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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.
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..
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.
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.
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.
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.
Disadvantages of powders • Time consuming in preparation especially in divided doses • Dose inaccuracy • Unsuitability for many unpleasant tasting drugs
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
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.
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.
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.
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 dvis equivalent volume diameter
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
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.
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.
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.
3- Presentation of the data:A- Table form 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.
Frequency- distribution curve Asymetric distribution curveSymetric distribution curve Normal distribution curve Skewed-distribution curve
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.
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).
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 0.005 – 1.0µ.
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.
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.
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.
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:
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
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
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
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 0.5 - 100µ • For accurate results, two precautions should be considered:
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.
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.
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.
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
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.
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.
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.
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
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 1- 100µ
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.
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.
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)
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
