Transcript introduction - Pharmawiki.in

BY
ARJUN NARALA
M.PHARMACY, I SEM
DEPARTMENT OF PHARMACEUTICS
UNIVERSITY COLLEGE OF PHARMACEUTICAL SCIENCES
KAKATIYA UNIVERSITY
WARANGAL.
CONTENTS
Introduction
Defects in Tablets
Defects in sugar coated tablets
Defects in film coated tablets
Conclusion
References
INTRODUCTION
 In the normal process of developing formulations,
and in the routine manufacture of tablets, various
defects are observed. Sometimes, the source of the
problem or the defect is the formulation, the
compression equipment, or a combination of the two.
Some defects are noticed immediately during
manufacturing but others may be noticed during
storage as in the case of capping.
DEFECTS IN TABLETS
 CAPPING AND LAMINATION
 PICKING AND STICKING
 MOTTLING
 DOUBLE IMPRESSIONS
 BLACK SPECKS
 CHIPPING AND SPLITTING
CAPPING AND LAMINATION
 Capping is defined as the partial or complete separation of the
top or bottom crowns of a tablet from the main body of the
tablet.
 Lamination is the separation of a tablet into two or more
distinct layers.
 These processing problems are readily apparent immediately
after compression or may occur hours or even days later.
 Subjecting tablets to the friability test is the quickest way of
revealing such problems.
CAPPING AND LAMINATION
CAUSES AND CORRECTIVE ACTIONS
 Air entrapment
 Reduce press speed
 Precompress granulation
 Reduce quantity of fine particles in the granulation
 Taper dies
 Ensure that punch-to-die clearance is correct
 Excessive pressure
 Reduce tablet weight and/or increase its thickness within
allowable tolerances
 Adjust pressure
CAUSES AND CORRECTIVE ACTIONS
 Too rapid expansion of tablet upon ejection
 Taper dies
 Poor granulation
 Increase quantity of binder; use strong binder
 Excessively dry granulation
 Increase lubricant
 Excessive lubrication of granulation
 Decrease lubricant; blend all ingredients before adding
lubricant
CAUSES AND CORRECTIVE ACTIONS
 Punch cavity too deep
 Use punches with less concave depth
 Punch tips worn
 Refurbish or replace punches
 Lower punch set too low at tablet take-off
 Set lower punch tip flush with top of die
 Tablet take-off bar set too high
 Adjust take-off bar
PICKING AND STICKING
 Picking refers to a tablet material
being removed from the tablets
surface by a punch.
 It is of particular concern when
punch tips have engraving or
embossing.
 Tablet materials adhering to
punches can accumulate to the
point of obliterating the tip
design.
 Sticking refers to a tablet material
adhering to the die wall.
 It results in the buildup of
material on punch faces.
CAUSES AND CORRECTIVE ACTIONS
Excessive moisture
 Check moisture content of granulation; drying
 Check room humidity
 Presence of low-melting-point substances
 Dilution with higher-melting-point materials
 Insufficient compaction force
 Reduce tablet weight and/or increase its thickness within
allowable tolerances
 Inadequate lubrication of granulation
 Check and/or adjust level of lubricant used
CAUSES AND CORRECTIVE ACTIONS
 Punch face condition: pits on punch faces and/or improper draft
on embossing
 Try repolishing punch faces
 Try chrome-plating of punch faces
 Poor embossing design
 Redesign embossing per TSM guidelines, or consult tooling
supplier
MOTTLING
 Unequal distribution of color on a tablet, with light or dark
areas standing out in an otherwise uniform surface.
Causes and corrective actions:
 Drug whose color differs from the tablet excipients or a drug
whose degradation products are colored.
 Use of colorants
 Migration of dyes to the surface of granulation during drying
 Change the solvent system
 Reduce the drying temperature
 Grind to a small particle size
CAUSES AND CORRECTIVE ACTIONS
 High moisture content of granulation
 Dry granulation
 Oversized granulation particles
 Reduce particle size
 Contamination of granulation, usually by grease or oil
 Check oil seals on upper punch guides
 Fit oil/dust caps to upper punches
 Reduce lubrication of upper punches to an acceptable level
 Contamination of granulation from chutes or feed hoppers
 Clean and reset components correctly
DOUBLE IMPRESSION
 This problem is encountered with punches that have a
monogram or other engraving on them.
