Powders Flashcards
Powder
A dry, solid substance composed of finely divided particles
- made from crushing, grinding or comminuting
- type of dosage form
Pharmaceutical Powder
dosage forms of a solid or mixture of solids reduced to a finely divided state and intended for internal or external use
Granules
prepared agglomerates of powdered materials
Powders have been used
- Orally
- Via the nose as snuffs
- Insufflations- powders blown into body cavity
- Dissolved/ solutions for topical and oral use or use as douches
Benefits for powders
- Easy alteration of quantity of drug dose
- Useful for children and individuals who cannot swallow tablets/ capsules
- Provide rapid onset since absorption is not dependent upon disintegration, only dissolution of material
- more stable than liquid dosage forms
Size distribution affetcs
- Dissolution rate
- Absorption
- Stability
- Texture and taste
- Flow and sedimentation rates
Polymorphism
ability of a solid material to exist in more than one form or crystal structure
- only exist in solid state and do not exist in solution
- Can be checked by various techniques to verify and establish purity
- Polymorphs may possess different physiochemical properties such as stabilities, solubilities, rates of dissolution and melting points
Dissolution
As a particles dissolves
- surface molecules are the first to enter into solution
- Saturated drug layers forms on surface known as diffusion layer
- Drug passes diffusion layer into the dissolving fluid
- Upon contact with membranes, absorption occurs
Dissolution rate
- time it takes for drug to dissolve, especially at absorption site
- controls overall bioavailability
- rate may be increased by decreasing particle size and/ or viscosity of medium
Steps in preparing a powder formulation
- Obtain raw material
- Analyze material (characteristics): Size, chemistry. Particles of all ingredients should be similar in size
- Weigh
- Sieve
- Blend
- Package final product
Micrometrics
science of small particles
Examples of Micrometrics
- particle size and distribution
- angle of repose
- porosity
- void and bulk volume
Sieving
particles are passed by mechanical shaking through a series of sieves of known and successively smaller size
Other techniques for separating size
Microscopy- Particles measured against a grid
Light scattering/ Light diffraction
Sedimentation rate- Determined by measuring the particle settling viscosity in a liquid medium via Stokes Law
Powder particle size ranges from
very coarse (1cm) to extremely fine (1um) - usually can be easily characterized by the % of material retained by a series of standard sieves
Angle of Repose
simple technique estimating flow properties of a powder
- determined by allowing a powder to flow through a funnel and fall freely upon a surface
- Height and diameter of the resulting cone is measured
Angle of repose equation
tan(o)= height of powder cone/radius of cone = h/r
- Powder with low angle flows freely
- Powders with high angels flow poorly
Porosity
ratio of volume of interspaces to the volume of the mass
- Packing depends on particle shape w void spaces between particles
- if particles are not uniform, smaller particles may fit into spaces between the large particles and decrease void spaces
Apparent or bulk density ( untapped density)
- Density of material including pore and voids (true volume +porosity)
pa= m/ Vbulk
Tapped density
ratio of powder bed mass to powder bed volume obtained by mechanically tapping a graduated cylinder containing sample until little to no further volume change is seen
p/ m/V
Particle reduction
increases particle number and total surface area
- Particle size and shape in a powder is irregular
Coarse division
Reducing large particle into fragments of different sizes by cutting, crushing or attrition
Communition
Process of reducing particle size
Trituration
Grinding or pulverizing powders to create fine particles with a mortar and pestle
Process of reducing particle size
- Powder blending technique
Levigation
commonly used in small scale preparations or ointments and suspensions
-A paste is formed with a liquid ( levigating agent) that the powder is insoluble in
Glycerin and Mineral oil are common levigating agents
Blending powders
1st step for uniform mixing
- Best to reduce particle size of components to obtain a homogenous mix
Factors that influence powder blending
Amount of ingredients Density Surface area Particle size Particle changes Powder flow
Geometric dilution
Homogenous mixture of two or more substances in widely different amounts
- Smallest quantity of active ingredient is mixed thoroughly with equal amount of diluent; repeated until all material is mixed
Spatulation
Combining and mixing by means of a spatula
- Generally on a piece of paper or ointment slab/tile
Segregation
Demixing - components tends to separate out
-Can result in content variation and unacceptable products Usually due to particle size variation
Approaches to minimize segregation
- selection of narrow size fraction range
- selection of excipients with density similar to active
- granulation of powder mix to uniform distribution
Hygroscopic powders
will absorb moisture from the air
Deliquescent powder
