solid dosage forms: powders and granules Flashcards
(119 cards)
1
Q
powder properties: (powder technology) (3)
A
particle form
particle shape
particle size
-particle size analysis, reductions and separation methds
2
Q
bulk powder properties (3)
A
density
-particle density
pwder density or bulk density
porosity
specific SA
3
Q
other properties? (3)
A
powder flow
mixing and segregation
powder and granules as dosage forms
4
Q
griseofulvin particle size (2 kinds)
A
microsize
- 4 micrometer particle size
- dose 500mg to 1g/day
ultramicrosize
- 1 micrometer PS
- 375 to 750mg/day
5
Q
relative absorption of griseofulvin particle sizes
A
ultramicrosize griseofulvin absorption is almost complete
microsize griseofulvin is variable
-27-72% of an oral dose
6
Q
powder defn
-size
A
single solid or mix of solids in a finely divided state
sizes smaller than 1000micrometers
7
Q
granule def’n
-sizes
A
solid dosage form composed of agglomerations of smaller particles
sizes 0.2mm to 4mm
8
Q
what has better flow granules or particles
A
granules usually used to inc particle size to flow better
9
Q
powders and granules can be used as (2)
A
solid dosage forms
intermediates in the production of other dosage forms (tablets or capsules)
10
Q
solids can have 3 forms
A
crystalline
amorphus
polymeric
11
Q
crystalline solids
- defn
- 3 subtypes
A
regular geometric arrangement or lattice repeated in all 3 dimensions (unit cell)
polymorphs, hydrates/solvates, salts/cocrystals
12
Q
amorphous solids
- defn
- subtypes
A
irregular geometric arrangement
amophous
amorphous dispersions
13
Q
polymeric solid
-def’n
A
large molecule made up of many small repeating units (monomers)
14
Q
particle form: polymorphism
A
different packing pattern of the same molecule, giving different crystal forms
15
Q
metastable polymorphism
A
metastable (thermodynamically unstable) fomr s will convert to ONE truly stable form over time (monotropic polymorphism
16
Q
particle form: polymorphism
-if more stable forms exist
A
if more stable forms exist, and reversible transformation is called enantiotropic polymorphism
17
Q
particle form: polymorphism
-how characterize
A
x-ray diffraction
thermal analysis (differential scanning calorimetry or DSC; thermogravimetric analysis or TGA_, spectroscopy
18
Q
particle form: polymorphism
- what changes between polymorphs
A
changes in pysiochemical properties
-MP, dissolution rate, bioavailability, stability
19
Q
what packing arrangement has more energy to dissolve
A
tighter packing arrangement requires more E to dissolve
20
Q
why use a metastable form with lower MP
risk?
A
-lower MP = weak lattice = more soluble = faster dissolution rate
RISK
-may revert to stable form
21
Q
particle form: hydrates/solvates
A
entrapment of solvent molecules within crystal lattice
anhydrous crystals are more soluble than the hydrates
22
Q
particle form: salts
A
two ionized molecules within the crystal lattice (drug + counterion)
increased solubility, dissolution rate and bioavailability for poorly soluble drugs
23
Q
particle form: co-crystals
A
crystal that contains more than one component within the crystal lattice (drug + co-former)
netrual cpds with non-ionic interactions (H+ bonds, VDW, etc)
24
Q
particle form: amorphous solids
-order
A
not packed in a defined order
25
particle form: amorphous solids
| -glass transition
have glass transition T (Tg)
- at low T (below Tg): material is brittle or glassy
- at higher T (above Tg): material is rubbery
26
particle form: amorphous solids
| -how produce
produced by fast solidification process or by breakage of crystals
ex. milling
27
particle form: amorphous solids
| -used in what preparations
solid amorphous dispersions and co-amorphous
28
particle shapes (6)
acicular
columnar
flake
plate
lath
equant
29
what is crystal habit
external shape of a crystal
| -refer to particle shape
30
particle size: micrometrics
science and tech of small particles
| -particle size measurements, size distribution and packing arrangements
31
particle size: effect on dissolution rate
micronized drugs can inc rate and bioavailability
32
particle size: dose uniformity
uniform distribution of API in powder miz to ensure dose to dose content uniformity
33
particle size: control of particle suspension
control the suspension of particles dispersed in a vehicle
34
particle size: physical stability
improve physical stability, smoothness and appearance of semisolids
ex. creams, oints etc
35
particle size: MOST IMPORTANT for powders and granules (3)
affect flow and packing properties
facilitate drying
improve pen (in lungs) of particles used in inhalation products
36
particle size: dimensions
particles are 3D objects
37
