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Powder Particle Size Determination Methods for tablets

Particle Size Determination Methods:
1. Sieving
2. Microscopy
3. Sedimentation rate method
4. Light energy diffraction
5. Laser holography
6. Cascade impaction

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

2. 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.

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

4. Cascade impaction:
• The principle 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 airstream.

5. 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.

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

• Particle size is characterized using these terms:
− Very coarse (#8)
− Coarse (#20)
− Moderately coarse (#40)
− Fine (#60)
− Very fine (#80)

Powder Flow Properties:
Flowability of powder and chemical stability depends on the habit and internal structure of a 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 change in particle size, shape and density.

• The flow properties depend upon following-
(i) Force of friction.
(ii) 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:
• By determining Angle of Repose.
• A greater angle of repose indicates poor flow.
• It should be less than 30° and can be determined by following equation:
tan θ = h / r
where, θ = angle of repose.
h = height of pile.
r = radius.


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

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

Surface Area:
• Particle size and surface area are inversely related to each other.
• Smaller the drug particle, 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 following cases when drug is unstable.
• Degrade in solution form.
• Produce undesirable effects.
• When sustained effect is desired.

Solubility Analysis:
• Preformulation solubility studies focus on drug solvent system that could occur during the delivery of drug candidate.
• 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.

For determination of solubility the following points should be considered:
• The solvent & solute must be pure.
• 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.
• The method of analyzing solution must be reliable
• Temperature must be adequately controlled.
• General Method of Increasing
• the Solubility

• Addition of co-solvent
• pH change method
• Reduction of particle size
• Temperature change method
• Addition of Surfactant
• Complexation
• 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 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 solubilising phenolic compounds for use as disinfectants-Lysol, Roxenol etc.
• Barbiturates, anticoagulant, alkloidal 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 the pharmacists:
(i) Chemical: Each active ingredient retains its chemical integrity within the specified limits.
(ii) Physical: The original physical properties (including appearance, taste, color and odor) are retained.
(iii) Biological: Sterility is retained (No microbial growth).


About Pharmaceutical Guidanace

Mr. Shiv Kumar is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 14 years of rich experience in pharmaceutical field. During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube

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