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MP221 Normal Function of the GI Tract > Lecture 11 > Flashcards

Lecture 11 Flashcards

1
Q

What is a pharmaceutical solution ?

A

It is a liquid system.
It is a one-phase system all the ingredients are dispersed evenly at the molecular level.
They are optically clear.

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2
Q

How is a solution prepared ?

A

Drug is added as a solid to the vehicle (solvent, most commonly water).
Drug dissolves completely.
Drug is in solution.

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3
Q

What are the other components added to make up a formulations ?

A

Preservatives, buffers, flavours, etc.

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4
Q

What is a pharmaceutical suspension ?

A

It is a dispersion of solid materials, generally the drug, in a liquid phase.
Also a liquid system.
However, the solid is not dissolved in the liquid phase - the drug remains as solid particles.
Not optically clear.

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5
Q

How are suspensions classed ?

A

They are classed by particle size.
>1mcm - coarse dispersion.
<1mcm - colloidal dispersion.

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6
Q

What is the typical suspension particle size ?

A

0.1-10 mcm

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7
Q

What are examples of suspensions ?

A

Gaviscon, kaoline mixture, ampicillin suspension, insulin zinc suspension.

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8
Q

Why are suspensions used ?

A

It is because many drugs have a low solubility in the continuous phase and therefore form suspensions.
Liquid form is sometimes easier to take than a solid dosage form.
Drugs may have an unpleasant taste in the soluble form and so can be made into suspension to mask the taste and make the drug more palatable.
Freshly prepared suspension means a longer shelf life.
Modification of drug release form the system especially for injections.
Faster onset of action because the drug is already in divided form in the continuous phase and so optimal dissolution in the GI tract so increased absorption.

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9
Q

Why would you need to shake the suspension bottle before use ?

A

To allows equal distribution.

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10
Q

What do solid-particle interactions do ?

A

They determine the behaviour of the suspension.

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11
Q

What is the most common liquid phase ?

A

Water.

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12
Q

What is the particle ?

A

It is typically the drug.

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13
Q

What could be the reason for some material to not dissolve in the liquid phase ?

A

They may require some chemical similarities between the material and the liquid phase.

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14
Q

Why are many modern drugs hydrophobic ?

A

This is because the receptor that the drug must target is also hydrophobic and because they have low solubility in water/aqueous solutions which is why they are in suspension.

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15
Q

What happens when the drug particle is dispersed in water ?

A

The drug particle will acquire a charge.

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16
Q

What happens when a particle acquires a charge ?

A

An electrical double layer will be formed around the particle which is due to the ionisation of the water and not the drug.

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17
Q

What happens at the surface of the particle ?

A

Water is split into hydrogen and hydroxide ions.

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18
Q

What happens to the hydrogen and hydroxide ions that are split at the surface of the particle ?

A

The hydroxide ions stay at the surface of the particle and the hydrogen ions will travel into the continuous phase, into the solution.

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19
Q

What happens to the hydrogen ion as it travels into the solution ?

A

The hydrogen ion combines with the water.

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20
Q

From the surface of the particle to the continuous phase, there is…

A

… a gradient of charges, the negative charge on the particle surface is fixed and the positive charge in the solution diffuses.

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21
Q

Why does the particle have a negative charge ?

A

This is because the hydroxide ions which carry a negative charge collect on the surface of the particle which gives the particle its apparent negative charge.

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22
Q

Why do most particles in water acquire a negative charge ?

A

This is due to the preferential absorption of hydroxide ions.

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23
Q

What are factors that affect the electrical double layer ?

A

Excipients change the behaviour of solid particles in suspension (fixed and/or diffuse layer).

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24
Q

What happens if a low concentration of ionic material is added to the solution ?

A

These ionic materials will be found in the diffuse layer.

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25
Q

What happens is a high concentration of ionic material is added o the solution ?

A

This will impact both the fixed and the diffuse layer.

26
Q

How can suspensions be manipulated ?

A

Through the use of ions.

27
Q

What can ions impact ?

A

They can impact the electrical double layer.

28
Q

What is the DVLO theory ?

A

It is the behaviour of two particles in suspension.

29
Q

What is the total potential energy ?

A

Vt = Va + Vr

30
Q

What are the interaction between the particles ?

A

They are additive (Vt).

