PowdersAseel Samaro

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

Definition !?

The term ‘Powder’ may be used to describe:

The physical form of a material, that is, a dry substance composed of finely divided particles.

Or, it may be used to describe a type of pharmaceutical preparation, that is, a medicated powder intended for:

internal (i.e., oral powder)external (i.e., topical powder) use.

Topical Powder Oral Powder

Although the use of medicated powders in therapeutics is limited, the use of powdered substances in the preparation of other dosage forms is extensive.

For example:1. Powdered drugs may be blended with powdered fillers and other

pharmaceutical ingredients to fabricate solid dosage forms as tablets and capsules

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

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

Advantages Disadvantages- More stable than liquid

- More convenient to swallow than tablet or capsules

- Used in blending with medicated application as ointments, suppositories and pastes

- Can be prepared into granules for use in preparing tablets and or reconstituted to liquid form

- Rapid therapeutic effect due to large surface area

- Useful for bulky drugs with large dose

- Unpleasant tasting of drugs

- It is difficult to protect powders containing hygroscopic, deliquescent (tending to melt or dissolve in humid environment), or aromatic materials from decomposition.

- Time and expenses require in the preparation of uniform powders are great

- Patient may misunderstand the correct method of use. Without clear instruction, patients may inhale through the nose a drug intended for oral administration.

Before their use in the preparation of pharmaceutical products, solid materials first are characterized to determine their chemical and physical features, including:

MorphologyPuritySolubilityFlowabilityStabilityparticle sizeUniformityCompatibility

The particles of pharmaceutical powders and granules may range from being extremely coarse, about 10 mm (1 cm) in diameter, to extremely fine, approaching colloidal dimensions of 1 μm or less.

In order to characterize the particle size of a given powder, the United States Pharmacopeia (USP) uses these descriptive terms:

1. very coarse2. Coarse3. moderately coarse4. Fine5. very fine

These terms are related to the proportion of powder that is capable of passing through the openings of standard sieves of varying fineness in a specified period while being shaken, generally in a mechanical sieve shaker

PARTICLE SIZE AND ANALYSIS

This figure represents the standard sieve numbers and the openings in each, expressed in millimeters and in microns.

o Very coarse (No. 8): All particles pass through a No. 8 sieve and not more than 20% pass through a No. 60 sieve.

o Coarse (No. 20): All particles pass through a No. 20 sieve and not more than 40% pass through a No. 60 sieve.

oModerately coarse (No. 40): All particles pass through a No. 40 sieve and not more than 40% pass through a No. 80 sieve.

o Fine (No. 60): All particles pass through a No. 60 sieve and not more than 40% pass through a No. 100 sieve.

o Very fine (No. 80): All particles pass through a No. 80 sieve. There is no limit to greater fineness.

Powders of vegetable and animal origin drugs are officially defined as follows

Granules typically fall within the range of 4- to12-sieve size, although granulations of powders prepared in the 12- to 20-sieve range are sometimes used in tablet making.

The purpose of particle size analysis in pharmacy is to obtain quantitative data on The sizeDistributionShapes of the drug and other components to be used in pharmaceutical

formulations.

There may be substantial differences in particle size, crystal morphology, and amorphous character within and between substances.

1. Dissolution rate of particles intended to dissolve; drug micronization can increase the rate of drug dissolution and its bioavailability

2. Suspendability of particles intended to remain undissolved but uniformly dispersed in a liquid vehicle (e.g., fine dispersions have particles approximately 0.5 to 10 μm)

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

4. Penetrability of particles intended to be inhaled for deposition deep in the respiratory tract (e.g., 1 to 5 μm)

5. Lack of grittiness of solid particles in dermal ointments, creams, and ophthalmic preparations (e.g., fine powders may be 50 to 100 μm in size)

Particle size can influence a variety of important factors, including the following:

Average particle size (mean) Particle size distribution

Parameters important in particle size determination

Sieving, in which particles are passed by mechanical shaking through a series of sieves of known and successively smaller size and the proportion of powder passing through or being withheld on each sieve is determined (range about 40 to 9,500 μm, depending upon sieve sizes)

A number of methods exist for the determination of particle size

Analytical sieving Sampling process

In order to obtain a powder sample, which represent the whole batch, we proceed as in the following manner

Use a powder sampler (thief)

What is the importance of obtaining an optimum quantity of powder for sieve analysis?

