Powders and Granules

Chapter 6:Powders and Granules

Powders

• Describes a formulation in which a drug powder has normally been mixed with otrher powdered excipients to produce the final product.
• The function of added excipients depends upon the intended use of the product.

Granules

• Used as a dosage form, consist of powder particles that have been aggregated to frm a larger particle which usually 2-4 mm in diameter.

POWDERED AND GRANULATED PRODUCTS ARE TRADITIONALLY DISPENSED AS:

• Bulk powders or granules for internal use./
• Divided powders or granules (i.e, single does preparaions) for internal use.
• Dusting powders for external use.

OTHER PREPARTIONS WHICH ARE PRESENTED AS POWDERS OR GRANULES INCLUDE:

• Insufflations for administration to ear, nose and throat.
• Antibiotics to be reconstituted before use
• Powders for reconstitution into injections.
• Dry-powder inhalers.

ADVANTAGES: POWDERED AND GRANULATED PRODUCTS

1. Solid preparations are more chemically stable than liquid ones.

-          Shelf-life of powders for antibiotic syrups, for example, 2-3 years but once they are reconstituted with water, it is 1-2 weeks.

-          Instability observed in liquid preparations is usually the primary reason for presenting some injections as powders to be reconstituted just prior to use.

2. Powders and granules are a convenient form in which to dispense drugs with a large dose.
3. Orally administered powders and granules medicaments have a faster dissolution rate than tablet or capsules, as these must first disintegrate before the drug dissolves.

DISADVANTAGES: POWDERS AND GRANULATED PRODUCTS

• Bulk powders or granules are far less convenient for the patient to carry than a small container of tablets or capsules, and are as convenient as liquid preparation.
• Not well suited for the dispensing of many unpleasant tasting, hygroscopic or deliquescent drugs.
• Bulk powders or granules are not suitable for administering potent drugs with a low dose.
• Powders and granules are not stable method for administration of drugs which are inactivated in or cause damage to the stomach; they should be presented as enteric coated tablets, for example.

MANUFACTURING OF POWDERS

• Small-scale manufacturing - is prepared by one of the following method:

a.     Trituration: the process of reducing substance to fine particles by rubbing them in a mortar and pestle.

b.     Pulverization by intervention – the process of reducing the size of subdivision of solids with the aid of an additional volatile material which can be removed easily after the pulverization has been completed.

Example of this method are:

1.      Pulverization of camphor with the aid of alcohol or other volatile solvents.

2.      Comminution of iodine crystals into the presence of small quantity of ether.

c.     Levigation – the process of first forming a paste by the addition of a suitable solvent to the solid material. Particl siz reduction is then accomplished by rubbing the paste in a mortar with a pestle or on an ointment slab using a spatula.

• Large- scale manufacturing- ameks use of high speed machine for reducing the size of particles or aggregates(e.g, mills), sieves or screens for size classification  and distribution  and mixers which produce a complete blend rapidl with as gentle as possible as mixing action to avoid product damage.

GENERAL TECHNIQUES OF WEIGHING, MEASURING, SIEVING, MIXING. ETC; are applied to both manufacturing and extemporaneous preparation of powders, however, the following procedures shall receive special attention:

1. Use of geometric dilution for the incorporation of small amounts of potent drugs.
2. Reduction of particle size of all ingredients to the same range to prevent stratification of large and small particles.
3. Sieving when necessary to achieve mixing or reduction of agglomerates, especially in preparation of dusting powders into which liquid have been incorporated.
4. Heavy trituration, when applicable, to reduce the bulkiness of the powder.
5. Protection against humidity, air oxidation, and loss of volatile ingredients.

POWDERS ARE MOST COMMONLY PREPARED AS:

1. Divided powders- are dispensed in the form of individual doses an packed in papers, properly folded, pouches made of metal foil, small heat-sealed plastic bags or other container.
2. Bulk powders – are mixed with water or other suitable material prior to administration.

Bulk powders may be classified as:

a.     Oral powders

b.     Dentrifices

c.     Douche powders

d.     Dusting powders

e.     Insufflations

f.        Triturants

GRANULATON

-          The process in which primary powder particles are made to adhere to form larger multi- particle entities called granules.

-          It normally commences after initia dry mixing of the necessary powdered ingredients so that a uniform distribution of each ingredients throughout the mix is achieved.

-          After granulation, granules will either be packed or they may be mixed with other excipients prior to tablet compaction or capsule filling.

REASONS FOR GRANULATION

• To prevent segregation of the constituents of the powder mix.
• To improve the low properties of the mix.
• T improve the compaction characteristic f the mix.

METHODS OF GRANULATION

In a suitable formulation, different excipients will be needed in addition to the drug.

-          Diluents- to produce a unit dose weith of suitable size.

-          Disintegrating agents – aid break-up of the granule when when it reaches a liquid medium.

-          Adhesives(dry powder form) – if dry granulation is employed.

1. Dry granulation – particles are aggregated at high pressure; for drugs that do not compress well after wet granulation or those that are sensitive to moisture.

a.     Slugging method

-          Slugging the powders (formation of a large tablet called a slug)

-          Slugs are granulated using an appropriate equipment

-          Sieve the granules to obtain desired size.

b.     Roll- compaction method

-          Powders are rolled into dense sheets

-          Sheets are granulated using a mechanical granulator

-          Sieve granules to obtain desired size

2. Wet-granulation- involves the massing of a mix of dry primary powder particles using a granulating fluid.

~Granulating fluid – containing a solvent that must be volatile and nontoxic.

~Typical liquid – water

~granulation liquid may be used alone or more, usually as a solvent containing a dissolved adhesive to ensure particle adhesion once granule is dry.

~water is commonly used.

~ The wet mass is forced through a sieve to produce wet granules of desired size which are then dried.

~ ADVANTAGE: non-flammable

~DISADVANTAGE: may adversely affect any stability and needs a longer drying time than organic solvents.

 

WET GRANULATORS:

1.      Smear granulators

2.      High speed mixer/ granulator

3.      Fluidized- bed granulators.