Powders

Powder

used as pharmaceutical dosage forms may contain one or more drug substances and can be used as is or can be mixed with a suitable vehicle for administration

Powders

are defined as a single solid or a mixture of solids in a finely divided state

Granules

solid dosage forms that are composed of agglomerations of smaller particles

Granules

These multicomponent compositions are prepared for oral administration and are used to facilitate flexible dosing regimens as granules or as suspensions, address stability challenges, allow taste masking, or facilitate flexibility in administration (for instance, to pediatric patients, geriatric patients, or animals)

capsules or compressed into tablets

Most powders & granules are filled into …

agglomeration

clumps/ aggregates made up of smaller particles

Bulk powder

powder/granule in a jar that gets scooped, put into a liquid to create a suspension and proceed to drink

Unit dose

divided powders (small packets) for a drink

Powder for solution/suspension

powder that you place in the mouth and when drinking, turns into a solution or suspension.

Particle size distribution

is the quantitative measure of different particle sizes in the powder

Sieve analysis, Microscopy, Automated powder analysis

The methods for particle size measurement includes …

Particle size distribution

Considered the most important property of powder

Sieve Analysis

Can be used to determine the particle size distribution of a sample

Sieve Analysis

used to remove excessively large or small particles from a starting material or blended mixture before packaging or further processing

45-150

Based on the table, most of the grams are retained under what particle diameter?

Zero open size to collect the rest

What is the point of the pan in the sieve?

Microscopy

Shape parameters

Combined with image analysis

Dynamic image analysis

Size & shape parameters

dry/dispersed in a liquid

Powders and granules

must flow through pipes/tubes in manufacturing and packaging

Powder

must not get impacted nor segregate

glidant

needed to improve flow of the mixture

Rat-holing

impacts a small center of the tube that is actually moving; partial impaction

glidant

sliding/moving; improving powder flow

Silicon dioxide

it helps particles move pass each other (most common glidant)

talc

associated w/asbestos(terrible material that cuases health issues)

glidant

Silicon dioxide & talc are examples of what?

Granules

tend to flow well without glidants added

FlowLac 100

Which of the options in the image contains the best flow rate

spherical shape & smaller size

What makes the FlowLac100 better than the other options?

particle size distribution

flow size is dependent on what?

granules

What would have better flow in this setup?

Blending

is the process of different powders dispersing throughout a mixture

Blending

Strongly affected by the flow properties of each individual powder

uniformity of a powder blend

an acceptable range of component concentrations for a given sample size

uniformity of a powder blend

e.g. ± 2% of the desired concentration of each component for 500 mg sample

e.g ± 0.5% of the desired concentration of each component for a 10 g sample.

are examples of

greater

Variability in the concentrations of each component is ____ when comparing small sample sizes, e.g. 10 mg of blend

variability

E.g. mix two powders and fill into capsules with total weight 30 mg vs 300 mg

demonstrate what idea

Comminution, mortar & pestle, grinding mill

Powder can grinded through what methods?

Spatulation, mortar and pestle, bench scale V-blender, centrifugal blender

Pharmacists accomplish small scale blending:

grinding mill

electric device that grinds to the chosen size pharmacists want

comminution

grinding / particle size reduction; only for manufacturing.

spatulation

spatula that mixes particles

V blender

2 cubes that form a V, creating a shaft blender that inverts and mix particles

Centrifugal

centrifuge with the powder in the jar followed by spinning & mixing

Geometric dilution

Method to disperse a small amount of one powder throughout a much larger mixture

May be used with a mortar and pestle or a mechanical mixer

Add drug powder to mortar

Add an equivalent amount of diluent and mix well

Add another equivalent amount of diluent to the mixture in the mortar

Repeat until all diluent is added and the whole mass is mixed well

the following describes the process for geometric dilution

homogeneity

A small amount of an appropriate dye can aid blending, this implies visual cue for …

doubles up

What happens to the total mass within each step?

Compressibility

Important powder property for tablet and capsule manufacturing

binder

something that holds the mixtures together whether as a powder or something else that compresses well.

Dissolution rate

= DSC_s/h describes what equation?

surface area (S)

∝ ¹/_r (relates to the radius) describes what equation?

surfactant

What may be required for the API particles to disperse in water

larger surface area

Smaller particles will tend to have …

Powders

susceptible to atmospheric humidity

hygroscopic

Absorb water vapor from the air onto the particle surface

Room humidity, surface area of powder

Water vapor adsorption depends on

Effervescent

products tend to be hygroscopic

room humidity, surface powder area

Water vapor absorption increases with more

as humidity increases, water increases

The photo demonstrates what relationship between humidity & water?

Deliquescent solids

adsorb enough water vapor from the air to form liquid droplets and dissolve

Hygroscopic & deliquescent materials

materials have potential stability issues if they are stored in a humid environment, not tightly closed, etc

Physical stability

Caking

Product may become wet/moist

Chemical stability

Adsorbed water molecules may cause hydrolysis of the drug

Effervescent salts may react to release CO2

watertight & airtight as possible

Powder packaging must be …

cool, dry areas

Where should store powders and solid dosage forms be placed?

Bulk powders

close container quickly after measuring the dose

Desiccant

preferentially adsorbs water to decrease the amount that adsorbs onto the drug product.