particle size: what do MOST measurements assume wrt particles shape
most measurements assume that the material is sphericle
38
it is impossible to describe a particle using a single number (t/f)
true
| -SO use particle size distribtions
39
howparticle size: how may they be dispersed
particle size of a sample is heterogenous or polydispersed
40
look at ferets diameter and martins diameter and projected area diameter and length and width
asldkjfasl;kdjfuhireruhieerhiulerhiueihur
41
particle size distributions
- cumulative distribution curve
- expressions for mean diameter based on what
cumulative distribution curve
- plot frequency vs particle size
expressions for mean diameter based on what
-diameter
Dd is mean diameter based on particle diameter
-surface area
Ds is mean diameter based on particle surface
-volume
Dv is mean diameter based on particle volume
42
broad cumulative distribution curve
lots different particle sizes
43
what shape cumulative distribution curve do you want
sharp curve, less diffs in particle size
44
look at graphs page 18
asdjfh
45
particle size: coarse
mesh opening size (microns)
- >355
mesh size number
20-40
46
particle size: moderately fine
mesh opening size (microns)
- 180-355
mesh size number
- 40-80
47
particle size: fine
mesh opening size (microns)
- 125-180
mesh size number
80-120
48
particle size: very fine
mesh opening size (microns)
- greater than or equal to 125
mesh size number
- 120-200
49
how do you determine particle size distribution (5)
1) microscopy
2) sieving
3) laser light scattering
4) sedimentation
5) electrical zone sensing (coulter counter)
50
Microscopy
optical microscope
scanning electrom microscope (SEM)
transmission electron microscopy (TEM)
dynamic image analyses
DEFINITIONS ON PP
51
mean particle diameter (dave)
(sum of midsize*number of particles in ea size group) / (sum of number particles in ea size group)
52
sieving method (2)
- def'n
- range
predetermined weight of dry powder passed through wire mesh screens
- ea screen has openings of different sizes
- weight of powder retained on each sieve is measured
range: ~40 micrometers to 5mm (dpnding on sieve sizes
53
mesh sizes (sieving)
mesh number is the number of openings per linear inch
54
large sieve number separates
small particles
55
small sieve number
separates large/coarse particles
56
sieving method: calculate diameter ave
diameter ave = [(%retained)(ave size)] / 100
57
sieving method advantages (2)
simple cheap easy to interpret
technique is well adapted for bulk materials
-large amount of material can be loaded into sieve trays
58
sieving method disadvantages (2)
-smallest particle sieve size (400 mesh) is 38 micrometers
amount of E used to sieve the sample is empirically determined
- over-energetic sieving causes attrition of the particles
- insufficient E fails to break down loose agglomerates
59
light scattering (2)
includes: laser diffraction and dynamic light scattering
particle size is determined by the angle and intensity of scattered light reaching the sensor
60
light scattering can be used to determine what
determine much smaller particle sizes
61
sedimentation method (3)
- def'n
- assumption/parameters
refer to the settling of a single particle in a liquid medium under the influence of gravitational and centrifugal forces
assumes particles are spherical, the particle [ ] is dilute (max2%) and their sedimentation is unaffected by interaction between particles
diameters determined from stokes law
62
pp slide 28 stokes law
asdfasdfasdf
63
sedimentation method example: andreasen pipette (4)
samples are mized with liquid to form a suspension and placed into the andreasen pipette
mixture is stirred by shaking pipette and left to rest for certain period of time
10mL of sus is collected from a position 200mm below surface of sus
weight of solid obtained after drying sample,
-used to calc the diameter according to the stokes equation
64
what particle size sediments faster
larger
65
electrical sensing zone method (coulter counter) (2)
particle suspended in conducting liquid that passes through small orifice surrounded by electrodes and measures a change in the electrical signal proportional to the volume of the particle
measure volume of particles
66
powder production (3)
pptation and crystallization
- can lead to diff polymorphs depending on conditions
spray drying and freeze drying
-allows for control over size, shape, composition, of particles
communition
-(particle size reduction)
+often start with large particle size and break down by milling
67
Mechanism of size reduction: powder comminution
-aplication of external forces (mechanical) as a way of decreasing cohesion between powder particles
