Powder Technology

Which process is the main barriers to protect the patient?

Quality control of solid dosage forms

1 of 97

What is a powder?

The physical form of a material, that is a dry substance composed of finely divided particles

2 of 97

What is a pharmaceutical powder?

A solid dosage form comprising of a large number of finely divided solid particles of drugs or mixture of drugs and excipients

3 of 97

What are the two types of pharmaceutical powder?

A type of pharmaceutical preparation that is, a medicated powder intended for internal (e.g. oral powder) or external (e.g. topical powder) use

4 of 97

Give two examples of an internal powder

Lemsip and baby teething powder

5 of 97

Give an example of an external powder

Baby powder

6 of 97

What are the three main processes which involve powders in the formulation process?

Powder processing (milling and characterisation), dosage form specific manufacture, quality control characterisation

7 of 97

What is quality control?

Refers to a procedure or set of steps taken during manufacturing of a product to ensure that it meets pharmacopoeia requirements and that the product is reproducible

8 of 97

How are solid dosage forms manufactured (5)?

Target Product Profile (TPP), physicochemical characterisation of API and excipients, powder processing (milling/characterisation), dosage form specific manufacture, quality control characterisation

9 of 97

State the features of Target Product Profile (4)

Phase I/II, phase II, market, product life cycle management

10 of 97

State the features of physicochemical characterisation of API and excipients (3)

Solid state, chemical stability, particle size

11 of 97

State the features of powder processing (3)

Milling, mixing, flowability

12 of 97

State the features of dosage form specific manufacture (6)

Powders, granules, pellets, capsules, tablets, specialised systems

13 of 97

State the features of quality control characterisation (4)

Uniform content, uniform weight, dosage form specific QC parameters, storage stability

14 of 97

Give examples of powders in pharmacy practice (7)

Diamorphine hydrochloride, citric acid, symbicort turbohaler, Zineryt, Beechams, Phenoxymethyl-penicillin, infants' powders

15 of 97

Why are powders interesting (2)?

Need to have knowledge of how pharmaceutical powders behave from raw material dispensing/blending/storage transfer to final dosage form. Before use in preparation, solid materials are characterised to determine chemical/physical features

16 of 97

What is powder flowability and mixability?

The ability of the powder to flow

17 of 97

Is flow behaviour multidimensional?

Yes - depends on many factors

18 of 97

What are the uniformity dosage units (2)?

Content uniformity and mass/weight variation

19 of 97

What is content uniformity?

Quantify the individual content of the active ingredient per dosage form e.g. tablet/capsule

20 of 97

What is mass/weight variation?

Quantify the individual mass/weight of the active ingredient per dosage form e.g. tablet/capsule

21 of 97

What is powder compressibility?

The ability of a powder to decrease in volume under pressure

22 of 97

What is powder compactability?

The ability of a powder to be compressed into a tablet of a specified strength

23 of 97

What is IVIVC?

In vitro in vivo correlation (within the glass within the living)

24 of 97

What happens to a tablet in vivo?

The tablet is broken down to granules of a specific size

25 of 97

What do in vitro disintegration studies involve (1) ?

Observe the time required for a dosage form to break up in to granules of specified size (or smaller) under specified conditions

26 of 97

What do in vitro dissolution studies involve (3)?

Drug release studies, assess batch-to-batch consistency of solid dosage forms (e.g. tablets), predict safety and efficacy of a drug product in vivo

27 of 97

What are the three states of matter relevant to pharmaceutical science?

Solid, liquid and gas

28 of 97

Describe features of a solid

Molecules arranged in regular repeating patterns, held firmly in place but can vibrate within a limited area, low energy (e.g. powder)

29 of 97

Describe features of a liquid

Molecules flow easily around one another. They are kept from flying apart by attractive forces between them. Liquids take up the shape of their containers. Medium energy (e.g. syrup)

30 of 97

Describe features of a gas

Molecules fly in all directions at great speeds. They are so far apart that attractive forces between them are insignificant. High energy (e.g. O2, air, N2)

31 of 97

Why is a solid the most common dosage form?

Solids are more stable in liquids or gases. Active Pharmaceutical Ingredients (APIs) are usually manufactured/transported/stored as solid, most drugs marketed as solid dosage forms, cheaper to manufacture

32 of 97

What is the state of API for: tablet, capsule, powder/granule, ointment/cream/gel, transdermal, suppository, solution, dispersion?

Solid, solid/liquid, solid, solid, solid, solid, liquid, solid/liquid

33 of 97

What are the two main classifications of solids (based on molecular packing)?

Amorphous and crystalline

34 of 97

State the sub-sections of a crystalline solid (4) (3)

Solvate, polymorphs, salt form, co-crystal. Conformational, concomitant, polymorphic solvates

35 of 97

What type of order is in a crystalline solid?

