Transcript Lecture 12. Physical chemical and pharmaceutical

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:
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Easy to handle
Variety of manufacturing methods
Can be mass produced at low cost
Consistent quality and dosing precision
Can be self - administered
Enhanced mechanical, chemical, and
microbiological stability compared to liquid
dosage forms
Tamperproof
Lend themselves to adaptation for other
profiles, e.g., coating for sustained release
Disadvantages of tablets:
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Inability to use unconscious and during
vomiting;
Possibility of tablets cementing in long-term
storage;
Slowly action of medicines substances from
tablets;
Some medicines form concentrated
solutions that irritate the stomach;
Tablets include many auxiliary substances
that are ballast for the human organism.
Classification of the tablets
By the way of obtaining:
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1. Pressed tablets.
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2. Formations or triturations tablets.
By composition:
1.
simple
2.
complex (multicomponent).
By the structure of construction:
1.
Carcass tablets
2.
singlelayer tablets
3.
multilayer tablets
4.
coated tablets
5.
uncoated tablets
Classification by method of
adminietration
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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 :
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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 size
2. Friability of uncoated tablets
3. Resistance to crushing of tablets:
 Hardness or breaking strength
4. Uniformity of dosage units
Uniformity of mass (weight variation)
5. Uniformity of content
6. Dissolution
7. Disintegration
8. Microbiological quality
9. Quantity of active substances
10. 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.
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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:
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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:
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chemical - solubility, reactivity;
Properties of initial substances which are
research to the design and optimization of
solid dosage formulations:
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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:
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structural - mechanical - plasticity, hardness),
elasticity, viscosity of acrystal lattice, etc.
The general design criteria for
tablets are given as follows:
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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 measured
A: 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:
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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 FORMATION
Mixing of the components
(medicines and auxiliary substance)
Wetting of powders mixture with
alcohol or water
Chafing of the mass in the special
plates
Outthrust formed tablets from the
plates
Drying of the tablets
Steps 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 pressing
Methods of tablets production
with compression:
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3.
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Direct compressing.
Pressing the previous granulation.
Granulation Types:
wet granulation;
dry granulation (briquette);
structural granulation;
granulation by melting.
Rotary tabulating machines
(RTM)
Indicators quality of tablets
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Appearance
Disintegration tablets
Solubility
Average mass of tablets and deviation in weight of
separate tablets
Uniformity of content current of substance
Uniformity of mass
Abrasion
Stability to crush
Determination of talc (SiO2)
Quantitative determination of medicinal substances
Identification
Microbiological cleanliness
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