CHAPTER 6 POWDERS & GRANULES

41 Tecson42 Tuazon43 Ubana

POWDERSphysical form: a dry substance composed of finely divided particles. type of pharmaceutical preparation: medicated powder intended for internal or external use.

•Powders are intimate mixtures of dry, finely divided drugs and/or chemicals that may be intended for internal or external use.

• the use of medicated powders in preparation of other dosage forms is extensive.

may be blended with powdered fillers and other pharmaceutical ingredients to fabricate solid dosage forms as tablets and capsules

• the use of medicated powders in preparation of other dosage forms is extensive.

may be dissolved or suspended in solvents or liquid vehicles to make various liquid dosage forms.

• the use of medicated powders in preparation of other dosage forms is extensive.

may be incorporated into semisolid bases in the preparation of medicated ointments and creams.

Particle Size and Analysis• USP uses descriptive terms to

characterize particle size

-very course -fine

-course -very fine

-moderately course• Sieves- generally made of wire cloth

woven from brass, bronze or other suitable wire

Purpose•obtain quantitative data on the size,

distribution, and shapes of the drug and other components to be used in pharmaceutical formulations

Important factors that a particle size can influence• Drug micronization can increase the rate of

drug dissolution and its bioavailability• Suspendability of particles intended to

remain undissolved but uniformly dispersed in a liquid vehicle

• Uniform distribution of a drug substance in a powder mixture or solid dosage form to ensure dose-to-dose content uniformity

•Penetrability of particles intended to be inhaled for deposition deep in the respiratory tract

•Lack of grittiness of solid particles in dermal ointments, cream, and ophthalmic preparations

Methods for determining particle size• Sieving – passed through a series of sieves

• Microscopy – sized through the use of calibrated grid background

•Sedimentation Rate - measuring the terminal settling velocity through a liquid medium in a gravitational environment - Stoke’s Law

• Light energy diffraction– reduction in lightreaching the sensor as the particle,

dispersed in a liquid or gas, passes through the sensing zone• Laser Holography – pulsed

laser is fired through an aerosolized dimensions with a holographic camera

• Cascade Impaction – separated into various size

ranges by successively increasing the velocity of the airstream in which they are carried

*a reduction in particle size increases the number of particles and the total surface area

Comminution of DrugsSmall Scale:• Trituration – grinding a drug

in a mortar to reduce its particle size • Levigation – preparation of

ointments and suspensions to reduce particle size and grittiness of the added powders

Large Scale:• Mills and Pulverizers – FitzMill –

grinding action of rapidly moving blades, particles are reduced in size and passed through a screen of desired dimension to the collection container

Blending Powders• Spatulation – blending

small amounts of powders by movement of a spatula

• Trituration – may be employed both to comminute and to mix powders

• Geometric Dilution – mixing a small amount of potent substance with a large amount of diluent / ensure the uniform distribution of the potent drug

• Sifting – powders are passed through sifters, resulting in a light and fluffy product•Tumbling – tumbling the powder in a rotating chamber

•Segregation – undesirable separation of the different components of the blend

–Occurs by sifting or percolation, air entrapment (fluidization), particle entrapment (dusting)

–Fine particles tend to sift or percolate through course particles and end up at the bottom of the container and lift the larger particles to the surface

–Dusting occurs when the finer, lighter particles remain suspended in air longer and do not settle as quickly as the larger or denser particles.

Guidelines to minimize/ prevent segregation• Minimum number of transfer steps and

drop heights• Control of dust generation• Control of fluidization of powder• Slow fill/ transfer rate• Appropriate venting

• Use of a deflector, vane or distributor• Proper hopper design and operating valves

Medicated Powders

Can be taken:

1. Internally

2. Externally

INTERNALLY•Taken orally after mixing with water (or in milk formulas in the case of infants)

*reconstitution•Can be inhaled for local or systemic effects

or

EXTERNALLY•Dusted on the affected area from a sifter-type container •Applied from a powder

aerosol•Should bear the label• “EXTERNAL USE

ONLY”

ADVANTAGES

*For patients who have difficulty in swallowing tablets or capsules•Drugs are too bulky to be formed as tablets•May be expected to result in FASTER RATES of dissolution and absorption than solid dos. forms

DISADVANTAGE

*May be undesirable in taste

*Unstable in liquid form (in which case, the manufacturer will

distribute it as dry powders

for constitution; stable for

max of 14 days)

AEROSOL POWDERS

*Powders that are administered by inhalation

*With aid of DRY-POWDER

INHALERS-delivers micronized

particles of medication in

metered quantities

*Most are used in the treatment of asthma and other bronchial disorders

1 to 6 mcm- (in diameter) particle size of micronized medication.

