q

What are the types of pharmaceutical water?

A 
Purified water (used for boiling/cooling, distillation, deionisation, reverse osmosis)
Water for injections (used for Pareneteral formulations: e.g. Formulation of drugs sensitive to CO2 like phenobarbitone sodium, aminophylline, or drugs sensitive to oxidation like apomorphine and ergotamine maleate)
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12
Q

What are the main approaches to improve aqueous solubility?

A 
Co solvency
PH control
Solubilisation
Complexation
Chemical modification
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13
Q

How does co solvency improve aqueous solubility?

A

We can change the dielectric constant of the solvent to make it more compatible with the drug however the choice of cosolvent is limited in pharmaceutical use. E.g. For oral administration you should avoid a toxic cosolvent

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14
Q

How does pH control improve aqueous solubility?

A

A weakly acidic or weakly basic drug has an intrinsic pKa value. This makes them prone to change their proportion of ionisation depending on the pH of the environment.
We can change the pH to favour a higher proportion of ionisation making it more dissolvable in aqueous solvents

However we should be careful that the chosen pH of the formulation does not conflict with other product requirements like issues with stability

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15
Q

How does solubilisation improve aqueous solubility?

A

We can add surfactants into the formulation (generally with HLB>15) these include simple micelles, liposomes, liquid crystals, or cyclodextrins.
These molecules have a polar and non polar portion and will bind to the drug and the solvent to help solubilise it

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16
Q

How does complexation improve aqueous solubility?

A

We can add a hydrophilic complex to the poorly soluble drug to make it more soluble however this needs to be reversible in order to allow the drug to cross through the biological membrane after it has dissolved and reached its target site

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17
Q

How does chemical modification improve solubility?

A

We can use the salt form of water insoluble drugs as they are more soluble. E.g. Sodium phosphate salts of hydrocortisone, prednisolone and betamethasone are often used

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18
Q

Why are non aqueous solutions used?

A

To overcome solubility and stability issues associated with aqueous systems
Have the ability of exhibit sustained release properties (e.g. Oily injections, oily eye drops)

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19
Q

What factors need to be considered when working with non aqueous solutions.

A

Toxicity, irritancy, flammability, cost, stability, compatibility with other ingredients

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20
Q

What does the choice of a non aqueous solvent depend on?

A

Route of administration

Topical > oral > Pareneteral

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21
Q

What fatty oils are used as non aqueous solvents?

A

Fatty oils = fatty acid esters of glycerol
E.g.

Almond oil, arachis oil, olive oil, sesame oil, maize oil, soya oil, castor oil,

Many are suitable for Pareneteral use

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22
Q

Which oil is used for injections?

A

Ethyl oleate: it is less viscous, easily injectable

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23
Q

What oil is used for oral administration?

