topic about powders and granules as pharmaceutical agents,methods of granulation,types of powders,

1. Introduction to Pharmaceutics-1
PCT 221
3rd Semester
)
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2. • Unit-1 Powders and Granules
• Unit-2 Semisolid Dosage Forms
• Unit-3 Emulsions
• Unit-4 Suspensions
• Unit-5 Pharmaceutical Calculations
Total Credit = 3
Assessment = 2CAs(60%) + End of sem. Exam
(40%)
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3. • Recommended Books
1. Pharmaceutical dosage forms and drug delivery systems Ansel
H.C, Popovich
2. Pharmaceutics, The science of dosage form design, M.E
Aulton
3. Remington, The science and practice of Pharmacy Vol-1 & 2
4. Pharmaceutical Calculations by Stocklosa & Ansel
5. Any other handouts / Reference material given to the class
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4. Unit-1
Powders and Granules
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5. Unit contents
1. Powders and granules as dosage forms
2. Special problems in powdered dosage forms
3. Factors affecting drug availability from
powdered dosage forms
4. Package and storage of powders
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6. TOCs
• Basic definitions
• Advantages and disadvantages
• Powders and granules as dosage forms
– (types / Differences)
• Special problems in powdered dosage forms / Solution
• Factors affecting drug availability from Powdered DF
• Packaging and storage
• Particle size and size analysis
• Calculations
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7. Definitions
• Micromeritics:
– Science of small particles
• Powders:
– Is a mixture of finely divided drugs and /or Chemicals in a dry
form
– According to B.P = subdivided solids containing constituent
particles which can range 1.25um – 1.7mm in diameter
– As DF = are formulations in which powdered drug has been
mixed with powdered excipients to produce final formulations
• Eg. Oral powders, Dusting, dentifrices, bulk powders etc
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8. • Granules (Sieve size=4-12)
– Are aggregations of fine particles of powders in a
mass of about spherical shape or
– Consists of powdered particles which have been
aggregated to form a larger particles of about 2-4mm
in diameter
• Can be prepared by
– Dry or
– Wet Granulation techniques
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9. Why we prepare granules when we have powders?
1. To avoid powder segregation,
if the powder is composed of particles with different
dimensions & different densities, a separation
between these particles will occur.
2. To enhance the flow of powder,
Higher flow ability gives better filling of the dies or
containers, during a volumetric dosage.
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10. 3. Granules have higher porosity than powders,
4. To improve the compressibility of powders.
5. The granulation of toxic materials will reduce the
hazard of generation of toxic dust, which may
arise during the handling of the powders.
6. Materials, which are slightly hygroscope, may
adhere & form a cake if stored as a powder.
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11. • Sieve Number
– A number used to designate the size of the Sieve, which
corresponds to the no. of openings per linear inch
• E.g.. Sieve 20 will have 20 openings in 1 linear inch
• Sieve opening
– Its an approximate size of aperture of a given sieve as
given in USP
• E.g. sieve no 20 will have 20 opening per linear inch
and each opening will have an aperture size = 850µm
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12. Some commonly used sieve no
Sieve Number Sieve opening (µm)
20 850
40 425
60 250
80 180
120 125
. .
.. ..
… …
400 38
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13. • Angle of repose (θ = Tan-1 h/r)
– The maximum slope measured in degrees from the
horizon at which loose solid material will remain in
place or
– Angle of repose of a granular powder is the steepest
angle of descent or dip relative to horizontal plan to
which a material can be piled up.
– If θ > 50 unsatisfactory flow
θ = 25 or less than 25 very good flow
properties
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15. • Glidents
– Excipients that increase flow properties of given
material By correcting surface irregularity, reducing
friction or by neutralizing surface charges b/w
particles
• E.g.,
– Mag. Stearate,
– Aerosil (colloidal silicon dioxide),
– Starch,
– Talc
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16. • Geometric mixing/dilution (doubling up method)
– Mixing of ingredients according to order of their
increasing weight/volume in equal proportions
– E.g. Consider the following master formula
• A =10g
• B =50g
• C =40g
• D =90g
• What could be the benefits ?
