ceutics 4 powders and granules

a mixture of finely divided drugs and/or chemicals in a dry form

powder

powder is a special sub-class of ______

granules

powder has a greater tendency to form ___ than granules

form clumps

when are powders usually used

usually used to make other dosage forms; not in therapy

bulk medicated powders are commonly used for ______ application

topical

how does a smaller powder particle size influence the pharmaceutical properties of a drug

increases drug's dissolution rate

most common method used to determine particle size of powders

sieving

describe trituration

process of reducing particle size by grinding in a mortar and pestle

key difference between the fusion method and wet method in preparing effervescent granulation salts

fusion method involves heating the mixture, while wet method does not

describe levigation

reducing particle size by using a pad with a small amount of liquid

coarse particles are obtained after sifting powder through a mesh size of

20-40

when should one blend materials containing eutectic mixtures

when pharmacological action of the blend increases

what is the start to forming any formulation

powder

can powders be taken internally, externally, or both?

both

internal: suspensions, lung inhalation, vaccine

external: powder, cream, ointment

what are some advantages of medicated powders?

1. faster dissolution rate and absorption = rapid onset of action (compared to solid forms)

2. improved stability in dry state (compared to liquids)

3. suitable for swallowing

What steps do powders allow to be skipped for bioavailability purposes?

skips disintegration phase since it is already broken down to small unit

what are some disadvantages to powders

1. bad taste

2. hard to protect materials that are easy to melt or aromatic

3. more expensive to make sachets/ divide dose

4. more SA= more moisture absorption= unstable

what are bulk powders

Refers to powders intended to be administered in quantities which are safe for the patient to measure.

why are bulk powders non potent

higher chance of inaccurate dosing/variation, giving a large dose might be harmful

divided powders

Powders containing substances that should be administered in controlled dosage are supplied in divided dosage units

Individual doses are separately wrapped

geometric dilution

a technique for mixing two powders of unequal quantity

=ensures equal distribution of drug throughout compound

advantages and disadvantages of divided powders

1. Allows physicians to prescribe a precise amount of the drug.

2. More stable than the liquid form of many drugs.

3. Dissolve more rapidly than compressed solid dosage forms.

4. Rapid dissolution leads to faster blood levels and possibly less GI irritation.

=BUT time consuming and costly

granules

agglomerates of small particles of powder; may be used in medicine or to make other forms like tablets

advantages of granules

1. flow better than powders (this is why granules used for tableting)

2. increase compressibility

3. smaller SA than powder= more stable/ less moisture pick up

4. less likely to cake/harden

5. more uniform

6. more easily wetted than powders= used for solutions

5 things particle size can influence

DPUGS

1. Dissolution rate

2. Suspendability (ex: suspensions/colloids)

3. Uniform distribution (powders, tablets)

4. penetrability (ex: inhalers)

5. Gritiness (ointments, creams, opthalmic)

particle size grading system is based on the ________ method

sieving

sieving method

method of particle size gradation that is related to the proportion of powder that is capable of passing through the opening of standardized sieves of varying dimensions in a specified time period under shaking

what is mesh size

The number of holes in one square inch of the net

ex: 4 mesh screen has 4 openings= large particles pass through

as the number describing the mesh size increases, the particle size ________

decreases

what are the 5 particle size classifications based on USP and what mesh size number do they correlate to

1. Very coarse 2-10

2. Coarse 20-40

3. Moderately Coarse 40-80

4. Fine 80-120

5. Very Fine 120-200

3 methods for particle size determination

1. sieving method

2. microscopy

3. angle of repose

formula for calculating average diameter of particles in sieving method

diameter=

[ sum of (%retained*avg size) ] / 100

microscopic method

use of calibrated grid background to count particles

-labor intensive

angle of repose

-estimates the flow ability of a powder

- allow powder to flow through a funnel and fall freely, it will create a hill like shape. measure the angle

- a LOW angle of repose means FREE FLOW

-a HIGH angle of repose means POOR FLOW (more clumping)

what 2 factors can affect powder flow rate

1. shape= spheres flow better than needles

2. size= larger particles flow better than smaller ones

drug comminution

process of reducing particle size

why is drug communition important

comminution means reducing particle size

1. crude drug extraction

2. increase dissolution rate

3. aid in formulation of other dosage forms

4. enhance drug absorption

manual vs mechanical methods of drug comminution

manual=

1. trituration

2. levigation

3. spatulation

mechanical=

blade grinders

summarize the following

1. trituration

2. levigation

3. spatulation

1. trituration= grinding powders with mortar and pestle to reduce particle size (geometric dilution)

2. levigation= triturating a powder drug with a solvent in which it is insoluble to reduce its particle size (ointments)

3. spatulation= performed on an ointment slab with a spatula instead of with a mortar and pestle (eutectic)

spatulation

similar to levigation, performed on an ointment slab with a spatula instead of with a mortar and pestle

what is spatulation most suitable for

mixing small quantities of powders that form eutectic mixtures when in close contact

eutectic mixture

Mixture of two substances which result in a lower melting point than that of each individual constituent.

give an example of eutectic mixture

lidocaine/prilocaine

=individually, they are 2 solid substances. when combined, it becomes a liquidy oil

substances that form eutectic mixtures when combined include:

chloral hydrate, phenol, camphor, menthol, thymol

how can you avoid forming a eutectic mixture

add inert diluent such as magnesium oxide or magnesium carbonate

trituration

The process of grinding powders with mortar and pestle to reduce particle size

(ex: geometric dilution)

levigation

triturating a powder drug with a solvent in which it is insoluble to reduce its particle size

* used ot make ointments

dry granulation

forms granules without liquid (if drug is sensitive to moisture)

- roller compaction and slugging

what are the 2 dry methods for granule preparation

1. roller compaction- compacted into dry sheets then passes through granulator

2. slugging-make large tablets/slugs then granulate slugs

2 wet methods for granule formation

1. moisten powder, paste is passed through mesh, collect granules and dry

2. fluid bed processing= suspend powder in air and spray with liquid, then dry

effervescent granulated salts

granule or coarse powders containing API in a dry mixture =usually composed of sodium bicarbonate, citric acid, and tartaric acid

are effervescent granules coarse or fine

coarse to very coarse

purpose of effervescent granules

acids and bases react to make CO2 which in water masks bad taste and helps with disintegration

what is the preferred combination of products and methods used to make effervescent granules

combo of citric acid (sticky) and tartaric acid (crumbly)

=fusion method or wet method

fusion method vs wet method for effervescent tablets

fusion:

mix powders, heat, sieve and heat again

wet:

solution used as binding agent, make powders anhydrous, sieved moist granules are dried