Because an excessive quantity of powder1. Could deform the mesh of the sieve2. Does not permit a regular flowing of the powder over the mesh of

the sieve So a wrong classification will be obtained

The sieving process should be carried out automatically to be reproducible

With automatic sieving (6-8 sieves placed one over the other from the higher to the lower sieve)

Put a powder sample of 100 g in the upper sieve, close with its cover

Shake for 5 min

Normally the process can be stopped if within 1 minute no more than 0.1% of the powder passes

At the end of the process the powder sample will be distributed between the sieves according to their diameter

SEDIMENTATION RATE, in which particles is determined by measuring the terminal settling velocity of particles through a liquid medium in gravitational or centrifugal environment (range: 0.8-300 micrometers)

Sedimentation rate may be calculated from Stokes’ law.

The sedimentation process is under the control of Stock’s law:

r is the radius of the sphere that has a volume equal to the particle. is the particle density. o is the density of the dispersion medium or vehicle. is the vehicle viscosity. g is the gravity acceleration.

9)(2 0

2

grV

May 1, 2023 21

This equipment counts the particles & classifies them in different dimensional classes

It permits to measure the volume of the particles using the conductometric method

Counter coulter

Microscopy – particles are sized through the use of calibrated grid background or other measuring device ( range 0.2 to 100 micrometers)

Flow of powder

Factors that decrease the flow of powder:1. Superficial adhesiveness2. Shape of the particles: Spherical particles flow quickly while irregular

shaped particles flow slowly3. Surface of the particles: Wrinkled surface has low flowability while

smooth surface have high flowability4. The presence of electrostatic charges on the surface of the particles5. The hygroscopicity of the powders

Important magnitude in powder technology

Disadvantages of a bad powder flow:An incomplete & irregular filling of dies or bottles is achieved

Advantages of good powder flow Filling the dies in very short time This means complete and regular filling of dies or bottles

Flow enhancers improve the flowability of the powder by reducing interparticle friction

Excipients that have anti-adherent or lubricant properties may enhance powder flowability

Usually glidants are hydrophobic types substance1. Talc2. Mg stearate3. Starch4. Silica gel

Flow enhancer or Glidants

If bad flowability is due to:The humidityHygroscopicity The use of MgO & SiO2 is advisable

Lipophilic glidants decreaseDisintegration of tabletsDissolution of the active material Thus, minimum quantity of glidant should be used

The angle of repose is a relatively simple technique for estimating the flow properties of a powder.

It can easily be determined by allowing a powder to flow through a funnel and fall freely onto a surface.

The height and diameter of the resulting cone are measured and the angle of repose is calculated from this equation:

tan q = h/r

Angle of repose

θ = tan-1(h/r) where

h = height of pile r = radius of the base of the pile

Excellent flowability if θ < 25o

Good flowability if 25o < θ < 30o

Passable flowability if 30o < θ < 40o

Very poor flowability if θ > 40o

h

r

Types of Volume: True volume (VT) Bulk volume (VB) Relative volume (VR)

VR = VB / VT

VR tends to become unity as all air is eliminated from the mass during the compression process.

Mass-Volume relationships

• True density (ρT = M / VT ) • Bulk density (apparent) (ρa = M / VB)• Relative density (ρR = M / VR)

ρR = ρB / ρT

Types of Density: M is the mass of powder

Porosity = (V bulk – V / V bulk) * 100

Porosity (ε ):

The bulk density of a powder is the ratio of the mass of an untapped powder sample and its volume including the contribution of the interparticulate void volume. The bulk density is expressed in grams per milliliter (g/mL)

The tapped density is obtained by mechanically tapping a graduated measuring cylinder or vessel containing the powder sample.