Long range molecular order

36 of 97

What are the two ways to form a crystalline solid?

Cool slowly below Tm. Crystal growth from supersaturated solution (nucleation and growth)

37 of 97

What is supersaturation?

A state of a solution containing more of dissolved material than could be dissolved by solvent under normal circumstances. It can also refer to a vapour of a compound that has a higher (partial) pressure than the vapour pressure of that compound

38 of 97

What is nucleation?

Initial process occurs in the formation of a crystal from solution/liquid/vapour. Small number of ions/atoms/molecules become arranged in a pattern characteristic of crystalline solid (form site which particles deposit as crystal grows)

39 of 97

What is crystal growth?

A major stage of a crystalline process. Growth followed by either homogeneous or heterogenous nucleation unless a 'seed' crystal purposely added to start growth was already present

40 of 97

Describe crystalline solid transitions

Melt (solid-liquid), melting point Tm breaks up crystal lattice. Freeze (liquid-solid), freezing point Tf builds up crystal lattice

41 of 97

What are polymorphs?

Crystalline forms with the same chemical composition but with different internal structures (>80% of pharmaceutical solids exhibit polymorphs)

42 of 97

What are the three types of polymorphs?

Conformational polymorphs, concomitant polymorphs and polymorphic solvates

43 of 97

What are conformational polymorphs?

The same molecule can adopt different crystal shapes in different crystals due to internal degrees of freedom

44 of 97

What are concomitant polymorphs?

The appearance of two or more polymorphs within the same crystal bath

45 of 97

What are polymorphic solvates?

Occur when a given substance crystallises with different amounts of types of solvent molecules

46 of 97

Give examples of crystalline solids (14)

Diamonds, quartz, sucrose, snowflakes, ceramics, cements, pigments, electronics components, household goods, pharmaceuticals, cosmetics, bones, teeth, shells

47 of 97

What type of order is in an amorphous state?

Short range molecular order

48 of 97

What are the two types of amorphous formation?

Rapid solidification process (rapid precipitation/quenching of melt). Extreme processes (freeze/spray drying, mechanical/chemical stresses e.g. grinding, milling, wet granulation)

49 of 97

Can a physical form of a drug be partially amorphous and partially crystalline?

Yes

50 of 97

What is Tg?

Glass transition temperature. Reversible transition in amorphous materials (or in amorphous regions within semi-crystalline materials) from hard/brittle glass state into viscous/rubber state as temperature is increased

51 of 97

Describe amorphous solid transitions

Below Tg, glassy state (no mobility of molecules). Above Tg, rubbery state (mobility of molecules)

52 of 97

Give examples of amorphous solids (8)

Window glass, amorphous ice, boiled sweets, rubber polymers. Pharmaceutical: proteins, peptides, some sugars and polymers

53 of 97

What is the ideal shape of a particle?

A solid sphere (one dimension, radius, describes size/shape/SA/volume). Solid geometrical particles (two dimensions required to describe size/shape/SA/volume)

54 of 97

What is the shape of particles in reality?

Solid irregular particles (size/shape can only be approximated, SA/volume can be measured). Porous irregular particles (size/shape/SA/volume can only be approximated)

55 of 97

What does porous mean?

Possessing or full of pores (holes), permeable to gases and/or fluids

56 of 97

What are the four types of particle shape terminology?

Acicular (needle-shaped), angular (sharp edged/roughly polyhedral shaped). Dendritic (branched crystalline shape, natural fractal pattern), fibrous (thread-like)

57 of 97

Where are dendritic particle shapes seen?

In snowflake formation and frost patterns on a window

58 of 97

What are the three factors which can influence particle shape?

Content uniformity, powder flowability, powder mixability

59 of 97

What are the three types of particle shape?

Spherical particles (good flowability/easy mixing). Elongated, needle-like particles (tendency to interlock, higher SA). Irregular particles (cohesive effects due to greater SA, increase likelihood of dusting out)

60 of 97

Particle size influence many properties of particulate materials and is a valuable indicator of what?

Quality and performance

61 of 97

In the Pharmaceutical Industry, which processes are affected by particle size (4)?

Content uniformity, flow and mixing. Release and dissolution of a drug. Absorption and therapeutic effect. Final dosage form quality

62 of 97

Why is particle size important?

The API composition not uniform. Larger particle size may have caused some unit doses to fail potency specifications. Poor control of particle size led to substandard product (possible overdose in patient)

63 of 97

What does the Noyes-Whitney equation state?

An increase in total surface area leads to an increase in dissolution rate and bioavailability. Smaller particle size leads to greater SA and dissolution rate)

64 of 97

What is surface area?

The surface area of a solid is a measure of the total area that the surface of the object occupies

65 of 97

What is specific surface area per weight unit?