A

Fractionated coconut oil

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24
What oil is used for external preparations?
Unpleasant oils, unless they are formulated as an emulsion then they can be considered for oral use as well (provided they are non toxic)
25
What are the advantages of using lipid solutions for oral use?
Lipids can act as a solvent for lipophilic drugs There is no dissolution required as the drug enters the GIT in solution form (normally this dissolution would have been a rate limiting step) Lipid solutions are useful for poorly water soluble drugs with low bioavailability and high lipid solubility
26
How is the bioavailability improved for lipid solutions?
In a lipidic solution, when the fats are dissolved the drug does too. This then goes into the lymphatic network. This is a good network for the transport  of poorly water soluble drugs and those which usually go through first pass metabolism.  This lymp carries a lot of your white blood cells and other fluids.  Capillaries are a bit leaky, so some molecules can leak out.  This system is lipid based and carries stuff back. We can Hijack the lymphatic transport for our poorly soluble drugs. The lymphatic system does not go through the liver hence avoiding first pass metabolism. Lymph goes straight into venous system near the heart (sub clavian and superior vena cava) and then body  Thus bioavailability is increased.
27
How are lipids absorbed?
Lipase enzyme binds to the lipid droplet to form a colipase/lipase complex. Liquid crystalline layers can be seen at the droplet surface. Endogenous bile salts and phospholipids then bind, along with lipid digestion product. These help the lipid to absorb across the cell membrane
28
What are the disadvantages of using the lymphatic system?
Tmax may be increased as the lymphatic system relies on muscular contractions and is very slow
29
What are the common alcohols used in non aqueous solvents?
Ethyl alcohol (ethanol) Isopropyl alcohol Polyhydric alcohols
30
Why is ethanol used?
This is the most widely used nan aqueous alcoholic solvent - rapid evaporation after application - has antimicrobial activity at concentrations >15% but is toxic at this concentration also
31
Why is isopropyl alcohol used?
This is an aliphatic alcohol with similar properties to ethanol - IPA widely replaces ethanol in external formulations - has the abuse potential as an extraction solvent for some controlled drugs from conventional dosage forms - not ingestible
32
Why are Polyhydric alcohols used?
Used in conjunction with water as a cosolvent | E.g. Polyethylene glycol, macrogols, glycerol (which can act as a cosolvent and sweetener for diabetic formulations)
33
What other non aqueous solvents are used.?
Dimethyl sulphoxide -highly polar used as penetration enhancer in dermatological preparations Ethyl ether - used as cosolvent in combination with alcohol in topical collodions Xylene - used in ear drops to dissolve ear wax
34
What other formulation additives may be present in a liquid dosage formulation?
``` Buffers Isotonicity modifiers Viscosity modifiers Preservatives Antioxidants Sweeteners Flavourants and colouring agents ```
35
Why are buffers added?
To enable the solution to resist changes in pH
36
What does the choice of buffer depend on?
PH Buffer capacity required Routes of administration
37
What are commonly used buffer systems based on?
``` Carbonates Citrates Gluconates Lactates Phosphates Tarates Borates (topical only) ```
38
What criteria must buffers meet?
Be buffered at pH of biological fluids to avoid irritation. Especially for injections, oral and nasal formulations however compromises are possible
39
Why are isotonicity modifiers added?
Solutions for injection, application to mucosa membranes or large volume opthalmic solutions need to be formulated ISO-osmotic ally to avoid pain and irritation to the patient. E.g. Dextrose, sodium chloride (0.9%)
40
Why is tonicity adjusted after addition of other ingredients?
Because other ingredients will also affect the tonicity of the solution so it needs to be altered last.
41
Why are viscosity enhancers used?
Increasing viscosity of the solution prolongs the contact time of aqueous solutions with biological membranes like skin, or eye We often use cellulose derivatives like HPMC, HEC, carbopol, chitosan, Viscosity may also exhibit mucosa adhesive abilities
42
What is sol to gel phase transition?
We can use polymers which undergo solid to gel phase transition when exposed to a change in a physicochemical parameter e.g. Ionic strength, temperature, pH, solvent exchange. This enables easy instillation of the solution in liquid form, increased residence time of the formulation on the ocular surface due to the gelling which is an increase in viscosity
43
Why are preservatives added.
To prevent microbial growth | To prolong the shelf life of the formulation
44
What is an ideal preservative.
One which Does not adsorb onto the container Does not interact with other ingredients Is not affected by the pH of the solution
45
How are parabens affected by pH fluctuations?
