1. Powders
A pharmaceutical powder is a mixture of finely divided drugs and/or chemicals in dry form meant for internal or external use. This should differentiated from general use of term powder or powdered which is commonly used to describe the physical state of a single chemical substance or single drug.

4. A powder may be finely subdivided preparation, coarsely comminuted product or product of intermediate particle size. It may be prepared from a naturally occurring dried vegetable drug or it may be a physical admixture of two or more powdered pure chemical agents..

5. Powders may contain small proportion of liquid dispersed thoroughly and uniformly over the solid components of the mixture or powder may be composed entirely of the solid materials.

6. According to BP the particle size range is 1.2 – 1.7 mm.
Excipients may be added as coloring, flavoring or sweetening agents.
Powders may contain small proportion of liquid dispersed uniformly over the solid particles.
Granules which are used as a dosage form consist of powder particles aggregated to form large particles of size range 2 – 4 mm.

7. Advantages of powders
Flexibility of compounding
2- More stable than liquid preparation ( good chemical stability)
3- Convenient to dispense drugs with large doses such as compound magnesium trisilicate oral powder.

8. 4- Rapid dispersion of ingredients because of the small particle size.
5- Orally administered powders and granules of soluble drugs have a faster dissolution rate and absorption than tablets and capsules.

9. Disadvantages of powders
Time consuming in preparation especially in divided doses
Dose inaccuracy
Unsuitability for many unpleasant tasting drugs

10. 4- They are not suitable dosage form for potent drugs
5- Powders and granules are not suitable dosage forms for drugs which are inactivated in the stomach
6- Powders containing hygroscopic or aromatic ingredients cannot be protected

11. Fundamental properties of powders
Particle size and size distribution
The size of a shape is readily expressed in terms of its diameter. As the degree of asymmetry of particles increases, the difficulty of expressing size in terms of diameter increases.

12. Under these conditions, there is no one diameter for a particle
Under these conditions, there is no one diameter for a particle. Therefore, we use equivalent spherical diameter which relates the size of the particle to the diameter of sphere having the same surface area (ds), volume (dv) or sedimentation rate (dst).
Surface diameter: (ds) It is the diameter of sphere having the same surface area as the particle in question.

13. Volume diameter: (dv) The diameter of a sphere having the same volume as the particle in question.
Stoke's diameter: (dst) It describes the diameter of sphere having the same sedimentation rate as the particle in question.

14. Surface area of spherical particle = π d2
Surface area of asymmetric particle= π d2s
Where ds is the equivalent surface diameter.
Volume of spherical particle = π d3/6
volume of asymmetric particle = π dv3/6 where dv is equivalent volume diameter

15. Specific surface: it is the surface area per unit volume ( Sv ) or per unit weight (Sw )
Sv = surface area of the particle / volume of the particle
Sw = surface area of the particle / weight of the particle

16. Importance of controlling particle size in pharmacy
The particle size and the surface area of a drug can affect its physical, chemical, and pharmacological properties.
The particle size of a drug can also affect its release rate from dosage form.

17. 3- Successful formulation of suspensions depends on the particle size of the drug.
4- In tablet and capsule manufacture, control of the particle size is essential for the flow properties and proper mixing of granules and powders.

18. Particle size distribution
Any collection of particles is usually heterogeneous, i.e. particles of more than one size are present.
The size ranges present in a sample, and the number or weight of particles in each size range is called the particle size distribution, which can be represented by two curves, the frequency distribution curve and cumulative frequency distribution curve.

19. 3- Presentation of the data:A- Table form
Cumulative %
% of particles
No. of particles
Mean (µm)
Size range (µm)
6.5
6.5% 96
2.5
0-5
13.6 ( )
7.1%
105
7.5
5-10
21.4 ( )
7.8%
116
12.5
10-15
30.2%
8.7%
129
17.5
15-20
150
22.5
20-25
212
27.5
25-30
148
32.5
30-35
127
37.5
35-40
114
42.5
40-45
6.8%
101
47.5
45-50 92
52.5
50-55
99.4%
5.6% 88
57.5
55-66
Total = 1478
∑ ni
The cumulative % over size is interpreted as the percent of the number of particles that are more than the stated size.
e.g. in the table, 99.4% all the particles are more than 57.5 µm.

20. Frequency -distribution curve

21. Frequency- distribution curve
Asymetric distribution curve Symetric distribution curve Normal distribution curve Skewed-distribution curve

22. Cumulative -distribution curve

23. 2-Particle shape and surface area
The shape of the particle has an important influence on certain properties such as:
A-Flowability: spherical particles are more flowable than irregular ones
B-Packing properties: irregular particles may be able to pack together more closely than spherical particles giving a higher bulk density.

