Particle Size Determination Methods for Tablets Powder

Particle Size Determination Methods:

1. Sieving
2. Microscopy
3. Sedimentation rate method
4. Light energy diffraction
5. Laser holography
6. Cascade impaction

Sieving Method

• Range: 50 – 150 μm
• Simple, inexpensive
• If the powder is not dry, the apertures get clogged.

Microscopy

• Range: 0.2 – 100 μm
• Particle size can be determined by the use of calibrated grid background.
• Most direct method.
• Slow and tedious method.

Sedimentation Method

• Range: 1 – 200 μm
• Andreasen pipette is used.

Light Energy Diffraction

• Range: 0.5 – 500 μm
• Particle size is determined by the reduction in light reaching the sensor as the particle, dispersed in a liquid or gas, passes through the sensing zone.
• Quick and fast.

Laser Holography

• Range: 1.4 – 100 μm
• A pulsed laser is fired through an aerosolized particle spray & photographed in three dimensional with a holographic camera, allowing the particles to be individually imaged & sized.

Cascade Impaction

• The principle is that a particle driven by an airstream will hit a surface in its path, provided that its inertia is sufficient to overcome the drug force that tends to keep in it in an airstream.

Particle size is characterized using these terms:

1. Very coarse (#8)
2. Coarse (#20)
3. Moderately coarse (#40)
4. Fine (#60)
5. Very fine (#80)

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Powder Flow Properties:

• The flowability of powder and chemical stability depends on the habit and internal structure of the drug.
• Habit is the description of the outer appearance of a crystal. A single internal structure for a compound can have several different habits, depending on the environment for growing crystals. Different habits of crystals are given below.
• Powder flow properties can be affected by changes in particle size, shape, and density.
• The flow properties depend upon the following-

1. The force of friction.
2. Cohesion between one particle to another.

• Fine particle possesses poor flow by filling void spaces between larger particles causing packing & densification of particles.
• By using glidant we can alter the flow properties. e.g. Starch, Talc.

Determination of Powder Flow Properties:

1.  By determining the Angle of Repose.

• A greater angle of repose indicates poor flow.
• It should be less than 30° and can be determined by the following equation:

tan θ = h / r

Where, 

θ = angle of repose.

h = height of pile.

r = radius.

2.  Measurement of free-flowing powder by compressibility:

• Also known as Carr’s index.

Car’s index (%) = (Tapped density − Poured density) / Tapped density × 100

Tapped Density:

It is a simple, fast, and popular method of predicting powder flow characteristics.

3.  Particle Shape:

• Particle shape will influence the surface area, flow of particles, and packing & compaction properties of the particles.
• A sphere has a minimum surface area per unit volume.
• Therefore, these properties can be compared for spheres & asymmetric particles, to decide the shape.

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4.  Surface Area:

• Particle size and surface area are inversely related to each other.
• Smaller the drug particle, the greater the surface area.
• Specific surface is defined as the surface area per unit weight (Sw) or unit volume (Sv) of the material.
• However, size reduction is not required in the following cases when the drug is unstable.
• Degrade in solution form.
• Produce undesirable effects.
• When the sustained effect is desired.

Solubility Analysis:

• Pre-formulation solubility studies focus on drug solvent systems that could occur during the delivery of drug candidates.
• e.g. A drug for oral administration should be examined for solubility in media having isotonic chloride ion concentration and acidic pH.
• Analytic methods that are particularly useful for solubility measurement include HPLC, UV Spectroscopy, Fluorescence spectroscopy, and Gas chromatography.
• Reverse phase HPLC offer accurate and efficient means of collecting solubility data of drug.

Partition Coefficient

• It is the ratio of the unionized drug distributed between the organic and aqueous phases at equilibrium.

• For the determination of solubility, the following points should be considered:

1. The solvent & solute must be pure.
2. A saturated solution must be obtained before any solution is removed for analysis.

• The method of separating a sample of saturated solution from undissolved solute must be satisfactory.

1. The method of analyzing the solution must be reliable
2. The temperature must be adequately controlled.

General Method of Increasing the Solubility

1. Addition of co-solvent
2. pH change method
3. Reduction of particle size
4. Temperature change method
5. Addition of Surfactant
6. Complexation
7. Applications of solubilization

• Drugs with limited aqueous solubility can be solubilized. These include oil-soluble vitamins, steroid hormones, and antimicrobial agents, etc.
• Both oil-soluble and water-soluble compounds can be combined in a single-phase system as in the case of multivitamin preparations.
• Solubilization may lead to enhanced absorption and increased biological activity.
• Drug absorption from ointment bases and suppositories also increased.
• Aqueous concentrates of volatile oils can be prepared by solubilization.
• Example: soaps used for solubilizing phenolic compounds for use as disinfectants-Lysol, Roxenol, etc.
• Barbiturates, anticoagulants, alkaloidal drugs are dissolved with polysorbate by solubilization.

Formulation Challenges with Poorly Soluble Compounds:

• Poor dissolution rate
• Low and variable bioavailability
• More potential for food effect
• Inability to deliver high doses for toxicity studies
• Difficulty in developing parenteral formulations Stability:
• Stability is the extent to which a product retains (throughout its period of storage and use, i.e., its shelf life) the same properties that it possessed at the time of its manufacture.
• One of the principles of dosage form design is to ensure that the chemical integrity of drug substances is maintained during the usable life of the product.
• Three types of stability concern pharmacists:

1. Chemical: Each active ingredient retains its chemical integrity within the specified limits.
2. Physical: The original physical properties (including appearance, taste, color and odor)are retained.
3. Biological: Sterility is retained (No microbial growth).

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