They have a pKa of ....
46
Does a syrup need a preservative?
No because the higher solute proportion causes an osmotic effect in microbes which causes all the water to be sucked out of them thus inhibiting microbial growth
47
Why do reducing agents or antioxidants need to be added to solutions?
To prevent redox reactions and increase stability and shelf life. We often use sodium metabisulfite, butylated hydroxyanisole, toluene, vitamin c and e
48
Why do sweetening agents need to be added into solutions?
To mask the bitter taste of the active ingredient which is often the case
49
What are common examples of sweetening agents added into solutions?
Sucrose: colourless, very soluble in water, stable over broad pH range,increases solution viscosity, masks the taste of salty and bitter drugs, has a soothing effect, Mannitol, sorbitol, glycerol: for diabetic preparations Artifical sweeteners (saccharin, aspartam): very potent. Only 0.2% is needed but leave a bitter metallic after taste
50
Why are flavouring agents added?
To mask the taste of particularly unpleasant tasting drugs | Useful in paediatric formulations
51
Why are colouring agents added?
For attractiveness and product identification
52
What are the different types of pharmaceutical solutions?
Oral solutions Topical solutions Ophthalmic solutions Parenteral solutions ``` There are also ear preparations, Nasal products, Irrigations, Mouthwashes Enemas ```
53
What are the characteristics of an oral solution?
Taken internally Additives used for flavour and viscosity Water as solvent
54
What are the different types of oral solutions?
Dry mixtures for reconstitution Elixir Linctus Syrups
55
Why is a dry mixture for reconsittution?
Antibiotics are unstable in the presence of water so they are kept as powder and made up when needed. When water is added, they must be stored into the fridge. Shelf life limited to 7-14 days
56
What is an elixir?
Solution containing a potent drug Often contains high proportion of alcohol and syrup E.g. Paediatric paracetamol elixir Some elixirs require the addition of a preservative. This depends on the amount of ethanol in it. A high proportion of ethanol would therefore not require a preservative
57
What is a linctus?
A viscous preparation usually for cough relief Contains a high concentration of sucrose E.g. Codeine linctus diabetic
58
What is a syrup?
Concentrated solution of sucrose or other sugars May or may not contain an active ingredient (depends on its use- some are non medicated) High concentrations of sucrose works as a viscosity modifier and taste masking, Does not require preservatives due to osmotic effect as a result of 85% sucrose. In a closed container surface dilution can occur as a result of internal solvent evaporation and condensation hence additional preservatives may still be used
59
What are the characteristics of topical solutions?
Used for application to skin or mucous membranes, Solvents can be aqueous or alcoholic ``` E.g. Lotions Liniments Paints Colloidions ```
60
What is a lotion?
This is applied to the skin without friction May contain humectants (which retain moisture in skin) Or alcohol (which leaves a cooling effect when it evaporates
61
What is a liniment?
This is intended for massage into the skin Contains counter irritants or anti-inflam drugs Useful in strains and muscle spasms
62
What is a paint?
Liquids for applications of small quantity toes to a specific area of the skin using a small brush E.g. Salicylic acid paint for wart treatment
63
What is a colloidion?
Similar to a paint. Contains volatile solvents which evaporate and leave a tough and flexible film to seal small cuts or hold a drug in close contact with the skin
64
What are the characteristics of opthalmic solution?
For use in the eye. Additives are generally used for viscosity. Solution is free from particles and is isotonic and sterile
65
What are the criteria for opthalmic solutions?
Typical corneal contact time 1-2 mins Bioavailability <10% PH between 7.0-7.7 (but for stability purposes, a pH of 5-9 is still okay without causing inflammation) Isotonic (310-350mOsm/kg) hypotonic solutions better tolerated than hypertonic Viscosity modifiers needed to increase ore ocular retention and better drug bioavailability
66
What are the characteristics of parenteral solutions?
``` Used for injection IV, IM, SC Have few additives There are rigid standards for sterility Free of particulates, pyrogens Isotonic Have immediate effect ```
67
What are immediate products?
Designed to be used during the manufacture of other dosage forms E.g. Aromatic waters, syrup, extracts, infusions, tinctures, colouring agents
68
What are aromatic waters?
Aqueous solutions of volatile materials used as flavouring agents. They also have therapeutic value e.g. Concentrated peppermint and anise water can be used as carminatives
69
Why can't a pycnometer measure the density of syrup?
Syrup is too thick, so will not go up the capillary tube properly. Density needs to be determined by optical rotation

Pharm303 (15 decks)

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