24. C-Surface area: spherical particles have minimum surface area per unit volume.
D-Rheological properties:
Pharmaceutical suspensions are also affected by the shape of the particles that they contain.
The surface area of the particles affect both their physical (dissolution rate and adsorption) and chemical properties
( reaction rate and stability).

25. Methods of determining particle size
1- Microscopy
The ordinary optical microscope is used for particle size measurement in the range of 0.5 – 100µ, while the electron microscope is applicable for sizes ranging from – 1.0µ.

26. A sample of the powder is suspended in a suitable diluents, mounted on a slide and placed on a mechanical stage. The eyepiece is fitted with a micrometer by which the size of the particle can be estimated.

27. Disadvantages of microscopic method
The diameter is obtained from only two dimensions of the particle, length and width. No estimation of the depth ( thickness) of the particle can be made.
A large number of the particles must be measured (300 – 500) in order to obtain a good estimation and this renders the method slow.

28. Sieving
Powders with particle size range of 50 – 500 µ can be measured by sieving method. This method utilizes a series of standard sieves with different mesh sizes.
The sieves are arranged in a nest of about five sieves with coarsest at the top.

30. A carefully weighed sample of the powder is placed on the top sieve and the sieves are shaken for a certain period of time by the use of mechanical shaker.
The fraction of powder retained on each sieve is weighed and a plot of weight against size is made to obtain the frequency distribution curve.
Sieving errors can arise from:

31. Sieving errors can arise from: Overloading of the sieve
Forcing the powder through the sieve by spatula
Insufficient time of agitation
Inadequate intensity of agitation

32. 3-Sedimentation
The size of particles suspended in a liquid may be determined by measuring the rate at which the particles settle down in a graduated cylinder and applying
Stock's law which states that:
V = h/t = dst2 (p – po) g / 18η

33. Where:
V = rate of settling.
h= distance of fall in time t
dst = mean particle diameter based on rate of settling ( stock's diameter)
p = density of the particle
Po = density of the dispersion medium
G = acceleration due to gravity
η=viscosity of the dispersion medium

34. the diameter obtained by the sedimentation method is the diameter of sphere having same sedimentation rate as the particle under test (Stock's diameter).
Sedimentation method is used for particle size range of µ
For accurate results, two precautions should be considered:

35. Dilute suspension should be used ( less than 2%) to allow free settling of the particles without hindrance.
A suitable deflocculating agent must be added to keep the particles separate without aggregation.
Several method based on sedimentation are used, the most important are the pipette method and the balance method.

36. The pipette method
An apparatus called Andreasen apparatus is used. It consists of 500ml vessel containing a 10 ml pipette which is lower end is 20 cm below the 500 ml mark of the vessel.

37. 500ml of 1% suspension of the powder in the medium containing suitable deflocculating agent is introduced into the vessel which is then shaken to distribute the particles uniformly throughout the suspension.

38. At various time intervals, 10 ml samples are withdrawn and weight of powder present in each sample is determined either by evaporating the liquid and weighing the residue, or by any other suitable assay method.
The particle diameter corresponding to the various time intervals is calculated from Stock's law, with h = 20 cm

39. The balance method
The powder suspension is introduced into a vessel containing a balance pan at its bottom. The weight of particles that settle on the balance pan continuously recorded at various time intervals, and the particle diameter corresponding to each weight is calculated from stock's law, where h= height of suspension above the balance pan.

41. Particle volume measurement
An instrument that measure the volume of particles called coulter counter
This instrument operates on the principle that when a particle suspended in a conducting liquid passes through a small orifice, on either side of which are electrodes, a change in electric resistance between the electrodes occurs.

43. A constant voltage is applied across the two electrodes to produce a current
A dilute suspension of the particles is made up in a suitable electrolyte solution e.g. sodium chloride, and then pumped through the orifice.

44. Provided the suspension is sufficiently dilute, the particles pass through the orifice one at a time
As the particles travels through the orifice, it displace its own volume of electrolyte resulting in an increase resistance between the two electrodes

45. Such change in resistance produce voltage pulses which are proportional to the particle volume and can be amplified, measured and counted.
The particle volume can be converted to particle diameter from the relation:
Volume of spherical particle = π d3/6
Volume of asymmetric particle = π dv3/6
Coulter counter can be used for measuring particle size in the range µ

47. Advantages:
This equipment can count large number of particles (500/min) very rapidly.
Yield highly reproducible results.
Because of the large number of particles, statistics will be easy and yield high level of confidence in the distribution of a sample.

48. Disadvantages:
Cost of equipment.
The possibility of orifice blockage by the particles.
The electrolyte used must be specific and in which the material to be counted is insoluble.
Wrong results are produced if there is electrolytic back ground.

