Physical chemical and pharmaceutical-technological

properties of powder and granules and their impact on the technology of

solid dosage forms. Tablets.

Tablets are solid preparations each containing a single dose of one or more active substances.

They are obtained by compressing uniform volumes of particles or by another suitable manufacturing technique, such as extrusion, moulding or freeze-drying (lyophilisation).

Advantages of tablets: 1. Easy to handle

2. Variety of manufacturing methods

3. Can be mass produced at low cost

4. Consistent quality and dosing precision

5. Can be self - administered

6. Enhanced mechanical, chemical, and microbiological stability compared to liquid dosage forms

7. Tamperproof

8. Lend themselves to adaptation for other profiles, e.g., coating for sustained release

Disadvantages of tablets:

1. Inability to use unconscious and during vomiting;

2. Possibility of tablets cementing in long-term storage;

3. Slowly action of medicines substances from tablets;

4. Some medicines form concentrated solutions that irritate the stomach;

5. Tablets include many auxiliary substances that are ballast for the human organism.

Classification of the tablets By the way of obtaining: 1. Pressed tablets. 2. Formations or triturations tablets. By composition: 1. simple2. complex (multicomponent). By the structure of construction: 1. Carcass tablets2. singlelayer tablets3. multilayer tablets4. coated tablets5. uncoated tablets

Classification by method of adminietration Oriblettae - tablets, for oral adminietration Resoriblettae - tablets, sublingual use Implantabulettae - made aseptic, are used as implants Injectabulettae - made aseptic, are used to obtain of

injection solutions Solublettae - used for preparing solutions with different

pharmaceutical purposes Dulciblettae - sweet tablets for chew Uretratoria - urethral tablets vagitoria, bacilli, boli, - pressed vaginal and rectal

dosage forms

Several categories of tablets for oral use :

uncoated tablets; coated tablets; effervescent tablets; soluble tablets; dispersible tablets; orodispersible tablets; gastro-resistant tablets; modified-release tablets; tablets for use in the mouth; oral lyophilisates.

Tablet characterization

1. Appearances: Tablet thickness Tablet shape and size2. Friability of uncoated tablets 3. Resistance to crushing of tablets: Hardness or breaking strength4. Uniformity of dosage unitsUniformity of mass (weight variation)5. Uniformity of content6. Dissolution7. Disintegration8. Microbiological quality9. Quantity of active substances10. Identification of active substances

Tablets need to be hard enough that they don't break up in the bottle, yet friable enough that they disintegrate in the gastric tract.

Tablets need to be strong enough to resist the stresses of packaging, shipping and handling by the pharmacist and patient.

Most drug and inactive excipients used in tablet formulation are in the solid state as amorphous powder or crystals of various morphological structures.

There may be substantial differences in particle size, surface area, crystal morphology, wetting, and flowability as well as many physical properties of drug, excipients, and their blends.

In tablet design many factors have to be taken into account, such as the physicolchemical properties of active compound and excipients.

An important role also has to be attributed to tableting machines.

Properties of initial substances which are research to the design and optimization of solid dosage formulations:

physical - true density; shape, size and surface characteristics of particles, specific surface, adhesive forces (sticking onto a surface) an' cohesion (slicking of particles inside a body), interfacial activity, melting point, etc.;

Properties of initial substances which are research to the design and optimization of solid dosage formulations:

chemical - solubility, reactivity;

Properties of initial substances which are research to the design and optimization of solid dosage formulations:

technological - loose density, tapped density, compaction degree, flowabitity moisture content, particle size distribution, dispersity, porosity» compressibility

Properties of initial substances which are research to the design and optimization of solid dosage formulations:

structural - mechanical - plasticity, hardness), elasticity, viscosity of acrystal lattice, etc.

The general design criteria for tablets are given as follows: Optimal drug dissolution and, hence, availability from the

dosage form for absorption consistent with intended use; Accuracy and uniformity of drug content. Stability, including the stability of the drug substance, the

overall tablet formulation, disintegration, and the rate and extent of drug dissolution from the tablet for an extended period.