USP

Tapped density = M / Tapped V

The process of reducing the particle size of a solid substance

Objectives of Comminution• Facilitate crude drug extraction• Increase the dissolution rates of drugs• Aid in the formulation process• Enhance absorption

COMMINUTION OF DRUGS

On a small scale, the pharmacist reduces the size of chemical substances by grinding with a mortar and pestle.

A finer grinding action is accomplished by using a mortar with a rough surface (as a porcelain mortar) than one with a smooth surface (as a glass mortar).

Grinding a drug in a mortar to reduce its particle size is termed trituration or comminution.

COMMINUTION OF DRUGS

Trituration Levigation (to make smooth)

On a large scale, various types of mills and pulverizers may be used to reduce particle size.

The following figure shows one such piece of equipment, a FitzMill comminuting machine with a product containment system.

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

The collection and containment system:oprotects the environment from chemical dusto reduces product lossoprevents product contamination.

Levigation is commonly used in small-scale preparation of ointments and suspensions to reduce the particle size and grittiness of the added powders.

A mortar and pestle or an ointment tile may be used.

A paste is formed by combining the powder and a small amount of liquid (the levigating agent) in which the powder is insoluble.

The paste is then triturated, reducing the particle size.

The levigated paste may then be added to the ointment base and the mixture made uniform and smooth by rubbing them together with a spatula on the ointment tile.

Mineral oil and glycerin are commonly used levigating agents.

Levigation

When two or more powdered substances are to be combined to form a uniform mixture, it is best to reduce the particle size of each powder individually before weighing and blending.

Depending on the nature of the ingredients, the amount of powder, and the equipment, powders may be blended by spatulation, trituration, sifting, and tumbling.

BLENDING POWDERS

Spatulation is blending small amounts of powders by movement of a spatula through them on a sheet of paper or an ointment tile.

It is not suitable for large quantities of powders or for powders containing potent substances, because homogeneous blending is not as certain as other methods.

• Spatulation

Trituration may be employed both to comminute and to mix powders. If simple admixture is desired without the special need for comminution, the glass mortar is usually preferred.

• Trituration

When a small amount of a potent substance is to be mixed with a large amount of diluent, the geometric dilution method is used to ensure the uniform distribution of the potent drug.

This method is especially indicated when the potent substance and other ingredients are the same color and a visible sign of mixing is lacking.

By this method, the potent drug is placed with an approximately equal volume of the diluent in a mortar and is mixed thoroughly by trituration.

Then, a second portion of diluent equal in volume to the mixture is added and the trituration repeated

This process is continued by adding an equal volume of diluent to the powder mixture and repeating this until all of the diluent is incorporated.

Some pharmacists add an inert colored powder to the diluent before mixing to permit visual inspection of the mixing process.

Powders may also be mixed by passing them through sifters like those used in the kitchen to sift flour.

Sifting results in a light, fluffy product.

This process is not acceptable for the incorporation of potent drugs into a diluent powder.

• Sifting

Another method of mixing powders is tumbling the powder in a rotating chamber.

Special small-scale and large-scale motorized powder blenders mix powders by tumbling them.

Mixing by this process is thorough but time consuming.

Such blenders are widely employed in industry, as are mixers that use motorized blades to blend powders in a large vessel.

• Tumbling

TUMBLERS

V Type Pharmaceutical Mixer

Double Cone Tumbling Mixer

Planetary Mixers

Size Shape Density Electrostatic Forces Limits of Blend Segregation Mechanisms

Factors in Blending

PHAR 332 Birzeit Un. Dr Hani Shtaya

Segregation is an undesirable separation of the different components of the blend.

Segregation may occur by sifting or percolation, air entrapment (fluidization), and particle entrapment (dusting).

Fine particles tend to sift or percolate through coarse particles and end up at the bottom of the container and actually “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.

