Mixing

Question 1

Why is mixing important

Answer 1

Its a critical step in the manufacture of medicines required to ensure even distribution of components.

Question 2

How do we define a homogenous mixture

Answer 2

A particle system in which the concentrations of all constituents are uniform throughou

Question 3

What are the 4 reasons why we must mix medicines effectively

Answer 3

To ensure the quality of pharmaceutical products (essential quality criteria for the mixing process is typically that variations of ±5% with respect to the target mixture values are within the acceptance range. )
Provide an even distribution of active components and other ingredients
Guarantee the drug is released at the desired rate
Give an even appearance to the dosage form

Question 4

What parameters are used to monitor how efffective a mixing process is and why do we use these ones

Answer 4

The Degree of mixing –used to understand/follow the mixing process

The Efficiency of the mixer and the time necessary to achieve the required degree of mixing –this could inform on the possibility to change the process parameters, or the mixer for example.

The Components and their properties, making sure that these have not changed/degraded during the process.

Question 5

How do we decide what mixers to use for specific formulations

Answer 5

To design an efficient mix, it is first essential to identify the components to be mixed and assess their properties. These would have a direct impact on the selection of the type of mixer and the working parameters to be used.We will cover in the next slides which are the

Question 6

Define the powder based on the following particle sizes:

>350microns
<10microns
50-100microns
10-50microns
100-350microns

Answer 6

coarse powder
micronised powder
fine powder
very fine powder
medium/fine powder

Question 7

Why are fine and very fine powders prefered for mixing

Answer 7

fine and very fine powders (particles in the range of 25-50 micron) are preferred for mixing because of their good flow and packing properties.

Question 8

Why are particles <15 microns not favoured for mixing

Answer 8

particles < 15 microns generally tend to aggregate, impairing the quality of mix and even distribution/composition of a powder.

Question 9

What is the difference between positive mixtures and negative mixtures

Answer 9

Positive mixtures do not create any issue in the manufacturing process (components mix spontaneously and irreversibly by diffusion), negative mixture instead require a higher degree of mixing efficiency (components separate - the viscocity of the solution slows down the separation process (creams, ointments))

Question 10

What is a neutral mixture

Answer 10

Neutral mixture are static in behavior - the have no tendancy to mix or separate spontaneously. They tend to de-mix only if an external energy input is given to the mixture e.g. powder segregation

Question 11

What is a random mixture

Answer 11

In this type of mixture, the probability of particles to be in the desired mix is equal to the proportion of particles present in the mix. In a completely random mixture, particles are randomly dispersed among the particles of the other components. The probability of finding a particle of any given component in the completely random mixture is identical in every location.
It is also defined as “the perfect mix”

Question 12

What is an ordered mix

Answer 12

Ordered mixing is achieved when particles are not independent, and smaller particles interact with a larger carrier determining the degree of the ordered mix. Surface interaction and attractive forces hold the particles at the ‘adsorption site’ with forces greater than the gravitational forces

Question 13

How are the particles arranged in an ordered mixture

Answer 13

Individual particles of a given component, whose number is equal to or less than the other component, are evenly dispersed in the matrix of the latter, and the distance between the particles of the former is identical in all directions.

Question 14

Is a mixture with a regular spiral pattern ideally ordered?

Answer 14

Not every mixture with a regular spatial pattern is necessarily an ideally ordered mixture because a striated arrangement of the components represents a regular pattern but it does not always correspond to the highest degree of mixture attainable

Question 15

What is the standard deviation or varience in a sample of an ideally ordered mixture

Answer 15

, the standard deviation or variance of the sample concentrations must be zero or nearly zero in such a mixture. The degree of homogeneity measured on the basis of any mixing index must be the highes

Question 16

How do you achieve a perfect mix

Answer 16

Perfect mix is achieved and controlled when particles have almostsimilar properties, like density, particle size, particle shape, surface charge.

Question 17

Why is this dificult to achieve in practice

Answer 17

Mixtures are not generally composed by components that interact and form such perfect mix, hence a random mix is likely to be obtained

Question 18

Why do random mixes, when tested, return different quality information

Answer 18

The composition within a random mixture can vary to a certain extent from site to site and from experiment to experiment. The extent of this inherent variation depends on the overall composition of the mixture and also on the “sample size” with which the local concentrations of the constituents are determined

Question 19

When testing samples of mixed drugs, how can we determine the quality of the formulation given as it can be so variable

Answer 19

Remember that ideally, the highest number of particles per selected scale of scrutiny are tested, the better is the representation of the mix. This would put you in a good position to accept/reject the mixed batch and the mixing process, as well as provide feedback to improve the mixing process.