Patient acceptability. As much as possible, the finished product should have an attractive appearance, including color, size, taste, etc., as applicable, in order to maximize patent acceptability and encourage compliance with the prescribed dosing regimen.

Manufacturability. The formulation design should allow for the efficient, cost-effective, practical production of the required batches.

Ways of obtaining Tablets

Formation Compression

All tablets are made by a process of compression. Compressing powder or granule into a tablet is one of the simplest and oldest ways of forming a product known to humans.The basic unit of any tablet press is tooling consisting of

two punches and a die,called a station. The upper and lower punches come together in the die that contains the tablet formulation. Solid, in the form of relatively small particles, is contained in a die and a compressing force of several tonnes is applied to it by means of punches.

Filling: The volume of the powder is measuredA: The lower punch is allowed to descend to its lowest point.B: The bore of the die is fi lled completely with powder.C: The lower punch is raised to a predetermined point so that excess.D: The powder is leveled by passing under a blade.E: This ensures that the bore of the die is filled with as exact volume of the material to be used, and the next stage can begin.

Compression: Pressure is applied to form the granule into a solid F: The upper punch is lowered into the bore of the die.G: Precompression gives the powder an initial “ punch ” to remove excess air.H: The powder is fully compressed.I: The correct pressure is reached.J: The upper punch is lifted out of the way ready for tablet ejection.

Ejection The tablet is ejected and the next tablet will be formed K: The lower punch begins to rise in the bore of the die lifting the tablet until step L is reached.L: Its base is level with the tap of the die.M: The tablet is pushed aside into the take - off chute by passing under a static blade.N: The lower punch moves to its lowest position ready for filling similar to A and the entire cycle is repeated.

Properties for successfully transformatio of the powder into

tablets:1. Good particle flow.2. The ability of the particles to cohere

under the influence of a compressing force. This coherence must be retained after the compressing force has been removed.

3. The ability of the tablet to be ejected from the die after the compressing force has been removed.

Excipient materials are normally required alongwith the active ingredient in order to give the tablet the desired properties.

Fillers Binder Disintegrating Agent Glidant, Antiadherent, and Lubricant Flavor, Sweetener, and Colorant

Types of disintegrants (acting with different mechanisms):

1. promotion of the uptake of aqueous liquids by capillary forces,

2. swelling in contact with water, 3. release of gases when in contact with

water, 4. destruction of the binder by

enzymatic action.

Ways of obtaining Tablets

Formation Compression

Formation used for: Formation used for:

► triturations tablets ► tablets for obtaining solutions, drops ► substances exploding under action

pressure (nitroglycerin) ► when not need great strength of

tablets ► when not appropriate introduce

great number of auxiliary substances in the tablet

STAGES OF FORMATIONSTAGES OF FORMATIONMixing of the components

(medicines and auxiliary substance)Mixing of the components

(medicines and auxiliary substance)

Wetting of powders mixture with alcohol or water

Wetting of powders mixture with alcohol or water

Chafing of the mass in the special plates

Chafing of the mass in the special plates

Outthrust formed tablets from the plates

Outthrust formed tablets from the plates

Drying of the tabletsDrying of the tablets

Steps of the compression processSteps of the compression process

1. The filling exact volume of the material from funnel in the channel of the die;

2. Pressure is applied to form the powder into a solid;

3. Outthrust tablets from the matrix by raising the lower punch.

Steps of the process of pressingSteps of the process of pressing

Methods of tablets production Methods of tablets production with compression: with compression:

1. Direct compressing.

2. Pressing the previous granulation.

3. Granulation Types: wet granulation; dry granulation (briquette); structural granulation; granulation by melting.

Rotary tabulating machines (RTM)

Indicators quality of Indicators quality of tablets tablets

1. Appearance2. Disintegration tablets3. Solubility 4. Average mass of tablets and deviation in weight of

separate tablets 5. Uniformity of content current of substance 6. Uniformity of mass 7. Abrasion 8. Stability to crush 9. Determination of talc (SiO2)10. Quantitative determination of medicinal substances 11. Identification 12. Microbiological cleanliness

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