Solid Dosage Forms (powder & granules)

Examples of solid dosage forms

Powders, granules, capsules, tablets

Pros of tablets and capsules

Elegant, precise, storage, stability

Pros of powder

Manufacturing, storage, stability, dose adjustment

Pros of solutions

Dosage adjustments, storage

Pros of suspension

Storage, dosage adjustments

Examples of kinds of excipients

Diluent

Filler

Binder/Adhesive

Disintegrant

Lubricant

Flavoring System

Colorant

Coating System

What are powders

The physical form of finely divided solids. Can be medicated powders or inhaled. They are extensively used in other dosage forms.

What dosage forms use powders

Tablets, capsules, solutions, suspensions, semisolids

Physiochemical properties of powders

Particle size and distribution

Morphology (amorphous or crystalline)

purity

solubility

stability

uniformity

compatibility with any other formulation components

Micrometrics

The science of small particles. It studies a number of characteristics including particle size, particle distribution, shape, angle of repose, porosity, true volume, bulk volume, apparent density, true density, bulkiness

Particle Size and Distribution

Particles in pharmaceutical powders vary from extremely coarse (10mm) to extremely fine (1 micrometer). The terms related to portion of powder capable of passing sieves of varying fineness in a specified period of time while shaking.

Terms to define coarsness

Very coarse

Coarse

Moderately Coarse

Fine

Very Fine

Dissolution rate of particles

Particle Size/Micronization of drug can increase the rate of drug dissolution and bioavailability

Dose to Dose content uniformity

Particle size can influence uniformity. Smaller particles separate from smaller ones and in suspensions sedimentation rate is faster with large particles

Deposition and penetration of particles

Particle size can limit deposition/penetration. 1-5 micrometers is best.

Lack of grittiness

Important in ointments, creams, and ophthalmic solution

Sieving

Particles are passed through series of sieves of successive smaller size, in order to determine the percentage of passing through or being withheld on each sieve. Used to obtain information on particle size, distribution, and shape.

Microscopy

Particles are sized using a calibrated grid background range 0.2-100 micrometers

Sedimentation rate

Size is determined by measuring the settling velocity of particles through a liquid medium in gravitational or centrifugal environment using stokes equation. Range 0.8-300 micrometers.

Powder Flow

Important factors in processing and manufacturing of dosage forms. Flow affects filling uniformity of powders, tablets, and capsules. It also affects the transfer rates of powders in plants.

Particle Size Flow Rates

250-2000 microm - flow freely

75-250 microm - may cause problems

<100 microm - flow is a problem

Angle of Repose

It is used to estimate the flow properties of powders by allowing a powder to flow through a funnel and fall freely onto a surface. Powders with a low angle of repose flow freely while powders with a high angle of repose flow poorly.

Equation for Angle of Repose

tan sigma = h/r

h is height of powder cone

r is the radius of the powder cone

How can spheres pack together

In cube or in triangle

If the particles are not uniform, smaller ones will go into the spaces between the bigger ones and decrease the void area. Packing and flow affect filling, container size, and ease of working with the powders

Porosity

Represents the void between particles

Bulk volume

The volume occupied by a unit weight (Vbulk)

True Volume

The volume occupied by a unit weight without the volume of the spaces between the particles (V)

Void ratio equation

(V bulk - V) / V bulk

Porosity equation

Void ratio x 100

Bulk volume equation

true volume + porosity

Apparent density equation (Pa)

(weight of sample)/V bulk

True density equation (p)

Weight of sample / V

Bulkiness equation (B)

1/Pa

Tapped density equation

Weight / V after tapping

Comminution of Drugs

On a small scale the pharmacist reduces the size of substances by grinding with a mortar and pestle (trituration)

On a large scale, various types of mills with screens may be used which are connected to a containment system in order to protect the environment from chemical dust, reduce product loss, and prevent product contamination

Methods of Blending powders

Spatulation and Trituration

Spatulation

Blending of small amounts of powders by movement of a spatula through them on a sheet of paper or an ointment tile

Trituration

Comminution and mixing, used when a small amount of a potent substance is to be mixed with a large amount of diluent in a mortar and pistole

Geometric Dilution method

Is used to ensure uniform distribution and to ensure uniform mixing.

Ex: tumbling in a rotating chamber (V-mixer, conical mixer)

Medicated powders

Are used internally and externally. Most powders for internal use are taken orally after mixing with water. Some powders are intended to be inhaled for local or systemic effects. Other dry powders are package with a solvent, some for oral administration other for use as an injection. Medicated powder for external use are dusted on the affected area from a sifter type container.

How may powders be provided to patients

As bulk powders: several doses packaging in a container. Usually non-potent drugs like sodium bicarb, metamucil.

As Divided powders: by pharmacist or manufacturer in individual doses (sachets, folded paper)

Benefits of medicated powders

Preferred by patient having difficulty swallowing tablets or capsules. Preferred when the dose is too big to be formulated into a tablet or capsule. Faster dissolution rate compared with other solids. Dose adjustment is easier than tablets.

Granules

Prepared agglomerates of smaller particles of powder. Irregular in shape of spherical.

Benefits of granules

When compared to initial powders granules have better flow, compressibility, stability, wettability. Granulation also help maintain homogeneity

Granule Preparation Methods

Dry method

Wet method

Dry method

Uses cohesive binders and machines.

Method 1 Roller Compaction: Powder mixture is forced between two counter-rotating roller to form sheets. The sheets are broken down into granules.

Method 2 Slugging: Powder mixture is compressed into large tablets. The tablets are then broken down into granules.

Wet method

Binding powders with adhesive liquid in a process called kneading or wet massing

Sieving or sizing the wet granules

Drying the sized wet granules

Sieving to attain the required size

Examples of Commercial Powders/Granules

Advair Diskus, Miralax, Cholestyramine oral susp, Biaxin