Powders - Dosage Form

POWDERS

Definition

• Powders are the simplest dosage forms and the basis for tablets, capsules, etc.
• Originally designed for administering hard vegetable drugs (roots, barks, woods).
• Particle size ranges from 0.1 to 10 microns.
• USP Definition:
  • "Intimate mixtures of dry, finely divided drugs and/or chemicals intended for internal (Oral Powders) or external (Topical Powders) use."
  • A solid, or mixture of solids reduced to a finely divided state.
• Varying sizes between $10nm$ and $1000µm$.

Classification of Powders

• Details on the classification will be provided later.

Advantages of Powders

• Easy to alter medication quantity for each dose.
• Good chemical stability compared to fluids.
• Useful for bulky drugs with large doses (e.g., indigestion powder).
• Easy to swallow, even in large bulk, especially when mixed with food or drink (useful for stomach-tube feeding).
• Smaller particle size allows for rapid dissolution in body fluids.
• Increased drug bioavailability.
• Decreased gastric irritation compared to tablets due to rapid dispersion and large surface area, requiring only dissolution before absorption.
• Flexibility in compounding.
• Used both internally and externally.
• Rapid onset of action.
• Easy to carry (compared to liquid dosage forms).
• Suitable for young children and elderly patients.
• Undesirable taste is less noticeable in solid form than in solution.
• Economical to manufacture.

Disadvantages of Powders

• Not suitable for bitter, nauseating, deliquescent, and corrosive drugs.
• Inaccuracy of dose in the case of bulk powder.
• Inconvenient to carry.
• Dispensing of powder is time-consuming.
• Quantities less than $100mg$ cannot be weighed conveniently on a dispensing balance.
• Not suitable for drugs unstable in atmospheric conditions (exposure to the atmosphere or acidic pH).
• Salts of ferrous iron oxidize easily and are not suitable as powders.
• Not appropriate for potent drugs requiring small doses (e.g., variations in spoon fill).
• Time-consuming.

Method of Preparation and Dispensing

1. Reduction of particle size of all ingredients to the same range to prevent stratification.
2. Sieving.
3. Weighing of each ingredient.
4. Mixing.
5. Packaging.

Drug Powder Formulation

• Obtain powder as raw material from an original drug (animal, vegetable, or synthetic entities) using different methods of division.
• Mixing of various powders with or without excipients based on the powders’ characteristics (e.g., flow properties).
• Packaging of the finished product for easy patient use.

Methods and Equipment for Powder Preparation

• Coarse Division:
  • Cutting: Obtention of coarse fragments (e.g., vegetable drugs) - uses Blades
  • Crushing: Division of coarse fragments - uses Mortar and pestles
  • Attrition: Breaking down a substance by rubbing two surfaces together - uses Non- or stainless steel
• Comminution:
  • Attrition:
    • Laboratory scale devices: Mortar and pestle
    • Industrial scale devices: Grounding stones, Cutter mills, Sieves and screens
  • Rolling:
    • Laboratory scale devices: Roller mills
    • Industrial scale devices: Roller mills (smooth and saw-toothed cylinders)
  • Mills:
    • Attrition mills (diameter 1-2 mm)
    • Cutter mills (diameter >0.2mm)
    • Hammer mills (can be used in liquid $N<em>2$ or $CO</em>2$ to decrease the milling temperature and to protect the drug product)
    • Pebble or ball mills (diameter <2mm) (planetary pot or Jarr mills or vibration mills)
    • Micronizers or jet mills (Fluid energy mill) (diameter 1-10 µm)
    • Centrifugal impact pulverizer (diameter 0.05-2 mm)

Method of Preparation of Powders

• Calculate the quantity for one extra powder to avoid loss during weighing and mixing.
• Powder crystalline substances separately and weigh separately.
• Mix ingredients in ascending order of their weight.
• Mix thoroughly to obtain a homogenous powder.
• Weigh the required number of powders and wrap in papers.
• For hygroscopic, deliquescent, and volatile substances, use double wrapping.
• Inner wrapper: wax paper to prevent volatilization and absorption of moisture from the atmosphere.

Powder Characterization

• Particle size:
  • Influences the dissolution rate of the drug in-vivo.
  • Influences absorption rate and the onset of therapeutic activity.
  • Different particle sizes affect flow and packing properties during each event.
  • Defined during formulation and must be as uniform as possible.
  • Expressed as a number corresponding to the mesh screen size of a sieve.
  • Screen size indicates the number of openings per inch in the mesh screen.
  • Particles that can sift through a #40 sieve are said to be "40 mesh" size.

Mesh Opening Size

Powder Fineness (USP)

Particle Size Analysis

• Sieving
• Microscopy
• Sedimentation rate
• Coulter Counter
• Gas Adsorption

Flow Properties

• Important parameters in mixing and segregation phenomena during storage.
• Depend on particle size, nature of particles, shape, and moisture content.
• Determined by angle of repose, bulk or tapped density.