based on crack propagation
-material breaks along cracks so most effective size reduction would be to focus force on cracks
only 2% of force fractures the material
-remaining E is distributed in other processes (shit ton listed in lecture)
68
comminution equipmetn (3)
coarse crushers
- jaw, gyratory, roll and impact crushers
- not used in pharmaceutical industry
intermediate grinders
- rotary cutters, disk, hammer, roller, chaser mills
- produces particles between 20 and 200 mesh
fine grinding mills
-ball, pin, hammer, colloid, fluid-E mills (or air-jet mill)
69
what generates more heat during comminution
smaller particle size product
70
Fine grinding mills
ball mill
- as rotates, balls rotate and fall break down particles
- ball type det particle size
- contamination probs bc need clean ea ball
fluid energy mill or air jet mills
- mostly used for ground powder inhalers
- produces v fine powders
- air jets, as spin air collides with particles and breaks down
- good for heat labile bc air is cooling
71
comminution equipment small scale (3)
trituration
pulverization by intervention
levigation (use liquid to triturate)
72
bulk density properties: density
| 4 types
true density
- ratio of mass of particle to its actual volume (excludes pores and gaps
particle density
-ratio of mass of particle to volume of particle including intraparticulate pores, excluding gaps
bulk density
-ratio of powder bed mass to volume of loose powder bed, includes pore and gap volume
tapped density
-ratio of powder bed mass to volume of tapped (or compacted) powder bed, includes pore and gap volumes
73
bulk density properties: density, what is void
void
-pores (intraparticulate air volume)
-gaps (interparticulate air volume
74
bulk density properties: porosity (% of void space)
| 3
volume of the pore interor and gap space in a powder
indicate the packing efficiency of a powder
measured by gas absoption method or mercury porosimetry
ON PP IS CALC
75
bulk density properties: specific SA
determined by particle size and porosity. provides info on void space on particle surface (pores) or within an agglomerate
measured by gas absorption or gas permeability procedures
76
powder flowability definition (2)
ease with which a powder will flow under a specified set of conditions
complex phenomenon, referring to both physical properties affecting powder flow and the equipment required for handling, storage, and processing
77
importance of powder flow (4)
uniform feed from storage containers or hoppers into the feed mechs of tableting or capsule-filling equipment
reproducible filling of tablet dies and capsule dosetors
uneven powder flow can result in excess entrapped air within powders affecting compression
cause lubrication problems and increase dust contamination risks during powder transfer
78
factors affecting powder flow
adhesion/cohesion
size, shape, density
79
adhesion
tendency of dissimilar particles or surfaces to cling to one another
mechanical, chemical, dispersive, electrostatic, diffusive etc
80
cohesion
tendency of similar or identical particles/surfaces to cling to one another
intrinsic property of a substance that is caused by the shape and structure of its molecule
81
alteration of particle size
| -ranges and flow
250-2000 micrometers (flow freely
75-250micrometers (may cause flow problems
<50micrometers (irregular flow or no flow (mainly due to VDW florces))
82
alteration of particle shape
| -what shapes flow better
spheres flow better than needles
83
Bulk density
flowability can be estimated from bulk density of powder using a tapped density device
84
bulk density: hausner ratio
hausener ratio = ptapped/pbulk
85
bulk density: carr's index
CI = [ptapped-pbulk]/ptapped * 100
86
slide 45 table of flow character and carr index/ hausner ratio
87
high carr index
poor flow
88
low carr index
good flow
89
hausner ratio low
good flow
90
hausner ratio high
poor flow
91
angle of repose (2)
angle between the free surface of the powder body and the horizontal plane when poured from a funnel
simple method, poor reproducibility
92
angle of repose
| -flow indicators
flatter cone = better flow
sharp peak = poorer flow
93
flow through an orifice (2)
direct method
-measure rate of powder discharging from the hopper or a funnel
flow rate calculated by dividing mass of powder by total time taken for powder to flow out from funnel
94
shear cell (2)
more reproducible results, time consuming
bulk solid sample loaded in container or "cell", load is applied and the powder bed is sheared until a uniform consolidation (constant shear stress value)
95
powder mixing
operation that serves to make two or more components uniformly distributed in the powder bed
96