powders that may absorb moisture from the air to the extent that they will partially or completely liquify
Efflorescent powders
A crystalline powder that contains water of hydration or crystallization
-Powder may become sticky and pasty or even liquify
Eutectics
powders that become sticky or pasty or liquefy when mixed together
- To avoid this problem, you can mix material w a bulky absorbent powder
- Powders should be mixed with a spatula rather than a mortar and pestle to avoid compression
Explosive mixtures
Some combination of powders react when mixed
-These are most commonly oxidizing and reducing agents
Approaches to minimize efflorescent powder problems
Use anhydrous form, use a bulky drying powder, avid compacting method
Desiccant packs are used to
absorb moisture and keep things dry
- dispensing medications in tight containers with these packs
Incorporation of liquids
Liquids can be absorbed into an inert powder that is then geometrically incorporated into the powder bulk
- Add material in alcohol and spray it evenly on powder. This will allow the solvent to evaporate leaving the ingredient evenly dispersed
Medicated powders
- Oral after mixing powders
- Aerosol Powders
- Topical powders
- Dry powder inhalers
Oral after mixing powders
-Suspensions
Can be mixed with water or infant formulas or soft foods
Preferred route for people who have trouble swallowing solid dosage forms
-Ex: Laxatives, Analgesics, Antibiotics- Provided as a powder to be reconstituted with water
Aerosol Powders
Insufflation is the act of “blowing” or inhaling something into a body cavity
- Finely divided powders
- Applied to a body cavity- Ear, nose, tooth socket, throat, lung, vagina, rectum
Dry Powder inhalers (DPI)
- Also called Metered Dose inhalers (MDIs)
- Oral administration via inhalation
- Micronized particles delivered in accurate metered quantities
- Particle size range: 1-6 um in diameter
- Drug delivered deep into lungs
- Contains inert propellants and diluents with the API
- Mostly for treatments of asthma
Topical powders
- Should have a uniform, small particle size
- should not irritate the skin when applied
- should adhere to skin
Divided powders
- After a powder has been properly blended, it may be divided into individual dosing units based on the amount to be taken or used at a single time
Ex: PEG 3350 (MiraLAX)
Granules
- dosage form compsoed of dry aggregates of powder particles
- Usually irregular shaped, but may be prepared to be spherical
- May be swallowed directly, dispersed in food or dissolved in water
- May be compacted into tablets or filled into capsules with or without additional ingredients
Granules advantageous characteristics
- lower surface area for better flow
- more stable in air
- minimizes powder segregation
- less likely to cake upon setting
- more easily wetted than powders
Wet method 1 ( granules)
- Moisten powder
- Resulting aggregate is passed through a screen sieve to produce desired size granules
- Granules are placed on drying trays and dried by air or heat in drying ovens
Wet method 2 (granules)
- Particles in a conical tower are vigorously dispersed and suspended while a liquid excipient is sprayed on the particles
- Product is dried which forms granules of pellets of defined size
Dry method 1 (granules)
Roll compaction
- Dry powder is passed through a roller compacter and then through a granulated machine, usually in an integrated system
Dry method 2 (granules)
Slugging
Dry powder is compressed into large tablets or slugs under 8-12,000 lbs. The pressure comes from using a compression machine (tablet press)
2. Slugs are then into the desired size
Effervescent granulated salts
- tablet or granule dry mixtures containing a medicinal agent, citric acid, tartaric acid, and sodium bicarbonate
- It rapidly release CO2 when in contact with water
Advantages of effervescent formulations
- resulting carbonated solution can mask flavors
- protects low pH sensitive materials in stomach
- Assists in delivering large doses
- No need to swallow tablets
- Enhanced absorption of some active drugs
Effervescent tablets and granules must be
dissolved in water, not swallowed directly
Dry/fusion method (effervescent)
One molecule of water acts as the binding agent for the powder mixture
- All preparations are done in low humidity environment and in stainless steel vessels
- Powders are sized and blended and sieved to ensure uniformity
- Mixture is then moved to drying ovens at 34-40˚C which releases water which dissolves some material and binds mixture
- Mixture is then sieved to produce granules of desired size and then dried at a temp kept less than 54˚C before packaged in tightly sealed containers
Wet method (effervescent)
Binding water is from a moistening agent
Manufacture can be done is reaction vessels like V-blenders
- Once enough moistening agent is added, the procedure is the same as dry method
- The granules are prepared and dried and either packaged as product or further processed into tablets
- Lastly, the material is then packaged appropriately protected from moisture
Patient needs to be instructed to allow
for the reconstitution of granules to ensure complete wetting of all ingredients with sufficient time and agitation to allow the soluble components to dissolve