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17. Powder mixing techniques
• Spatulation
– is the combining of materials (2 or more powders) into a
homogeneous mixture by continuously mixing them
together & smoothing the mass out on a smooth surface
with a spatula
• Trituration
– is the process for reducing the particle size of a substance
by grinding, eg grinding of powders in a mortar with a
pestle
• Sifting
– relates to putting through a sieve or straining device to
separate fine particles from coarse ones
• Tumbling
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18. Advantage of powders/granules
1. Stability
– Solid are more stable than liquids
– E.g. (Ampicillin)
• Antibiotics powders dry form = 2-3 yrs shelf life
• While liquid of same antibiotics = 1-2 weeks
2. More suitable/convenient DF for large dose
– E.g. Mag.Trisillicate Antacid (1-5g)
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19. 3. Faster dissolution rate/Bioavailability
– Increase S.A ------- increase dissolution
– Rapid onset of action
4. Can be taken orally by some patients who are
unable to swallow other solid dosage forms
such as capsules and tablets
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20. Disadvantages
• Inconvenient to carry / handle
– (except when presented as divided DF)
• Unpleasant Taste
• Not very suitable DDS for potent drugs
– Divided DF can be used however Tabs are preferred
• Not suitable for acid labile / Enzyme prone drugs
(Coated granules may be used)
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21. Disadvantages……. (Cont.)
• Poor/Misunderstanding about correct method of
use
• Higher decomposition rate incase of
– Hygroscopic, deliquescent or aromatic ingredients
• Because of different particle size/density diff.
powder mix can be partly separated. Non
uniform distribution
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22. Powders VS Granules
Powders Granules
• Comparatively poor flow properties • Flow well compared to tablets, good
choice for compressing tabs
• Relatively less stable (physically and
Chemically) due to inc. S.A & Atm.
Effect
• Has less surface area, more stable to
atm. effect
• More likely to hardening / cake
formation on long storage
• Less likely
• For some powders, drugs float on the
surface, difficult to make solution
• More easily wetted by the solvents,
good choice reconstitution liquids
• Relatively poor compressibility • Good compressibility
• Chances of non uniform dosing are
more
• Relatively more uniformity of contents
in case of granules
• More dust due to small p.s • Generate less dust on handling
• Comparatively less appealing • Have a more elegant appearance
• Relatively simple method of
processing/formulation
• It involves more processing, exposure
to heat and contact with solvents
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23. Preparation of Granules
• Wet method
– Moistening the desired powder
– Passing paste like mass thru sieve no 4-14.
– Tray dry / oven dry / vacuum dry
– Packed and labeled
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24. • Dry method
– Powder material is passed through a roll compactor
– Granulating machine.
– Densified sheets or flakes
– The compacted powder is then granulated to uniform
particle size by passing through a mechanical
granulator.
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26. Powders and granules as
dosage form.
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27. Powders /
Granules
Therapeutic use:
As a true & proper
pharmaceutical
dosage form
Non therapeutic use:
for the preparation of
other dosage forms
Tablets,
Capsules,
Suspensions,
Solutions etc
Bulk/divided/d
usting/insufflati
ons/DPI/Reco
nstitution
All powders are stored
at dry place
Away from children
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28. Bulk Powders
• Mixed ingredients are packed suitable
containers like wide mouthed bottles or glass
jars
– Constituents are non toxic / Less potent
– Large doses can be dispensed
– Usually supplied with a measuring spoon
– Proper directions for use should be provided
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29. Bulk Powders (Cont…)
• E.g.
– Compound Mag Trisilicate powder
– Refreshens salt (laxative)
– Douch powders for vaginal irrigation/ cleansing
– Dietry suppliments and feeding formula.
• STORAGE: wide mouthed bottles, plastic / glass,
Cool and dry place, out of children reach
• Prepare a list of at least 3 bulk powders
available in Botswana,
– Ingredients, Uses, type of packaging etc.
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30. Bulk Powders (Cont…)
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31. Divided powders
• More potent ingredients are usually packed
individually/ separately wrapped.
– List advantages / Disadvantages
• E.g.
– Mag. Trisilicate powder individually wrapped
– Grand Pa , (?)
– Acetyl cystine
– List some more with ingredients (check Community
Pharmacy)
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32. Divided powders (Cont…)
• Packaging
– Ind. Wrapped paper, (How to wrap)
– If material is volatile or moisture sensitive than wax
lined paper or grease proof paper
– Air tight sealed sachets
– Foiled laminate (replaced Paper)
– Individual powder are than boxed. (easy handling)
• Storage
– Cool and dry place, Avoid moisture (avoids
agglomerates formation)
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33. Divided powders (Cont…)
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34. Dusting Powders.