A property of solids defined as the total surface area of a material per unit of mass (m2/kg)

66 of 97

What is specific surface area per volume unit?

A small particle may be best described as matter of a small particle size with an immensely high surface area to volume ratio

67 of 97

What are the two types of data presentation for particle size distribution?

Incremental distribution and cumulative distribution

68 of 97

What does incremental distribution show?

How many particles fall within a given size increment/band

69 of 97

What does cumulative distribution show?

How much material lies above or below a particle size

70 of 97

What do histograms yield a measure of (3)?

Central tendency, distribution model, dispersion

71 of 97

Give four examples of distribution models

Normal (bell curve with one peak). Bimodal (two peaks). Positively skewed (tail on the right). Negatively skewed (tail on the left)

72 of 97

Describe features of normal distribution

Used when an item is subject to random variation. Symmetry about centre. 50% of values less than mean and 50% greater than mean

73 of 97

Give two examples where normal distribution is found in natural systems

Distribution of heights of people is normal. Distribution of tablet weights in a batch is normal

74 of 97

Describe features of dispersion

In a real sample of material there will exist a range of particle sizes spread about the mean. If the range of particle sizes exists it is polydisperse. If particles in sample are all the same size it is monodisperse

75 of 97

Describe features of the D90/D10 ratio

Used by the Pharmaceutical Industry to describe the polydispersity of powders (regardless of the distribution model). In cases of multimodal distributions, it is a useful measure of dispersion. D90/D10 ratio has no units, it is in 2 d.p.

76 of 97

What does a D90/D10 ratio value close to 1.00 indicate?

There is a more narrow dispersion around the median value

77 of 97

What is the arithmetic standard deviation?

The dispersion of values around the mean of a normal population distribution (complete population method)

78 of 97

How is the arithmetic standard deviation modified for random sample method?

Total number of particles minus one

79 of 97

What is the geometric standard deviation?

Formula involves the number of particles in size groups and the total number of particles

80 of 97

What is the Equivalent Spherical Diameter (ESD)?

The ESD of an irregularly shaped object is the diameter of the sphere of an equivalent volume. Equivalent diameter of non-spherical particle = diameter of spherical particle that exhibits identical properties to that of non-spherical particle

81 of 97

Give examples of properties involved when investigating ESD (4)

Aerodynamic, hydrodynamic, optical, electrical

82 of 97

What are the different factors considered in ESD (7)?

Same maximum and minimum length, same weight, same volume, same SA, passes same sieve aperture, same sedimentation rate

83 of 97

Which distribution plot would be used to find the % of powder falling into a specific size (quick information on particle size distribution)?

Incremental plot distribution

84 of 97

Which distribution plot would be used to find the % of powder smaller or larger than a specified size?

Cumulative plot distribution

85 of 97

Describe features of incremental histograms (4)

Reflects distribution of particle sizes. Presents interpretation of particle size distribution. Enables determination of % of particles having equivalent diameters. Allows different particle size distributions to be compared

86 of 97

What does a cumulative undersize graph show?

The relative amount at or below the particular size

87 of 97

What does a cumulative oversize graph show?

The relative amount at or above particular size

88 of 97

What are the two types of model distribution?

Normal (bell curve, continuous) and lognormal (continuous) - provide information about material or processes through which material has passed

89 of 97

In a normal distribution, which statistics are used?

Arithmetic mean and standard deviation

90 of 97

In lognormal distributions, which statistics are used?

Geometric mean and geometric standard deviations

91 of 97

What if a powder shows neither a normal or lognormal distribution?

Many powders will not be milled long enough to show an ideal normal/lognormal distribution model (likely to be multimodal). Mill powder long enough - eventually show log normal distribution (FAD 1)

92 of 97

When is the median used instead of the mean?

Data set contains a small number of outliers (skews mean). Data set contains zero as a value (affects mean). Data set is unimodal/skewed but does not have normal/lognormal distribution. End values of data set not known

93 of 97

What is the Arith. SD?

D50-D16 or D84-D50

94 of 97

What is the Geo.SD?

Square root of D84/D16

95 of 97

How do you calculate the CV%?

SD/mean x 100

96 of 97

What is the CV% (or relative standard deviation) used for?

To compare the degree of variance between multiple sample populations: uniformity of dosage form studies, quality control of tableting equipment

97 of 97

Get Revising

Powder Technology

Other cards in this set

Card 2

Front

Back

Card 3

Front

Back

Card 4

Front

Back

Card 5

Front

Back

Comments

Similar Pharmacy resources:

Other cards in this set

Card 2

Front

Back

Card 3

Front

Back

Card 4

Front

Back

Card 5

Front

Back

Comments

Related discussions on The Student Room

Similar Pharmacy resources: