powders and granules slides

what is a simple powder?

a single chemical substance in powder form

what is a pharmaceutical powder?

a mixture of finely divided solids in dry form

• particle size: 0.1 to 1000µm, most commonly 0.1 to 10µm

what is a granule?

a prepared agglomerate of smaller particles of powder

• agglomerate: a cluster of something (powdered material in this case)

what are characteristics of powders and granules?

• may be very fine, coarse, or of intermediate particle size

• used internally and externally

• dispensed as bulk or divided powders/granules

what are the advantages of powders and granules?

• stability: higher due to dry form

• administration: easy and convenient for larger doses

what are the disadvantages of powders and granules?

• taste: problems with bitter tasting and moisture sensitive drugs

• packaging: difficult especially for divided powders

is there limited use of powders in therapeutics?

yes, there is a limited use of medicated powders in therapeutics, but extensively used in the preparation of other dosage forms

how should you interpret this?

as sieve number increases, sieve opening decreases (becomes smaller)

• the larger the sieve #, the smaller the particle size

what is a very coarse powder by USP sieve category?

all passes through sieve #8, no more than 20% passes through sieve #60

what is a coarse powder by USP sieve category?

all passes through sieve #20, no more than 40% passes through sieve #60

what is a moderately coarse powder by USP sieve category?

all passes through sieve #40, no more than 40% passes through sieve #80

what is a fine powder by USP sieve category?

all passes through sieve #60, no more than 40% passes through sieve #100

what is a very fine powder by USP sieve category?

all passes through sieve #80

what are the five effects of particle size?

• dissolution rate

• suspendability

• content uniformity

• inhalers

• grittiness

what is the effect of particle size on dissolution rate?

micronized drugs have higher dissolution and bioavailability

what is the effect of particle size on suspendability?

rate of settling can be reduced by using finer particles

what is the effect of particle size on content uniformity?

dose variation can be reduced by using uniform size of particles

what is the effect of particle size on inhalers?

only fine particles reach deep in the respiratory tract

what is the effect of particle size on grittiness?

coarse particles may cause grittiness in dermal ointments, creams and ophthalmic preparations

what is comminution, and what are the three main methods for particle size reduction?

comminution is the reduction of a solid substance to a finer state

1) trituration

2) levigation

3) pulverization by intervention

what is trituration?

comminution in dry state

• a rough surface (porcelain mortar) is more effective than a smooth surface (glass mortar)

what is levigation?

comminution with the aid of a liquid (levigating agent ex: glycerin and mineral oil) in which the powder is insoluble

what is pulverization by intervention?

comminution with the aid of a volatile liquid

• useful for rubbery substances such as camphor

what is used to measure the flow properties of powder/granules?

angle of repose (𝚹)

tan 𝚹 = h/r

how is angle of repose (𝚹) determined?

determined by allowing powders/granules to flow through a funnel and fall freely onto a surface

what does a smaller angle of repose indicate?

better flow properties

what does a larger angle of repose indicate?

poorer flow properties

what are bulk powders?

powders dispensed in bulk quantities, for non potent drugs

• generally stored at room temperature, in a clean and dry place

what are examples of bulk powders for internal use?

antacids, laxatives, douche powders

what are examples of bulk powders for external use?

anti-infectives, antifungals, dental cleaning powders

what are divided powders?

potent medication powders available as divided powders or can be dispensed by pharmacists

• divided into individual dosing units based on the amount to be taken or used at a single time

what are aerosol powders used for?

used to treat asthma or other bronchial disorders

• dry-powder inhalers (DPIs)

• metered-dose inhalers (MDIs)

What components are required when formulating aerosol powders for use in Dry-Powder Inhalers (DPIs)?

micronized powders and pharmaceutical diluents

What components are required when formulating aerosol powders for use in Metered-dose inhalers (MDIs)?

micronized powders, inert propellant (ex: hydrofluoroalkanes [HFA]), pharmaceutical diluents

what are medicated powders used for externally?

dusted on the affected area from sifters or powder aerosols

what are examples of internal local effect powders?

laxatives, antacids, etc.

what are examples of internal systemic effect powders?

analgesics, antibiotics, etc.

for medicated powders, can all drugs be formed into tablets and capsules?

no, some doses of some drugs are too bulky to be formed into tablets or capsules

how should medicated powders be taken?

it can be taken with liquids or soft foods

for medicated powders, what kind of drugs are dispensed as oral or injectable powders for reconstitution?

unstable drugs

• ex: antibiotics for children

what is blending?

mixing of two or more powders?

what is spatulation?

blending small amounts by spatula on sheet of paper or ointment tile

is spatulation suitable for potent substances or large quantities of powders?

no

• it is however suitable for eutectic mixtures (only very little force is needed)

what is trituration used for in powder blending?

used to comminute as well as blend powders

what is geometric dilution used for?

used to ensure uniform distribution, especially in case of potent drugs

what is the point of adding inert colored powder?

it is used to permit visual inspection of the mixing process

what is sifting in blending of powders?

powders are passed through sifters

• it makes light, fluffy products

is sifting suitable for mixing potent drugs?

no

what is tumbling in blending of powders?

there is tumbling (mixing of powders) in a rotating chamber

• both small-scale and large-scale mixing

is tumbling suitable for mixing potent drugs

yes

what are the features of granules?

• better flow properties than powders

• more resistant to atmospheric humidity

• less likely to cake or harden upon standing

• easy to wet compared to powders

• granules often preferred for dry product intended to be constituted into solutions or suspensions

what are examples of a commercial preparations: antibiotic granule products?

Amoxil, Keflex, Biaxin dry suspension

Lactinex is listed as commercial preparations. what is it used in?

used in uncomplicated diarrhea, including that due to antibiotic therapy

what are effervescent granules?

a special form of granules to provide a pleasant vehicle for drugs with bitter or salty taste

what ingredients make up effervescent granules?

contains mixtures of citric acid, tartaric acid combined with sodium bicarbonate

• in the presence of water, this mixture liberates CO2 resulting in effervescence

• the resulting carbonated solution masks undesirable taste of any medicinal agent

• effervescent preparations: E-Z-Gas granules, Zantac 25

why is a combination of citric and tartaric acids preferred over a single acid?

citric acid makes sticky mixture, which makes it difficult to granulate. tartaric acid are granules that are readily lose their firmness and crumble.

what is the ratio of mixture containing citric acid and tartaric acid given for the desired effervescent effect?

1:2

how are the ingredients prepared and combined in the first step of the dry (fusion) method?

citric acid crystals are powdered and mixed with other powders (same sieve size, including the drug)

for dry or fusion method, why must the powders be mixed rapidly in a low-humidity environment?

to prevent moisture absorption and premature reaction

for dry of fusion method, at what temperature must the mixture be placed in the oven at to release water of crystallization from citric acid?

34-40°C

for dry of fusion method, what role does the released water of crystallization play in the mixture?

it dissolves a small portion of the powder, acting as a natural liquid binder

for dry or fusion method, what forms after binding, and what sieve numbers are used to size the granules?

spongy mass is formed, which is passed through sieves to create granules of specific sizes (#10 for small, #8 for medium, and #4 for large)

for dry or fusion method, what is the maximum drying temperature for the finished granules before they are packed?

granules are dried at ≤54°C before packaging

for the wet method, what serves as the binding agent instead of water of crystallization?

an aqueous alcoholic solution

for the wet method, what does the binder do?

it produces a pliable mass suitable for granulation

for the wet method, what kind of powders are used?

all anhydrous powders

for the wet method, how much moisture is added to achieve proper consistency?

only a small amount of moisture

what happened once the wet method is finished?

the granules are then prepared and dried as in the fusion method

if a drug powder is allowed to pass through the following stacked sieves (in the order listed below), maximum amount of very fine particles will be retained by sieve # ____________.

a) sieve # 2.0

b) sieve #20

c) sieve # 100

d) sieve # 200

d

which of the following is not used for particle size reduction?

a) trituration

b) levigation

c) spatulation

d) pulverization by intervention

c

which of the following powder blending methods will also result in particle size reduction?

a) spatulation

b) trituration

c) sifting

d) tumbling

b