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Pharmaceutical Technology and Biopharmacy 2 Summary
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- Rijksuniversiteit Groningen (RuG)
Pharmaceutical Technology and Biopharmacy 2
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PHARMACEUTICALTECHNOLOGY AND
BIOPHARMACY II
,Contents
Lecture 1: Physical Chemistry ....................................................................................................................... 4
Rheology ................................................................................................................................................... 4
Newtonian liquids ................................................................................................................................. 4
Non-Newtonian liquids ......................................................................................................................... 8
Thixotropy and Antithixotropy............................................................................................................ 10
Visco-elasticity .................................................................................................................................... 12
Questions and Answers....................................................................................................................... 13
Lecture 2: Surfaces and Interfaces .............................................................................................................. 14
Surface and interfacial tension ............................................................................................................... 14
Pressure difference over curved interface ......................................................................................... 15
Lecture 3 ..................................................................................................................................................... 24
Colloids .................................................................................................................................................... 24
Types of colloids system ..................................................................................................................... 24
Stability aqueous colloidal systems .................................................................................................... 25
Charge of a particle ............................................................................................................................. 26
Suspensions............................................................................................................................................. 31
Sedimentation suspension - HIGH zeta potentia ................................................................................ 31
Sedimentation suspension - LOW zeta potential................................................................................ 32
How to improve stability..................................................................................................................... 32
Emulsions ............................................................................................................................................ 35
Tableting and Tablets .............................................................................................................................. 38
Lecture 4: Introduction ............................................................................................................................... 39
Medication .............................................................................................................................................. 39
Legal status of medicines .................................................................................................................... 40
Lecture 4.2 Basic operations ....................................................................................................................... 46
Basic operations (key issues in all pharmaceutical preparations): ......................................................... 46
Lecture 4.3: Oral liquid preparations .......................................................................................................... 48
Oral liquids .............................................................................................................................................. 48
Target group of oral liquid medication ................................................................................................... 48
Solvents ................................................................................................................................................... 49
Kinds of oral liquid medications .............................................................................................................. 49
, Pharmaceutics ..................................................................................................................................... 49
Biopharmaceutics ............................................................................................................................... 50
Dose of oral liquid ................................................................................................................................... 51
Advantages and disadvantages of oral liquid ......................................................................................... 51
Questions and Answers .......................................................................................................................... 52
Lecture 5: Shelf life (stability) ..................................................................................................................... 53
Chemical stability .................................................................................................................................... 53
Microbiological stability .......................................................................................................................... 55
Physical stability ...................................................................................................................................... 56
Solutions.............................................................................................................................................. 56
Suspensions for oral use ..................................................................................................................... 56
Emulsions for oral use ......................................................................................................................... 57
Disperse systems................................................................................................................................. 58
The Skin ................................................................................................................................................... 58
Layers .................................................................................................................................................. 58
Skin diseases ....................................................................................................................................... 58
Dermatological preparations .............................................................................................................. 60
Lecture 6: .................................................................................................................................................... 64
Rectal administration .............................................................................................................................. 64
Systemic action drugs ......................................................................................................................... 64
Local action ......................................................................................................................................... 64
Diagnostic............................................................................................................................................ 65
Biopharmaceutics rectal ......................................................................................................................... 65
Things to be aware when rectal Biopharmaceutics are used ............................................................. 65
Preparation of suppositories .................................................................................................................. 65
General form ....................................................................................................................................... 65
Preparation of suppositories .................................................................................................................. 67
Kinds of suppositories ......................................................................................................................... 67
Control of suppositories...................................................................................................................... 69
Final remarks suppositories ................................................................................................................ 69
Lecture 7: Sterelity ...................................................................................................................................... 70
D-value .................................................................................................................................................... 71
Z value ..................................................................................................................................................... 74
,Water activity.............................................................................................................................................. 74
Antimicrobial active substances ......................................................................................................... 75
Clean room .............................................................................................................................................. 76
Endotoxins and pyrogens........................................................................................................................ 76
Osmosis ................................................................................................................................................... 77
Division and population growth.............................................................................................................. 79
Sterility and sterility assurance level ...................................................................................................... 79
Questions and Answers .......................................................................................................................... 81
,Lecture 1: Physical Chemistry
Wouter Hinrichs
Rheology
❖ What is Rheology?
➢ Rheology is a description of the flow of matter.
➢ Other definition: the branch of physics that deals with the
deformation and flow of matter, especially the non-Newtonian
flow of liquids and the plastic flow of solids.
Newtonian liquids
❖ Newtonian liquids have certain rules/requirements
❖
➢ What is a shear rate (D)?
▪ shear rate (D) is the change of the flow rate (dv) with the change of the change of
the distance perpendicular to the fixed surface
• s-1
➢ What is the viscosity?
• is a measure of the resistance against flow
Pa*s
1. What is the unit of dynamic viscosity, n?
Pa*s
2. Deduce the unit of dynamic viscosity, n.
• T is the shear stress: the force placed on the liquid
Pa or N*m-2
• Specific for Newtonian liquids is constant
, it means that when we double, for example, the shear stress, it also means that the
shear rate will be doubled.
➢
▪ It goes through the origin
▪ On the X-axes you always put what you place and on the y-axes you read
what you get
➢ Often used unit: poise (in g*cm-1*s-1 = 10-1 Pa*s)
Two extremes
❖ Diameter solute molecule >> Diameter solvent molecule
➢ What is the results of such assumption?
▪ ➔Solute molecule behaves as a particle with respect to solvent molecule
Solution with Non-rotating particle
❖ ➔ increase in viscosity
➢ Why does increase in viscosity take place?