• Used externally for
– Therapeutic ---- antifungal
– Prophylaxis----- antifungal/antiseptic
– Lubricating------ talc, Kaolin etc
• Dusting powders for open wounds should be
sterile (chlorohexidine Dusting Powders), but lubricating
powders do not need to be sterilized, however
should be free from pathogens/Spores,
• Dry heat for sterilization is usually used,, (1600C for
more than 60 minute)
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35. Dusting Powders.(Cont…)
• Packaging,
– Plastic, Glass or metal drum fitted with a perforated lid.
– Glidents are usually added to enhance the flow (Talc,
Sterillizable Maiz starch)
• Storage:
– Closed Lid, Dry place, Away from child…..
• Examples
– Antifungal/ Antibacterial foot powders.
• Zinc undecylinate, Chlorohexidine
– Lubricating dusting powder,
• Talc
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37. Insufflations
– Are medicated powders intended to be blown into regions
such as ear, nose, and throat with the help of an
insufflators
• Not very acceptable, In-elegent and less convenient to
use,
• May show systemic effects (Rapid abosrption)
– Some drugs are more rapidly absorbed from lungs than
oral use. E.g. Sodium Chromoglycolate
– Traditional insufflator replaced by Advance devices,
• Handihaler,
• Accuhaler, Etc.
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38. Dry powders for inhalation (DPIs)
– DPIs are used to deliver medicaments to lungs in a
dry powder form using a hand-held device, as you
inhale through it.
– It does not have propellant like MDI do.
– E.G
• Seretide Accuhaler,
– (Can you list what does serretide contains)
• Handihaler
– Uses a capsule in device which is broken down as you
operate and than u inhale medicaments.
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41. FDA approved Afrezza (Insulin DPI)
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42. Video Demonstration
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43. • For optimum delivery and absorption into the
lungs,,,,,,,, What should be the Particle size
????
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If particle size is less than 0.5 micron, than drug may be exhaled
out with breath when given as powdered DF…...

45. Oral antibiotics powders
• Reconstituted at the time of use.
• Moisture can cause degradation of the product,
So presented as dry powder for reconstitution
– E.g.
• Phenoxy methyl peicillin.
• Cefaclor,
• Augmentin
• List more
– Shake well before use for suspension
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46. Powder for injections (PFI)
• Sterile powders in ampoule / Vials
– Must be made immediately before use
– Diluents WFI
– Contains other additives along with active moiety
• E.g.
– Augmenting PFI
– Amphoteracin B, Ampicillin, Ceftriaxone PFI
– Cephradine, and chloramphenical PFI
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47. Special problems in
Powdered DF / Solution
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48. Volatile substances
• Such as
– Camphor, menthol, essential oils
– Evaporation loss.
• Solution
– Packed into heat sealed plastic bags,
– Air tight containers
– Proper storage instructions to the client
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49. Eutectic mixture
• Some solids when mixed together form liquid.
– E.e. Phenol, menthol, thymol, antipyrene,
phenacetin.
• Solution.
• Adding inert diluents such as
• Mag. Carbonate
• Light Mag oxide
• Kaoline,
• Starch,
• Bentonite
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50. Liquids
• Can be added in small amounts to powders.
– Some adsorbing materials should be added.
– Lactose,
– Mag.Carbonate, Starch.
• Fluid extract & Tinctures used in this way
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51. Hygroscopic or Deliquescent material
• Absorb moisture from air and liquefy
– Increase rate of hydrolysis
• Packed in air tight containers.
• Inert diluents can be added.
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52. Efflorescent materials
• Crystalline substances may liberate water of
crystallization due to trituration and powder
becomes wet.
– Anhydrous salt form can be used.
– Inert diluents can be added.
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53. Factors affecting Drug
availability from
Powdered DF
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54. Some basic concepts
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57. • Particle size can influence a number a factors
– Dissolution rate
– Suspendability
– Uniform distribution
– Penetrability
– Texture of the formulation
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58. Dissolution
• Process by which a drug particle dissolves
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Noyes Whiteny
Equation

59. Surface area
• Particle size is inversely related to S.A
• Poorly or slowly soluble drugs when presented
in small particle size…… enhanced
dissolution…… enhanced bioavailability
• E.g.