Caking

when molecules thicken and become hard to flow

Advantages

Oral doses are easily customizable

May be administered with patient’s preferred flavored liquid

Lower shipping cost than liquids

Solids tend to be more stable than liquids (esp. antibiotics)

Unit dose products are portable

the following describes

Disadvantages

Bulk powders require dose measurement

Packaging must protect product from humidity

Oral – flavoring required

Fine powders can be easily aerosolized and accidentally inhaled

the following describes

surface area, hygroscopicity, tendency to aersolize

Compared to powders, granules have lower

compression & flow

Compared to powders, granules have better

dissolving and wetting

Compared to powders, granules are faster at

Diluent

Increase mass of powder

More accurate dose measurement for potent drugs

Oral & topical

Diluents are for what products?

Oral Diluents

Lactose, sucrose, mannitol, maltodextrin, microcrystalline cellulose

are examples of …

Topical Diluent

Talc, cornstarch are examples of …

Granulating agent

helps hold granules together

Granulating agent

sugar/polymer solution are examples of what?

Water/solvent

What is used to apply the granulating agent?

Disintegrating agent

promotes powder or granule dispersion in water

dry particles

Solvent is evaporated later on to produce …

Wetting agents

surfactants that improve water & disperse

glidant

Colloidal silicon exist in the following image as

granulating agent

Guar Gum is included in the image shown as a …

diluent

mannitol & microcrystalline cellulose is included in the image shown as a …

sweetener

sucralose is included in the image shown as a …

sweetener

FLAVORED COLESTID is orange flavored and light orange in color. One dose (1 packet or 1 level scoopful) of FLAVORED COLESTID is approximately 7.5 grams powder which contains 5 grams of colestipol hydrochloride. This product also contains the following inactive ingredients: aspartame, beta carotene, citric acid, flavor (natural and artificial), glycerine, maltol, mannitol, and methylcellulose.

In the description above, aspartame is used as a …

flavor

FLAVORED COLESTID is orange flavored and light orange in color. One dose (1 packet or 1 level scoopful) of FLAVORED COLESTID is approximately 7.5 grams powder which contains 5 grams of colestipol hydrochloride. This product also contains the following inactive ingredients: aspartame, beta carotene, citric acid, flavor (natural and artificial), glycerine, maltol, mannitol, and methylcellulose.

In the description above, citric acid is used as

cosolvent

FLAVORED COLESTID is orange flavored and light orange in color. One dose (1 packet or 1 level scoopful) of FLAVORED COLESTID is approximately 7.5 grams powder which contains 5 grams of colestipol hydrochloride. This product also contains the following inactive ingredients: aspartame, beta carotene, citric acid, flavor (natural and artificial), glycerine, maltol, mannitol, and methylcellulose.

In the description above, glyverin is used as

diluents

FLAVORED COLESTID is orange flavored and light orange in color. One dose (1 packet or 1 level scoopful) of FLAVORED COLESTID is approximately 7.5 grams powder which contains 5 grams of colestipol hydrochloride. This product also contains the following inactive ingredients: aspartame, beta carotene, citric acid, flavor (natural and artificial), glycerine, maltol, mannitol, and methylcellulose.

In this description, maltol & mannitol are used as …

granulating agent

FLAVORED COLESTID is orange flavored and light orange in color. One dose (1 packet or 1 level scoopful) of FLAVORED COLESTID is approximately 7.5 grams powder which contains 5 grams of colestipol hydrochloride. This product also contains the following inactive ingredients: aspartame, beta carotene, citric acid, flavor (natural and artificial), glycerine, maltol, mannitol, and methylcellulose.

In this description, methylcellulose is used as …

granulating agent

Azithromycin for Oral Suspension, USP is supplied in bottles containing azithromycin monohydrate powder equivalent to 300 mg, 600 mg, 900 mg, or 1200 mg azithromycin per bottle

and the following inactive ingredients: sucrose; tribasic sodium phosphate anhydrous; hydroxypropyl cellulose; xanthan gum; colloidal silicon dioxide, FD&C Red #40; and artificial cherry flavor

Colloidal silicon dioxide is used as

sweetener

Azithromycin for Oral Suspension, USP is supplied in bottles containing azithromycin monohydrate powder equivalent to 300 mg, 600 mg, 900 mg, or 1200 mg azithromycin per bottle

and the following inactive ingredients: sucrose; tribasic sodium phosphate anhydrous; hydroxypropyl cellulose; xanthan gum; colloidal silicon dioxide, FD&C Red #40; and artificial cherry flavor

Sucrose is being used as …

antioxidants

Azithromycin for Oral Suspension, USP is supplied in bottles containing azithromycin monohydrate powder equivalent to 300 mg, 600 mg, 900 mg, or 1200 mg azithromycin per bottle

and the following inactive ingredients: sucrose; tribasic sodium phosphate anhydrous; hydroxypropyl cellulose; xanthan gum; colloidal silicon dioxide, FD&C Red #40; and artificial cherry flavor

Xanthan gum is being used as

accurate measurements, mix w/liquid or food, take entire dose

With oral, solution,and suspension administration, it is important to …

shake

For suspensions, it is especially important to…

spread over affected area

For topical administration, it is important to …

cool dry area away from humidity

Powders & granules can be stored where?