Pharmaceutics Exam 2

pharmaceutical powder

mixture of finely divided drugs of chemicals in dry form

True or false. Powders may be used internally or externally

True

Single-dose powders

Pre measured and packaged for indiivudal use (e.g: sachets for oral reconsituttion)

Bulk powders

Large quantities for multiple doses (e.g: topical powders or bulk laxatives)

Powders

often basis for more complex dosage forms like tablets or capsules

• play a big role in solid form formulations

Powders used in many forms

• Orally 

• Via the nose as snuffs 

• Infufflations 

• Dissolved solutions 

Insufflations

powders blown into body cavity

Powders skip the _______ step

disintegration

Micromeritics

study of powder characteristics, including particle size and size distribution, shape, angle of repose, porosity, true volume, bulk volume, apparent desnity, and bulkiness

Key Properties of Micromeritics

• Particle size (Sieve analysis & Microscopy)

• Powder desnity 

• Flow characteristic (fluidity) 

Powder density

bulk density→ Light or Heavy

Flow characteristic (fluidity)

free flowing powder versus cohesive powder

• powders are good for upscale manufacturing

Powder particle size

ranges from 1 cm to 1 micrometer 

Percentage of material retained by a series of standard _______

sieves

3 mesh exmaple

largest sizse

Larger mesh number indicates ____ pore sizes in tghe sieves

smaller

Sedimentation rate 

Determined by measuring the particle settling rate in a liquid medium via Stokes law 

Sieving

the most common way to assess particle size for powders

Microscopy

particles measured against a grid

Light scattering/light diffraction

to assess if nanoparticles are made of light scattering 

Sedimentation rate

Determined by measuring the particle settling rate in a liquid medium via Stokes Law

• where we suspend these powders in a liquid media and measure how quickly or how slowly these powder particles settle in liquid media

Drug dissolution rate

smaller particles dissolve faster due to increased surface area

• smaller particle size= faster to dissolve 

• Larger particle size= longer to dissolve 

Absorption/bioavailability

Enhanced absorption can result from finer particles

Content uniformity (especially for high potency, low dose drugs)

more uniform particle sizes: even uniformity

Taste and texture:

smaller particles may influence the mouthfeel and flavor preparation

Stability

takes longer to settle→ better stability 

Flow and sedimentation rate

Larger particles improve flow, smaller particles are prone to slower sedimentation

True density

density of material itself excluding voids and intra-particle pores greater than molecular or atomic dimensions in the crystal latices

• crystalline form of the material

Granule density

density of the material incorporating intra-particulate pores greater than atomic/molecular molecules

Apparent/bulk density

density of material incorporating the voids as determined from the bulk volume and weight of a dry powder in a graduated cylinder (density of UNTAPPED sample)

Tapped density

density you have after tapping the container containing the powder (for a fixed amount of time)

• volume goes down overtime

Bulkiness

specific bulk volume

• reciprocal of bulk density

• important in powder packaging

Large particles

free-flowing

Small particles

Flow property

affected by particle size, shape, porosity and density, and surface texture

Powder flow can be analyzed by either of 3 methods

1. Angle of repose

2. Dynamic flow through circular orifice

3. Compressibility index

25-30°

Excellent flow

30-40°

Good flow 

40-45°

Fair flow

>45°

Poor flow

Angle of Repose

• simple technique for estimating flow properties of powder

• determined by allowing a powder to flow trhoguh a funnel and fall freely upon a surface

• Height and diameter of the resulting cone is measured

Powders with low angle flow ________ (larger particles), high angle flow _______ (fine particles)

freely, poorly

Dynamic flow

involves measuring th etime required to discharge a know weight of powder through orifice of known diameter

Compressibility Index (Carr’s Index)

measures the powder’s ability to decrease in volume under pressure

• differnece between bulk density and tapped density is used to calculate the index

Carr’s Index formula

PT- PB / PT x 100%

Wide difference in Cl

likely to have poor fluid properites 

Narrow difference in Cl

good flow properties

Porosity

refers to void space between particles (within packing of a powder particle)

Cubic Packing

• very porous

• Larger spaces in between

Rhombohedral Packing

• much smaller spaces 

• less porous

Non-Uniform 

smaller particles tend to fill up the voids 

• powders w/varying sizes

• tend to be more densely packed 

Polymorphism

• exist in different crystalline forms (and they have different characteristics)

• form under varying conditions e.g: temperature, solvent, time 

• can be converted from one form to another 

• only occurs solids not liquids 

X-ray diffraction, IR spectroscopy, thermal analysis, microscopy

all methods used to assess polymorphism

Polymorphs may possess different physiochemical properties

Stabilites, solubilites, rates and extents of dissolution, rates and extents of absorption, melting points

Communition

reducing the particle size

Particle size 

related to the proportion of a powder that can pass through the opening of standard sieves of various dimensions in a specified amount of time 

Large scale techniques

various mills and pulverizers (cutter, hammer, roller, fluid energy mills)

• all used in large scale manufacturing to reduce the sizes of powders

Small scale techniques

employ trituration→ mortar and pestle, pulverization, levigation, spatulation

Trituration

grinding powder into mortar and pestle→ reducing the drug substance to smaller particles

• important for extemporaneous compounding

Pulverization

using a volatile solvent (like alcohol) to help reduce the size of the particle 

• most for gummy substances or sticky substances

• helps us to mill the material

• volatile substance evaporates 

Levigation

aim is to reduce particle size, but we add an insoluble solvent → causes suspension of particles

• allwos particles to be further grinded

• THE SOLVENT DOES NOT DISSOLVE

• e.g: mineral oil and glycerin