– Theophyllin,
– Griseofulvin
• Micronized powder in SDF show more rapid
absorption
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60. Crystal or amorphous form
• Amorphous form of a chemical is more soluble
than its crystalline counterpart.
– E.g.
• Chloramphenicol is ineffective in its crystalline form
but show good absorption through GIT in its
amorphous state
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61. Salt form
• Drugs are either week acid or week basis.
– E.g.
• EthyleneDiAmine salt of Theophyyline has 5-Fold water
solubility
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Sodium and potassium salts of week organic acids
&
Hydrochloric salts of week organic basis
SHOW
Rapid dissolution rate than respective free
drugs

62. Sate of hydration
• Anhydrous form of an organic molecule is more
soluble than its hydrated counter part.
• E.g.
– Ampicillin Anhydrous is more soluble than its tri-
hydrate form
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63. Effect of pH
• Unionized form of drug absorb more faster than
ionized form.
• Week acidic drugs absorb well in acidic pH. i.e
Stomach
• Basic drugs absorb well in intestine.
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64. Particle size and Size
distribution analysis
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65. Particle size and Size distribution analysis
• A number of methods can be used including
1. Microscopy
• Calibrated grid background
2. Sieving
3. Sedimentation rate
• Terminal settling velocity
4. Light energy diffraction
• Reduction of light reaching the sensor
5. Laser holography
• 3D picture by holography camera
6. Cascade impact
• Striking surface with air stream
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66. Sieving technique
• Sieve number ?
• Sieve Opening ?
• Principle
– Particles passed by mechanical shaking through a
series of sieves of known sizes (which reduces
gradually from top to bottom),
– Amount of powder retained / Passed through is
determined and manipulated
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67. • Sieves are usually made up of wired cloth woven
from
– Brass,
– Bronze or other metals
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Sieve No. Sieve Opening
(µm)
20 850
40 425
60 250
80 180
120 125
….. ….
400 38

68. • USP characterize Powders by following
descriptive terms
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Type of powder All particles pass
thru Sieve No
Not more than
Very coarse 8 20% thru 60
Coarse 20 40% thru 60
Moderately coarse 40 40%thru 80
Fine 60 40% thru 100
Very fine 100 No limit

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70. Powders calculations
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71. • While dealing powders calculations
– Always calculate for at least 1 extra powder to
compensate loss of powder during manipulations
– If amount of active ingredient is less than minimum
weighable qty than dilutions (triturations) are to be
made
– Min. weighable qty is diluted over several time to
obtain req. dose
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72. A. Doubling up method / Trituration
B. Calculations involving powder volumes
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73. • E.g.
Rx
Hyoscine HBr 300 mcg
mitte 4 powders
one to given 30minutes before journey
(Remember: minimum powder weight for divided powder = 120mg)
Calculate for 5 doses
Active req. = ?
Diluent (lactose) req. = ?
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74. • Step-1
– Hyoscine HBr =100mg
– Diluent =900mg
• Step-2
– Triturate A =100mg
– Diluent =900mg
• Step-3
– Triturate B =?
– Diluent =?
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75. • Example
Rx Send 10 aspirin powders 200mg for a child
of 3-years (14kg)
– Is dilution required?
– 300 mg tabs are available in dispensary
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76. • Example
– Calculate quantities required to make 8 powders each
containing 200mcg of digoxin per 120 mg of powder.
• Use lactose as a diluents
• Min. weighable qty = 100mg (class B balance)
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77. Calculation involving powders volume
• Powder displacement
• Example
a) Calculate the volume of suspension occupied by
amoxicillin powder
• 150mL – 111mL = 39mL
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78. b) Quantity of amoxicillin present in entire bottle
• 5mL contains =250mg
• 150mL contains =7500mg
c) Volume of suspension that will contains
500mg/5mL
• 7500mg /500mg/5mL =75mL
d) Volume of purified water required
• 75mL-39mL =36mL of water to be added.
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79. • If the volume of 250mg of ceftriaxone sodium
(powdered) is 0.1mL. How many mL of diluents
should be added to 500mg of ceftriaxone to
make 250mg / mL concentrated suspension.
– Volume of ceftriaxone ?
– Final volume of product.?
– Volume to be added.?
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81. Some practice problems
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