49. Powder’s chracters which measured: 1-Porosity
Suppose a powder is placed in a graduated cylinder, the volume occupied by the powder is known as the bulk volume (Vb).
The bulk volume of the powder consists of the true volume of the solid particles (Vp) plus the volume of the spaces between the particles which is known as the void volume (V)

50. Thus V = Vb - Vp
Thus the porosity or voids ( Ɛ ) of the powder is defined as " the ratio of the void volume to the bulk volume".
Thus Ɛ = V b - Vp / Vb
The porosity is frequently expressed in percent, Ɛ × 100

51. 2- Density
Density is defined as the weight per unit volume.
There are three types of densities:
1-True density: it is the density of the actual solid material.
2-Granule density: it is the density of the material with its intra – particle pores.
3- Bulk density: it is the density of the material with its intra – particle pores and voids spaces.

52. 3-Cohesion
Cohesion is defined as the stress necessary to shear a bed of the powder under conditions of zero normal load.
Factors influencing cohesion:
1-Particle size: fine particles are more cohesive than coarser ones. Below 10µ, most powders are extremely cohesive.

53. Particle density: light particles are more cohesive than heavy ones.
Particle shape: spherical particles are less cohesive than irregular ones.

54. Humidity: a low % of the adsorbed moisture on the surface of the particles will reduce the surface energy of the particles and decrease cohesion of the powder. However, a continuous film of moisture surrounding the particles can cause a great increase in cohesion.

55. 4- Flowability
The ability of a powder to flow is one of the factors involved in mixing of different materials to form a powder blend.
The friction forces in a powder can be measured by angle of repose (ɸ).

56. The angle of repose (ɸ):
If the powder is poured freely onto a plane surface, it forms a cone that has a constant angle between the surface of the pile and the horizontal plane. This angle is known as the angle of repose, and for most pharmaceutical powders, it ranges from 34 to 48º.
ɸ =h/r
Where h= height, r= radius

58. The angle of repose depends on the mutual friction between the particles. With an increase in friction, the resistance to flown is increased with subsequent increase in the angle of repose. The angle of repose permits evaluation of the granulation before compression is attempted.

59. To improve the flow properties, materials termed glidants are frequently added to granular powders. Examples of commonly used glidants are magnesium stearate, starch and talc.

60. Reduction of particle size
Substances to be incorporated in a powder are frequently milled to reduce particle size. After milling the various substance are mixed as needed.
Milling is the mechanical process for reducing the particle size of solids before incorporation into final products.

61. Advantages of milling
1- increases surface area which may increase dissolution rate and bioavailability
2- facilitate drying of wet masses by increasing surface area
3- improves mixing or blending of several solid ingredients if they are reduced, to the same particle size to minimize segregation and provides greater dose uniformity

62. 4- permits uniform distribution of coloring agents in artificial colored solid pharmaceuticals
5- improves the function of lubricants used in compressed tablets and capsules to coat the surface of granules or powders
6- improves the texture, appearance, and physical stability of ointment, creams and pastes

63. Disadvantages of milling
1- may change the polymorphic form of the active ingredients, rendering it less active, inactive or unstable.
2- may cause degradation of drugs as a result of heat during milling, oxidation or adsorption of unwanted moisture due to increased surface area.

64. 3-decreasing particle size may create static charge problems that may cause particle aggregation and decreasing dissolution rate.
4- increasing surface area may promote air adsorption that may inhibit wetability of the drug

65. Methods of particle size reduction
On large scale, various mills are used e.g. the rotary cutter, the hammer, and the roller mills
On small scale the following techniques may be used:
1- trituration
The substance is reduced to small particles by rubbing it in a mortar with pestle

66. 2- pulverization:
The substance is reduced and subdivided with an additional material that can be removed easily after pulverization is complete.
As camphor which is pulverized with alcohol or iodine with ether

67. Levigation
The substance is reduced in particle size by adding a suitable non- solvent (levigating agent) to form a paste in a mortar and pastle.
The method is used to incorporate solids into dermatologic or ophthalmic ointments and suspensions to prevent a gritty feel. Mineral oils is a common levigating agent

68. Hammer mill

69. Fluid energy mill

70. Vibration mill

71. Mixing of powders
1-Spatulation:
Small amount of powders are blended by movement of spatula through the powder on a sheet of paper.
The method is not suitable for large quantities of powder containing one or more potent drugs because homogeneous blending may not occur.

72. It is particularly useful for solid substances that liquefy or form eutectic mixtures ( mixture that melts at lower temperature than any of their ingredients ) when in close and prolonged contact with one another, since little compression or compaction results.