31
Q

What are repulsive forces ?

A

The osmotic effects due to overlap of the diffuse parts of the electrical double layer.

32
Q

What are attractive forces ?

A

VDW universal forces of attraction.

33
Q

What does the DVLO theory allow ?

A

It allows the prediction of suspensions i.e. whether the particles in the suspension will coalesce and settle or remain dispersed which is important for dose reproducibility.

34
Q

In the primary minimum, why are the attractive forces greater than the kinetic energy ?

A

This is because at this point, the particle are still individual but come together to form a floccule.

35
Q

What is coagulation ?

A

When particles collide and form larger particles that cannot be broken up.
This undesirable for pharmaceutical suspensions.

36
Q

What can lead to coagulation ?

A

When the attractive forces grow greater as the particles move closer together.

37
Q

What is flocculation ?

A

Loosely attracted particles but still independent.

38
Q

Why are the repulsive forces stronger than the attractive forces in the primary maximum ?

A

This is because the particles exhibit deflocculation.

39
Q

What is deflocculation ?

A

This is when the particles remain separated.

40
Q

What happens if energy is imported into particles in a deflocculated state ?

A

The particles start to move, maybe due to a temperature increase.

41
Q

What needs to continue for the particles to move apart and total potential energy to decrease ?

A

The total potential energy needs to remain greater than the kinetic energy.

42
Q

What happens if there is sufficient kinetic energy ?

A

The repulsive barrier will be overcome and then the particles will move closer together.

43
Q

In the secondary minimum, which is greater, the attractive forces or the repulsive forces ?

A

The attractive forces are greater then the repulsive forces.

44
Q

What is the desired state for pharmaceutical suspensions ?

A

To have the particles show limited attraction to each other and behave as floccules.
As the total potential energy increases, the particles will experience weak repulsive forces once forced apart.

45
Q

What happens when the total potential energy is greater than kinetic energy ?

A

The particle move closer together but will not collide and coalesce as the total potential energy is small.

46
Q

What particle behaviours in suspensions must be controlled ?

A

Constants - particulate material i.e. the drug, continuous phase i.e. water because of formulation for oral administration.
Variables - distance between the particles which is partly dependent on temperature kinetic energy particle concentration, surface potential of particles which can be modified by absorbing materials onto the particle, ionic strength, radium of particles e.g. Va Vr Vt which are directly proportional to particle size.

47
Q

What happens if the particle size is reduced ?

A

The primary minimum and primary maximum will also be reduced.

48
Q

What happens if there is a change in particle size ?

A

This would influence the kinetic energy which would impact the overall performance.

49
Q

What impacts inter-particle distance ?

A

The particle movement within suspensions which then impacts Va, Vr and Vt.

50
Q

What is Brownian motion ?

A

It is the diffusion of particles to improve dosage uniformity.
It is relevant for particles between 1-2 mcm in size.

51
Q

Why is Brownian motion important ?

A

It is important for deflocculated suspensions of particles in submicrometre range.

52
Q

What can be used to describe gravitational sedimentation ?

A

Stoke’s equation.

53
Q

What is particle movement ?

A

The distance between particles.

54
Q

The steps in sedimentation

A

Step 1 - deflocculation - secondary minimum.
Step 2 - flocculation - primary maximum.
Step 3 - deflocculation - primary minimum.
Step 4 - coagulation, irreversible.

55
Q

What can influence gravitational sedimentation ?

A

Density of the particle, radius of the particle, density of the medium, viscosity of the medium and temperature although it is not really used.

56
Q

What is the desired pharmaceutical suspension ?

A

Considers the speed of sedimentation and reversibility.

Requires balance of opposing factors.

57
Q

What happens if there is a deflocculated system with no/minimal sedimentation ?

A

There is a greater density and greater viscosity of continuous phase.

58
Q

What happens if the suspension is too viscous ?

A

It will be difficult to pour/measure a dose.

59
Q

What happens if there is a change in particular dispersion pattern ?

A

This causes an impact on the primary minimum and coagulation, which cannot be changed and is considered a product failure.

60
Q

Why is it easy to disperse and pour/measure a dose in a flocculated system ?

A

This is because the particle are independent and may to break up the loose floccules.

MP221 Normal Function of the GI Tract (13 decks)

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