Crystalline alpha-lactose monohydrate

- Pharmaceutical diluent that aids in formulation’s flow properties and protects from humidity.

Powder blowers or insufflators

-may be used to deliver powders to various parts

of body.

BULK AND DIVIDED POWDERS

BULK POWDERS:

a) Antacid

b) Douche powders

c) Med powders for external applic.

d) Brewer’s yeast powders

-limited to nonpotent substances

-stored at room temp in a clean, dry place.

-kept out of reach of children and animals

DIVIDED POWDERS

-for potent substances

-ready to take

-in a variety of small pieces of paper (chartulae)

Commercially available products:

BC powders- for headache

Psyllium mucilloid- laxative

Massengill powder rackets-douche powders

Method of preparation:

*weigh each portion of powder separately before enfolding in a paper

*bock-and-divide method (for nonpotent subs only)

Types of papers used:

a) Vegetable parchment -semi-opaque, moisture resistant.

b) White bond paper- opaque, no resisting properties

c) Glassine-glazed, transparent, moisture resistant

d) waxed- transparent waterproof

Folding of powder paper

Granules•prepared agglomerates of powdered materials• used for the medicinal value of their content• used for pharmaceutical purposes (making tablets, etc.)

Granules•flow well compared to powders•more stable to atmospheric humidity•less likely to cake or harden upon standing

•Irregularly shaped but

may be prepared to be

spherical•Usually in the 4- to 12-mesh sieve size range•Prepared by wet and dry methods

WET METHOD

•May be done in 2 ways:–basic wet method–fluid bed processing (preblending, granulation,

drying)

•Application: drugs which are stable with moisture; for powdered materials which are not compressible

WET METHOD

•Moisten the powder (powder mixture) and then pass the resulting paste through a screen of the mesh size to produce the desired size of granules

WET METHOD

•Granules are placed on drying trays and dried by air or heat.

WET METHOD

•Fluid bed processing – particles placed on a conical piece of equipment, vigorously dispersed and suspended while a liquid excipient is sprayed on the particles and the product dried, forming granules or pellets of defined particle size.

DRY METHOD

•powder mixture is compacted in large pieces & subsequently broken down & sized into granules

•may be done in 2 ways: –roller compactor & granulating machine–Slugging

•Application: heat & moisture- sensitive drugs–ASA, Vit C, Vit B1

DRY METHOD

•Passed through a roll compactor (roll press) –process a fine powder into dense sheets by forcing it through two mechanically rotating metal rolls running counter to each other.

DRY METHOD

•SLUGGING compression of powder into large tablets or “slugs” on a compressing machine under 8,000 to 12,000lb of pressure

DRY METHOD

•Slugs: flat-faced and about 2.5cm(1in.) in diameter •Granulated into the desired particle size, for the production of tablets

DRY METHOD

•Production of fines – powder that has not agglomerated into granules (separated, collected and reprocessed)

EXAMPLES

•Biaxin granules (clarithromycin, oral suspension)•Omnicef (cefdinir, oral suspension)•Augmentin ES-600 (amixicillin/ clavulanate K)•Ceftin (cefuroxime axetil, Oral suspension)

•Lactinex granules (lactobacillus acidophilus, lactobacillus bulgaricus) – treatment of uncomplicated diarrhea and diarrhea due to antibiotic therapy •Zantac EFFERdose tablets – compressed granule effervescent

EFFERVESCENTGRANULATED SALTS•granules of coarse to very coarse powders containing a medicinal agent in a dry mixture composed of

–sodium bicarbonate–citric acid–tartaric acid

•effervescence from the released CO2 masks the undesirable taste of drugs.

EFFERVESCENTGRANULATED SALTS•tartaric acid alone -granules readily lose their firmness & crumble

•citric acid alone - results in a sticky mixture which is difficult to granulate

•prepared by: –dry or fusion method–wet method

Dry or fusion method

•One molecule of water present in each molecule of citric acid acts as the binding agent for the powder mixture

•Granules are dried not exceeding 54C and immediately placed in tight sealed containers

–Acetaminophen for Effervescent Oral Solution USP

WET METHOD

•The source of binding agent is not the water of crystallization from the citric acid but the water added to alcohol as the moistening agent, forming pliable mass for granulation

examples

QUESTIONS