Segregation

Segregation can take place whenever forces are applied to the powder, for example, by way of gravity, vibration, or air flow.

These forces act differently on particles with different physical characteristics, such as particle size, shape, and density.

Most commonly, particles separate as a result of particle size differences.

Some medicated powders are intended to be used internally and others, externally.

Most powders for internal use are taken orally after mixing with water or in the case of infants in their infant formulas.

Some powders are intended to be inhaled for local and systemic effects.

Other dry powders are commercially packaged for constitution with a liquid solvent or vehicle, some for administration orally, others for use as an injection, and still others for use as a vaginal douche.

Medicated powders for external use are dusted on the affected area from a sifter-type container or applied from a powder aerosol.

Powders intended for external use should bear a label marked external use only or a similar label.

MEDICATED POWDERS

Medicated powders for oral use may be intended for:local effects (e.g., laxatives) or systemic effects (e.g., analgesics)And may be preferred to counterpart tablets and capsules by patients who

have difficulty swallowing solid dosage forms.

The doses of some drugs are too bulky to be formed into tablets or capsules of convenient size, so they may be administered as powders.

For administration, they can be mixed with a liquid or soft food.

Powders taken orally for systemic use may be expected to result in faster rates of dissolution and absorption than solid dosage forms, because there is immediate contact with the gastric fluids.

A primary disadvantage of the use of oral powders is the undesirable taste of the drug.

Some medications, notably antibiotics for children, are intended for oral administration as liquids but are relatively unstable in liquid form.

They are provided to the pharmacist by the manufacturer as a dry powder or granule for constitution with a specified quantity of purified water at the time of dispensing.

Under labeled conditions of storage, the resultant product remains stable for the prescribed period of use, generally up to 2 weeks.

Some medicated powders are administered by inhalation with the aid of dry-powder inhalers, which deliver micronized particles of medication in metered quantities.

AEROSOL POWDERS

Most of these products are used in the treatment of asthma and other bronchial disorders that require distribution of medication deep in the lungs.

To accomplish this, the particle size of the micronized medication is prepared in the range of 1 to 6 μm in diameter.

In addition to the therapeutic agent, these products contain inert propellants and pharmaceutical diluents, such as crystalline alpha-lactose monohydrate, to aid the formulation’s flow properties and metering uniformity and to protect the powder from humidity.

Powder blowers or insufflators may be used to deliver dry powders to various parts of the body, e.g., nose, throat, lung, vagina. Depression of the device’s rubber bulb causes turbulence of the powder in the vessel, forcing it out through the orifice in the tip.

Medicated powders may be provided to the patient in bulk or may be divided into unit of- use packages.

Some powders are packaged by manufacturers, whereas others are prepared and packaged by the pharmacist.

BULK AND DIVIDED POWDERS

Among the bulk powders available in prepackaged amounts are:

a. Antacids (e.g., sodium bicarbonate) and laxatives (e.g., psyllium [Metamucil]), which the patient takes by mixing with water or another beverages before swallowing

b. Douche powders: dissolved in warm water by the patient for vaginal use

c. Medicated powders for external application to the skin, usually topical antiinfectives (e.g., bacitracin zinc and polymyxin B sulfate) or antifungals (e.g., tolnaftate)

d. Brewer’s yeast powder containing B-complex vitamins and other nutritional supplements.

In some cases, a small measuring scoop, spoon, or other device is dispensed with the powder for measuring the dose of the drug.

• Bulk Powders

Dispensing powder medication in bulk quantities is limited to nonpotent substances.

Powders containing substances that should be administered in controlled dosage are supplied to the patient in divided amounts in folded papers or packets.

Patients should be educated about appropriate handling, storage, measurement, and preparation of bulk powder prescription and nonprescription products in addition to the customary counseling at the time of dispensing or purchase.

Generally, these products are stored at room temperature in a clean, dry place.

These products should be kept out of the reach of children and animals.

Patients should be instructed how to measure the appropriate amount of the powder and be told the type of liquid or vehicle to use to deliver the medication consistent with package and/or physician instructions.