mechanisms of powder mixing
diffusion
convection
shear
97
mechanisms of powder mixing: diffusion
when powder bed is forced move/flow, it dilates
| increase air space btwn particles
98
mechanisms of powder mixing: convection
transfer of large groups of particle from one part of powder bed to another
ex. mizer blade moves through mix, tumbling mizers
99
mechanisms of powder mixing: shear
layer of material moves/flows over another layer
| ex. tumbling mixers
100
generally diffusion convection and shear are used in a mixing process of powders (t/f)
true
101
powder demixing (segregation)
separation of drug from other powder components
102
factors affecting segregation: particle size
particle size = main cause of segregation
-smaller particles fall into spaces btwn larger (percolation segregation)
-larger particles move greater distances then smaller particles (trajectory segregation)
during mixing dust is blown upwards, when mixing stops, dust sediments on top of caorser particles (elutriation segregation or "dusting out")
103
factors affecting segregation: particle density and particle shape
denser particles move down
spherical particles easier to mix, but tend to segregate more
104
how to minimize segregation (6)
1) select similar particle size range for drugs and excipients
2) control crystallization of drugs and excipients to give same particle shape
3) choose excipients with same density as APIs
4) granulation of powder mix
5) reduce vibration after mixing
6) production of an ordered mix
105
ordered mix
micronized powders absorbed on surface of larger carrier particle
-used in antibiotic formulations and dry powder inhalers
micronized powders dont flow well by themselves so absorbed to surface of larger carrier
106
mixing equipment (3)
mortar and pestle
- most common, small scale
- important to mix by geometric dilution steps
- combines comminution and mixing (shear)
tumbling mixers/blenders
- V-mixers, rotating cube, cone, etc
- mixes powders or granules with good flowability
shear and forced-circulation mixer
- blade mixers, planetary mizers, high-speed mizers, ribbon agitator mizer, nauta mizer
- high speed mizer can be used easily break up agglomerates, not suitable for materials that fracture easily
- provides more complete mizing
107
powders/granules as a dosage form: advantages (5)
- more chemically stable than liquids
- easier to swallow than capsules and tablets
- larger doses can be dispensed
- faster dissolution and absorption rates (higher SA)
- can be applied to many body cavities such as ears, nose, throat
108
powders/granules as a dosage form: disadvantages
-less conventient to carry
hard to mask unpleasant tastes
not suitable for potent drug with low dose
not suitable for drugs that are inactivated or cause dmg to stomach
109
types of powders and granules (5)
- bulk powders
- divided powders
- powders and granules for oral solution or suspension and for injection
- dusting powders
- inhalation powders and nasal powders
110
Bulk powders
packed in bulk containers
| -nonpotent substances with large doses
111
problem with bulk powders
inaccuracy of dosing
112
bulk powders: effervescent powders/granules
- special class of bulk powders
- consist of API in combo with effervescent salt pairs
- help cover unpleasant or bitter taste
113
effervescent granule ratio
1 (citric acid) : 2 (tartaric acid) : 3.4 (sodium bicarbonate)
114
divided powders or granules: bulk powders where individual doses are packaged separately
traditionally packed in paper, now replaced foil and plastic laminats
115
divided powders or granules: powders and granules for oral solution or suspension and for injections (2)
reconstituted just prior to administration by adding water or sterile water for injections
drugs with physical and chemical stability problems that need to be dispensed in the dry state
ex. antibiotics
116
dusting powders: use
designed for external use
| -act as therapeutic, lubricant, or protective
117
dusting powders: how dispensed
usually dispensed in relatively fine state (micronized) to increase efficacy and decrease irritation
-should be passed through 100-200 mesch sieve and should have excellent flowability
118
dusting powders: how packed
packed in with perforated lid to allow powders to be dusted to the effective area
119
Inhalation powders and nasal powders (3)
1) insufflator
2) why insufflator use decline
3) DPI
1) insufflations are fine powders of drugs dosed into the nose, ear, or throat by the use of an insufflator
2) use of conventional insufflators has declined due to poor patient complianse and dose non-uniformity
3) dry powder inhalers (DPIs) have replaced most traditional insufflation dosage forms
