Powders and Granules

Powders

• Powders can be amorphous or crystalline solids and are used to describe the physical form of finely divided particles or as a type of pharmaceutical preparation for internal or external use
• Powders are dosage forms composed of solids or mixtures reduced to a finely divided state for internal or external use

Granules

• Granules, used as dosage forms, consist of aggregated powder particles forming larger particles, typically 2-4 mm in diameter
• Granules are larger than those prepared as an intermediate for tablet manufacture

Advantages of Powders

• Powders allow flexibility in medication quantity, unlike standardized capsules or tablets, and facilitate dose adjustments in clinical studies
• Doses can be individually weighed and packaged in powder papers, envelopes, or vials
• Powders are suitable for infants and young children who cannot swallow tablets or capsules, as they can be mixed with food
• Powders offer a rapid onset of action due to their dispersibility and large surface area, requiring only dissolution before absorption
• Powdered drugs can be blended with fillers and other ingredients to create solid dosage forms, liquid dosage forms, and semisolid preparations

Physicochemical Considerations

• Solid materials are characterized by morphology, purity, solubility, flowability, stability, particle size, uniformity, and compatibility with other formulation components before use in pharmaceuticals
• Adjusting and controlling a drug's particle size ensures efficient production and optimal therapeutic efficacy

Particle Size

• Pharmaceutical powder and granule particles range from extremely coarse (10 mm) to extremely fine (1 µm or less)
• The particle size of a powder is characterized using descriptive terms defined by the United States Pharmacopeia (USP)

USP Descriptive Terms for Particle Size

• Very Coarse: all particles pass through a No. 8 sieve, with no more than 20% passing through a No. 60 sieve
• Coarse: all particles pass through a No. 20 sieve, with no more than 40% passing through a No. 60 sieve
• Moderately Coarse: all particles pass through a No. 40 sieve, with no more than 40% passing through a No. 80 sieve
• Fine: all particles pass through a No. 60 sieve, with no more than 40% passing through a No. 100 sieve
• Very Fine: all particles pass through a No. 80 sieve, with no limit to greater fineness

Influence of Particle Size

• Dissolution Rate: Micronization increases drug dissolution and bioavailability
• Suspendability: Fine dispersions (0.5 to 10 μm) maintain uniform dispersion in liquid vehicles
• Dose Uniformity: Uniform distribution in powder mixtures ensures consistent dosing
• Penetrability: Particles 1 to 5 µm penetrate the respiratory tract deeply when inhaled
• Lack of Grittiness: Fine powders (50 to 100 µm) reduce grittiness in dermal and ophthalmic preparations

Micromeritics

• Micromeritics studies several characteristics of small particles, including size, distribution, shape, angle of repose, porosity, true volume, bulk volume, apparent density, and bulkiness

Angle of Repose

• Angle of repose is used to estimate the flow properties of a powder
• It is determined by allowing a powder to flow through a funnel onto a surface, measuring the height (h) and radius (r) of the cone, and calculating the angle using the formula: θ = h/r
• Powders with low angles of repose flow freely, while those with high angles flow poorly

Flowability

• Excellent: <20 degrees
• Good: 20-30 degrees
• Passable: 30-34 degrees
• Very Poor: >40 degrees

Factors Determining Flow Properties

• Shape: Spherical particles flow better than needles
• Size: Particles of 250 to 2,000µm flow freely, particles of 75 to 250 µm may flow freely depending on shape, and particles smaller than 100 µm have flow issues

Particle Size Reduction (Comminution)

• Crude drug extraction
• Increase drug disollution
• Help for pharmaceutically acceptable dosage
• Increase drug absorbtion
• Increases surface area

Manual Comminution Methods

• Trituration: Reduces particle size by rubbing with a mortar and pestle, utilizing pressure and attrition. It may require side scraping with a spatula

Levigation

• Levigation reduces size and grittiness, involving a mortar and pestle or ointment tile
• In Levigation, a paste is formed by combining the powder with an insoluble liquid (levigating agent), then triturated; mineral oil and glycerin are common levigating agents

Pulverization by Intervention

• In pulverazation by intervention, the method reduces particle size with a second agent that is readily removed
• This method is used for substances like camphor, where alcohol or volatile solvents aid trituration, then evaporate, leaving the pulverized product

Modern Comminution Method

• It reduces particle size using rapidly moving blades within a chamber.
• The system protects the environment from chemical dust, reduces product loss, and prevents contamination

Special Methods Particle Size Reduction

• Freeze Drying (Lyophilization): Removes water from frozen products via sublimation at -10 to -40°C; used for heat-labile biologicals like blood serum and penicillin
• Spray Drying: Converts solutions or suspensions into dry, free-flowing powders in one step, atomizing the liquid into heated air, creating spherical droplets that dry instantly