After a powder has been properly blended (using the geometric dilution method for potent substances), it may be divided into individual dosing units based on the amount to be taken or used at a single time.

Each divided portion of powder may be placed on a small piece of paper that is folded to enclose the medication.

A number of commercially prepared premeasured products are available in folded papers or packets, including:

headache powders powdered laxatives (e.g., psyllium mucilloid, cholestyramine resin)douche powders (e.g., Massengill powder packets)

• Divided Powders

Divided powders may be prepared by the pharmacist as follows.

Depending on the potency of the drug substance, the pharmacist decides whether to weigh each portion of powder separately before enfolding in a paper or to approximate each portion by using the block and- divide method.

By the latter method, used only for non-potent drugs, the pharmacist places the entire amount of the prepared powder on a flat surface such as a porcelain or glass plate, pill tile, or large sheet of paper and, with a large spatula, forms a rectangular or square block of the powder having a uniform depth.

Then, using the spatula, the pharmacist cuts into the powder lengthwise and crosswise to delineate the appropriate number of smaller, uniform blocks, each representing a dose or unit of medication.

Each of the smaller blocks is separated from the main block with the spatula, transferred to a powder paper, and wrapped.

The selection of the type of paper is based primarily on the nature of the powder.

If the powder contains hygroscopic materials, waterproof or waxed paper should be used.

Powders containing volatile components should be wrapped in waxed or glassine papers.

Powders containing neither volatile components nor ingredients adversely affected by air or moisture are usually wrapped in a white bond paper

Disadvantages Of Divided Powders1. Difficult to protect from atmospheric moisture or oxygen2. Not well suited for dispensing of many unpleasant tasting hygroscopic

drug3. Preparation is time-consuming, therefore more costly.

Advantages Of Divided Powders4. Flexibility5. Dissolve more rapidly then compressed solid dosage form6. Rapid therapeutic effect7. StabilityEase of administration

Problems encountered in powder formulation1- Hygroscopic and Deliquescent Powder

Problem: Absorption of moisture from air leading to partial or complete liquefaction.Solution:

a. Reduce the amount of surface area exposed to the moistureb. Packed in aluminum foil or in plastic film packetsc. Addition of light magnesium oxide to reduce the tendency to dampd. Addition of adsorbent materials such as starch

Examples: Ammonium Bromide/Chloride/Iodide, Calcium Bromide/Chloride, Ephedrine SulfateHyoscyamine HBr/Sulfate, Lithium Bromide, Phenobarbital Sodium, Potassium Acetate/Citrate

Check Table 6.3

2- Efflorescent powders

(is the loss of water (or a solvent) of crystallization from a hydrated or solvated salt to the atmosphere on exposure to air.)

Problem: Crystalline substances which during storage loose their water of crystallization and change to powder (to be efflorescent). The liberated water convert the powder to a paste or to a liquid.

Examples: Alum- atropine sulfate- citric acid- codeine phosphate…

Solution: Using the anhydrous form + treating it in a manner similar to hygroscopic powders ( include drying bulky powder)

3- Eutectic Mixtures

A proportion of components that will give the lowest melting point

Problem: mixture of substances that liquefy when mixed, rubbed or triturated together. The melting points of many eutectic mixtures are below room temperature.

Examples: menthol- thymol- phenol- salol- camphor…….

Solution: A- using inert adsorbent such as starch, talc, lactose to prevent dampness of the powderB- dispensing the components of the eutectic mixture separately.

4- Explosive mixtures

Oxidising agents give oxygen to another substance.Reducing agents remove oxygen from another substance.

Problem: Oxidizing agents (ex. Pot. Salts of chlorate, dichromate, permanganate and nitrate- Sod. Peroxide- silver nitrate and silver oxide) explore violently when triturated in a mortar with a reducing agent ( ex. sulfides- sulfur- tannic acid- charcoal).

Solution: A- Comminute each salt separately. B- Subject to a minimum pressure.