▪ Particle moves uniformly forwards without any other
movement. Liquid behind particle should then move
uniformly as well
• Arrow indicates flow rate
▪ Total length of all arrows is smaller that that without
particle ➔ flow is lower than what you would expect
based on the sheer stress
▪ And it implies that you have to put more shear stress
on the system to get the same flow rates. In other
words, the viscosity is higher than when you have the pure solvents.
Solution with rotating particle
❖ ➔ increase in viscosity
➢ Why does increase in viscosity take place?
▪ Even though the arrow have the same length in both cases yet there is rotation
• Rotation means more energy in the system to have this additional motion of molecules,
of particles in the solution. ➔ increased viscosity
,How to measure viscosity
Capillary viscometer
❖ Steps to measure viscosity using capillary viscometer
1. fill compartment 1 with the liquid we want to investigate.
2. put some pressure on A or B
▪ does not metter since they have the same effect
3. liquid will be transferred to compartment 2
4. relieve the pressure ➔compartment two will empty ➔ measure the time which
it takes for the liquids to come back to compartments one again.
❖ How are measurement determined?
1. factores
▪ Radius capillary (r) (Larger —> flow will decrease)
▪ Length of the capillary (L) (Longer —> Takes more time to be emptied)
▪ Pressure difference over the length of the capillary (∆p) (Heavy liquid —> Higher pressure
➔Empty faster)
▪ Viscosity of the liquid (n)
2.
▪ N= viscosity
▪ C= constant
• How to determine this constant?
Use liquid which you know its viscosity like water; call it liquid 2
Fill the values here
➢
➢ When the viscosity of certain liquid is known ➔ The constant, C, for a given
viscometer can be determined
▪ P= dichtheid
▪ T=time
, • Which what we measure
3. The dynamic viscosity (h2) of a certain (Newtonian) fluid is determined by
means of a capillary viscometer. For this purpose, the flow time of a
(Newtonian) liquid with a known dynamic viscosity (h1) is determined (t1).
Next, the flow time (t2) is determined for the unknown liquid. When can the
formula be use
It is used to determine the constant of liquid 2 by calculation the
viscosity of liquid 2. The viscosity of liquid 2 Is calculated via the same formula
using the values of liquid 1/ Finally n2 is filled in this formula to calculate the
constant of liquid 2
Falling sphere viscometer
❖ What is the Falling sphere viscometer?
➢ we take a very long cylinder and We Fill it with the Liquids of which we want to know the
viscosity. And we take A sphere and we allow the sphere to fall down in the salina through
the Liquids.
➢ What are the factors that act on the falling sphere?
▪ Constant forces
• Gravitational forces (constant, ↓)
• Uplift or Buoyant forces (constant, ↑)
▪ Frictional forces (depends on speed, ↑) (not constant)
• Equilibrium of forces —> Constant speed
• No equilibrium of forces —> the sphere will go faster and faster.
•
➢ How to determine the viscosity?
▪ Pick a point by which the speed of the falling sphere is constant
• here is we take a certain length in the middle of the liquid. We assume then that there is
already constant speed of the falling sphere
, •
dp: Diameter sphere
ps: Density particle
pf: Density fluid
v: Sedimentation speed (Falling speed)
n: (Dynamic) viscosity
Non-Newtonian liquids
❖ Non-Newtonian liquids do not have certain rules/requirements
➢ when you have a very low shear stress below a certain value,
which we call the shears, the yield stress, we do not have flow ➔
when we do not have flow, the viscosity is here infinitely high
➢ what will happen if the shear stress is increased?
▪ the flow increases and increases more than linearly. So it
means that the viscosity decreases.
❖ Note: regarding the viscosity
➢ when we double the shear stress, it doesn't mean automatically
that the shear rate is also doubled.
Plastic flow behavior
❖ When t goes form A’ to B’ the viscosity does not stay the
same
➢ Why does not viscosity stay the same?
▪ This is because Slope in both figures are the
same but they are irrelevant for viscosity
• Viscosity decreases when t increases
Plastic flow of a cross-linked
polymer solution
❖ Cross links are just not covalent bindings
❖ Why does cross linked polymer not solution flow?
➢ Because all polymer chains are connected by cross links ➔ shear stress
<< yield stress
➢ little bit of deformation is possible but no flow is possible.
➢ What would happen if the shear stress is increased?
, ▪
Cross-links are broken ➔ shear stress (increase shear stress) > yield
stress ➔Flow possible
➢ What happens to the viscosity in the case of broken cross-links?
▪ because of the entanglements. The entanglements resist flow
• when the shear stress is further increased the polymer aligned
more ➔ decrease in the viscosity
5. What is the difference between plastic and pseudo-plastic flow? What causes
this difference?
In case of pseudo-plastic flow: when we have a very low shear stress, we still have
flow. So we do not have solid state behavior, but we have very high viscosity. But
viscosity is not infinitely high.
In the case of Plastic flow : Because all polymer chains are connected by cross links
➔ shear stress << yield stress ➔ viscosity is higher in comparison to that of pseudo
plastic flow
Pseudo-plastic flow behavior shear thinning
❖ It is call shear thinning since the solution becomes less viscos
❖ it really looks similar to plastic flow behavior except for the first part of the real gram.
➢ when we have a very low shear stress, we still have flow. So we do not have solid state behavior,
but we have very high viscosity. But viscosity is not infinitely high. So this is the case actually not
starting here on the left side of the slide, but on the right side of the slide.
▪ In other words, this part does not existe in pseudo-plastic flow : no cross links or no gel
▪
Dilatant flow (shear thickening)
❖ It is call shear thickening since the solution becomes increase
viscos
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