Excipients

• Optimal particle size distribution.
• High flowability.
• High compressibility.
• Optimal capacity for a drug.
• Physiologically inert.
• Resistant to heat, humidity, and oxidation.
• Tasteless and odorless.
• Examples: Magnesium stearate, PEG 6000, Calcium stearate, Glycerol palmito stearate, etc.

Methods of Powder Mixing

1. Mechanical Mixing
2. Hand Mixing:
   • Spatulation (spatula + tile)
   • Trituration (mortar + pestle)
   • Tumbling (wide mouth closed container)
   • Geometric dilution: Entire quantity of potent drug (x volume) + (x volume) of the diluents + (2x volume) of the diluents + (4x volume) of the diluents… repeated until all the diluents are used.

• The aim of mixing is to obtain a homogeneous association of several solid products.
• Factors influencing the mixing of powders: nature of surface, density, particle size, particle shape, particle charge, and proportion of materials
• Powders can be blended by:
  • Spatulation: for small amounts of powders, there is no reduction in particle size
  • Geometric dilution: used to help ensure that small amounts of the ingredients, usually potent drugs, are uniformly distributed throughout the powder mixture.
  • Trituration: it gives more intimate mixing than other methods. It describes the grinding of two or more substances in a mortar to intimately mix them.
  • Sifting: produce a light fluffy product.
  • Tumbling: use a large container that rotates by a motorized process.

Powder Preparation

• The manually operated procedures usually employed are:
  • Trituration
  • Pulverization by intervention
  • Levigation

Trituration

• Dry Grinding: making coarse powders into small particles by rubbing them in a mortar with a pestle.
• Used for hard, fracturable powders.
• Used to mix two dry powders.
• The circular mixing motion of the pestle on the powders contained in a mortar blends the powders and also breaks up their soft aggregates.
• By means of application of pressure on the pestle, crushing or grinding also can be affected.
• The mechanism of compression, between the flat head of the pestle and bottom of the mortar, and attrition, by the shearing action of the pestle.
• When granular or crystalline materials are to be incorporated into a powdered product, these materials are comminuted individually and then blended together in the mortar.

Levigation

• Wet Grinding: reduces the particle size of a solid by triturating it in a mortar or spatulating it on an ointment slab with a small amount of a liquid (levigations agent) in which the solid is not soluble to form a paste.
• The solvent should be somewhat viscous such as mineral oil (liquid paraffin) or glycerin, also water for an oral suspensions and the molten base for a suppository, paste or ointment.
• Used to reduce the particle size of insoluble materials when compounding ointments and suspensions.
• Liquid Paraffin is a commonly used levigations agent.
• Used to incorporate solids into dermatologic or ophthalmic ointments and suspensions to prevent a gritty feel.

Pulverization by Intervention

• Used with hard crystalline powders that do not crush or triturate easily, or gummy-type substances.
• Use an "intervening" solvent (such as alcohol or acetone) that will dissolve the compound.
• The dissolved powder is then mixed in a mortar or spread on an ointment slab to enhance the evaporation of the solvent.
• As the solvent evaporates, the powder will recrystallize out of solution as fine particles.
• Reducing the state of subdivision of solids with the aid of an additional material that can be removed easily after the pulverization has been completed.
• When it is difficult to powder a material in a mortar because it is soft or gummy, we add a second material which helps in the powdering and which is later removed.
• So when material “A” resists grinding, we add we can then grind them or pulverize them easily by adding material “B”. Then material “B” is removed.
• For example, powdering camphor is difficult, so we add a small amount of alcohol to it and we them powder it, then we allow alcohol to evaporate.
• Similarly, iodine crystals may be comminuted with the aid of a small quantity of ether.
• In both instances the solvent is permitted to evaporate and the powdered material is recovered

Packing

• Packed in sifter top containers, pressurized containers, flat metal boxes.

Labelling

FOR EXTERNAL USE ONLY

FOR INTERNAL USE ONLY

Packing Materials

• Powder Papers: Four basic types of powder paper are available:
  • Vegetable parchment: a thin, semiopaque, moisture-resistant paper.
  • White bond: an opaque paper with no moisture-resistant properties.
  • Glassine: a glazed, transparent, moisture-resistant paper.
  • Waxed: a transparent waterproof paper.
• Note: Hygroscopic and volatile drugs can be protected best by using a waxed paper, double-wrapped with a bond paper to improve the appearance.
• Parchment and glassine papers offer limited protection for these drugs.

Standards for Extemporaneous Dispensing

• Personal Hygiene
• Personal protective equipment
• Clean work area and equipment
• Appropriate work area
• Label preparation
• Weighing and measuring procedures