Blending Powders

• Reduce the particule of each substance before blending for uniform mixture
• Powders can be blended by spatulation, trituration, sifting, and tumbling, depending on the ingredients and equipment

Spatulation

• Spatulation is for blending small powder amounts on paper or an ointment tile
• It is unsuitable for large quantities or potent substances due to uncertain homogeneity; suited for mixing eutectic mixtures

Trituration

• Trituration can both triturate and mix powders. Glass mortars are prefered when mixing wihout comminution
• Geometric dilution is used for ensuring uniform potent drug distribution

Geometric Dilution

• Used when substnaces have similar color
• Placing an appprox equal quanity to a potent drug in a mortar. Then triturate, add again, then triturate and repeat
• Sometimes add colored powder as a visual indication

Sifting (Sieving)

• When powders pass through sifters
• For light, fluffy products
• Not for potent ingredient distribution

Tumbling

• Chamber rotates and mixes powders
• Thorough but very time consuming
• Widely used is industry, blends with motoriesed blades and a large vessel

Problems in Particle Size Reduction

• Undesirable material separation from different components due size and density,

How particle size reduction occurs:

• Sifting or percolation can occur
• Fine aeration powders with different sizes and density can move around
• Fine particles are kept suspended for longer, dusting

Best Practice

• Reduce steps and drop heights
• Dust Control
• Fluidation control
• Use slow fill transfer rates
• Vent appropriately
• Baffles

Medicated Powders

• Used both internally are externally

Internal Medicated Powders

• Usually taken orally with water/infant formula, they can be inhaled for systemic and local effects
• Sometimes, mixed with sterile water

Orally Administered Powders

• Effects can be both local and systemic, (laxative, anagesic)
• Usually prefrable for solids
• Sometimes bulcky and must be formed as powder

Aerosol

• Sometimes are administered through dry inhalers which contain micornized medication,
• DPI are inhaled as fine particles
• Used for athsma

Nasal

• Inhailed through nasal cavity
• Best used for when rapidly absorbed via respiratory rout

External powders

• Dusted on infected are directly
• Should ONLY be for external use
• Free from grittines and used for therapeutic, prophylactic or lubricant purposes

Dispensing

• Can be bulk and divided

Bulk Powders

• These are generally prepackaged
• Like antacids and laxative
• Douche powders
• Medicateds for exernal applications
• Brewers powders and vitain supplements
• Educate customers for handling, storing
• Instructions how to measure the power, also which liquid

Divided

• Once blended using geometric dilution
• Placed individually on a small peice of paper
• Can be pre made/ pre measured
• Depending on substance, you weigh each item before enfolding in paper
• Paper is hygroscipic, always store well

Granules dosage forms

• Ingredients may segrate due t particle diiferences
• Must use non uniform product as the patient may nt gfet the correct does
• Granules: robust enough to with stande haandling

Advantage

• Flows better than powder
• More compressible
• Stable physically
• Easly wretted by sovlent
• Production consistent sizes thus content uniform

Examples

• Certain antibiotics/antibiotics are unstable in aqeuous solution, needs prified water
• Used medicianal agents with colorants and flavoring
• Sprinkled on food or eaten plain

Preparation

• Wet or dry

Wet Method

• Water to powder and liquid
• Squeeze through screen to desired size
• Placed on drying trays and dry/heat it out
• Periodic movement to prevernt adhestion
• Screening stage again

Dry Method

• Through roll compactor than granualting mahcine
• Under 8-12,000 lb of pressure
• Flat face and 2.5 cm
• The dry process often results in the production of fines, that is, powder that has not agglomerated into granules.
• These fines are separated, collected, and reprocessed

Efferescent Granual Salts

• rapid carbondiozxides in ocntact with water
• dissolves befire ingestion
• The resulting carbonated solution masks undesirable taste of any medicinal agent.
• prevents uncontrollable efervescences

Mixture

• Citiric and Tartaric
• tartrate causes crmubling problems
• The ratio of the effervescent ingredients is 1:2:3.4 for the citric acid: tartaric acid: sodium bicarbonate.

Prep method

• Dry or fusion or wet

Fusion (Dry Method)

• Water in citric act as binding aget
• Use stainless steel or resisatnt matieral to acids
• Don't absrob mositrue to rpevent chemical reacttions
• 34-40 celcius with acid spatula to turn powder
• After bread dough, remove and sruhb through seive
• Dry a temperature exeeeding 54 and conatins tightly

Wet method

• Wet method differs from the fusion method in that the source of binding agent is not the water of crystallization from the citric acid but the water added to alcohol as the moistening agent, forming the pliable mass for granulation.
• Anhydrous all along as long as added liquid