73. It is used to comminute and to mix powders.
2-Trituration:
It is used to comminute and to mix powders.
If comminution is desired, a porcelain mortar with rough inner surface is preferred than glass mortar with smooth working surface.
A glass mortar may be preferred for chemicals that may stain the porcelain mortar and for simple mixture of substances without need of comminution. 2-

74. 3-Geometric dilution
It is employed when a potent drug is to be mixed with large amount of diluents.
The potent drug is thoroughly mixed by trituration with an approximately equal weight of the diluents in a mortar

75. 3-A second portion of diluents equal weight to the powder mixture in the mortar, is added and trituration is repeated.
4-The process is continued, adding diluents equal in weight to mixture in the mortar at each step until all the diluents incorporated.

76. 4-Sifting
During sifting, powders are mixed by passing them through sifters
The process results in a light, fluffy product and is generally not acceptable for incorporation of potent drugs into a diluents base.

77. 5-Tumbling
It is a process of mixing powders in large container rotated on its axis by a motor
These blends are widely used in industry.

78. 1-Tumbling mixers

79. Powders as a dosage forms  
A-Bulk powders
They are dispensed by the pharmacist in bulk containers; a perforated or sifter can for external dusting, an aerosol container for spraying onto the skin, or a wide mouthed glass container that permits the entrance of the spoon and easy removal of a spoonful of powder. Powders are classified as:

80. 1-Oral powders
The finely divided powders are intended to be suspended or dissolved in water or other liquid. Antacid and laxative powders are frequently administered in this form.

81. 2-Douche powders
They are generally dissolved in warm water by the patient for vaginal use, although they may be formulated for nasal, otic or ophthalmic use.
3-Dentifrice or dental cleansing powders
Used in dental hygiene

82. 4-Denture powder
Some are used as dentifrice powders and others as adhesives to hold the dentures in place.
5-Triturations
They are dilution of potent powdered drugs, prepared by mixing them with a suitable diluents in a definite proportions by weight. They were official as 1 – 10 dilutions.

83. 6-Insufflations
They are finely divided powders introduced into body cavities as the ears, nose, throat, tooth sockets and vagina by the aid of insufflators ( powder blower).
Pressurized aerosols also have been used as a means of administering insufflations especially for the potent drugs.

84. 7-Dusting powders
They are locally applied non- toxic preparations that are intended to have no systemic actions
They should be dispensed in a very fine state of subdivision to enhance effectiveness and minimize irritation.

85. They are applied to different parts of body as lubricants, protective, adsorbents, antiseptics, antipruritus, astringents and antiperspirants.
Although in most cases dusting powders are considered non- toxic, the absorption of boric acid through large areas of abraded skin has caused toxic reactions in infants. Accidental inhalation of zinc stearate powder has led to pulmonary inflammation of the lungs of the infants.

86. B-Divided powders
They are dispensed in the form of individual dosed, generally in properly folded papers.
However, they may also be dispensed in metal foil, small heat sealed plastic bags or other containers.
After weighing, comminution and mixing of the ingredients, the powder is divided into prescribed number doses.

87. Special problems
Volatile substances as camphor, menthol or essential oils may be lost by volatilization after incorporation into powder. This problem is prevented or retarded by using heat sealed plastic or foil packets or by double wrapping with waxed paper.

88. Liquids may be incorporated into divided powders in small amounts
Liquids may be incorporated into divided powders in small amounts. Magnesium carbonate, starch or lactose may be added to increase the adsorbability of the powder by increasing the surface area.
When a liquid is a solvent for non – volatile, heat stable compound, it may be evaporated gently on water bath. Some fluid extracts and tinctures may be treated in this way.

89. Hygroscopic substances that become moist because of their affinity to moisture in air may be prepared in divided powders by adding inert diluents. double wrapping or foil packets provide further protection.

90. Eutectic mixture: in order to diminish contact, powder prepared from such substances is commonly mixed in the presence of an inert diluents such as light magnesium oxide or carbonate to separate the trouble some agents.

91. Official powdered vegetable drugs
They are utilized in the preparation of corresponding dosage forms:
Powdered belladonna extract
Powdered Ipecac
Powdered opium
Powdered digitalis
Powdered cellulose is utilized as pharmaceutical aid as a tablet diluents, adsorbent, and suspending agent.

92. Official powders (USP)
Absorbable dusting powders: used as surgeon's gloves lubricant.
Methylbenzethonium chloride powder: local anti-infective powder used for diaper rash in infants.

93. Tolnaftate powder and aerosol: used in treatment of fungal infection.
Compound iodochlorohydroxyquin powder: used as vaginal insufflations as antifungal.
Nystatin topical powder: as topical dusting powder in treatment of mycotic infections.
Tolnaftate powder and aerosol: used in treatment of fungal infection.