Causes and corrective actions:
 Rotation of punches
 Adjust antiturning devices
 Use keyed punches
DIRT IN PRODUCT (BLACK SPECKS) :
 Dust,dirt,or press lubrication in the granulation
 Clean press more frequently
 Excessive or wrong press lubrication
 Use proper punch dust caps
 Rubbing of feeder components
CHIPPING OR SPLITTING
 Poor surface finish on punch tips; worn punches and dies
 Poor tooling design (e.g., sharp embossing or bisect lines)
 Polish punch tips; replace punches and dies
DEFECTS IN SUGAR COATED TABLETS
CHIPPING OF COATINGS:
Sugar coatings are inherently brittle and thus prone to chipping if
mishandled.
 Excessive use of insoluble fillers and pigments tends to increase
the brittleness of sugar coatings.
 Avoid them where ever it is possible
 Addition of small quantities of polymers(such as
cellulosics,polyvinylpyrrolidine,acacia,or gelatin) to improve
structural integrity.
CRACKING OF COATINGS:
 Tablet cores that expand, either during or after coating, are
likely to cause the coating to crack.
 Such expansion may result from
1.Moisture absorption by the tablet core.
2.By stress relaxation of the core after compaction.
 Moisture sorption can be minimized by appropriate use of
seal coat.
 Expansion due to post compaction stress relaxation can be
resolved by extending the time between the compaction event
and commencement of sugar coating.
TWINNING (OR BUILD OF MULTIPLES)
 By their very nature, sugar-coating
formulations
are
very
sticky,
particularly as they begin to dry, and
allow adjacent tablets to stick together.
 Build up of multiples really becomes a
problem when the tablets being coated
have flat surface which can easily come
into contact with one another.
 Troublesome with high-dose, capsuleshaped tablets that have high edge
walls.
 Appropriate choice in tablet punch
design can be effectively used to
minimize the problem.
UNEVEN COLOR
 Uneven distribution of color, particularly with the darker
colors, is often visually apparent, and thus a major cause of
batch rejection.
 Poor distribution of coating liquids during application
 Uniform mixing of tablets in the coating process
 Addition of sufficient coating liquids
 Color migration of water-soluble dyes while the coating is
drying
 Change the solvent system
 Reduce the drying temperature
 Grind to a small particle size
 Unevenness of the surface of the subcoat
 Achieve desired surface smoothness
 Washing back of pigment-colored color coatings
 Replace aluminium lakes
 Use combinations of dyes and pigments
 Excessive drying between color applications
 Reduce rate of drying
 Reduce drying temperature
BLOOMING AND SWEATING
 Residual moisture in finished sugar-coated tablets can often
be a problem. over a period of time, this moisture can diffuse
out and affect the quality of the product.
 Moderate levels of moisture egress cause the polish of the
product to take on a fogged appearance, a phenomenon often
termed blooming.
 At higher levels of moisture egress, the moisture may appear
like beads of perspiration on the tablet surface, a phenomenon
often termed sweating.
 Sweating can be much more serious, since tablets stored in
closed containers will ultimately stick together.
 Obtain appropriate levels of moisture.
MARBLING
 To achieve a high-quality, sugar coated product it is important
to ensure that color is uniformly distributed in the color layer,
and at the end of the application of the color coating that a
smooth coating surface is obtained.
 Failure to achieve the requisite smoothness often results in a
marbled appearance on polishing.
 This problem occurs as the result of the collection of wax in the
small surface depressions of a rough coating and is particularly
evident with darker colors.
 Check for smooth surface at the end of color coating.
DEFECTS IN FILM COATED TABLETS
PICKING:
 It results when the coating on two adjacent tablets is not
sufficiently dry before contact between them occurs.
 As the partially dried coating is extremely tacky, once the two
tablets make contact they adhere to one another.
 Once the coating has dried they break apart later under the
influence of attrition.
 In extreme cases the tablets may become permanently glued
together so that twinning occurs.
 Over wetting typically occurs when the spray rate is excessive
for the drying conditions in the process.
 Adjust the spray rate
 Adjust the temperature of drying
 Check for the proper functioning of the spray guns
 Certain types of coating formulations(e.g., those based on
hydroxypropylcellulose, and several of the acrylic aqueous
latex coating systems) are inherently tackier during application.
 Replace with other polymer systems.
ORANGE PEEL(ROUGHNESS)
 Inadequate spreading of the coating
solution before drying causes a bumpy or
orange-peel effect on the coating.
 This indicates that spreading is impeded
by too rapid drying or by high solution
viscosity.
 This is caused by process conditions
which include low spray rates coupled
with excessive drying conditions and use
of excessive atomizing air pressures.
 Adjust the spray rate and drying
conditions
 Coating liquids with high viscosities
 Thinning the coating solution with
additional solvents
In brief optimize the coating process.
EDGE WEAR(CHIPPING)
 Tablet edges are often exposed
to attritional effects, so fracture
at this point results in parts of
the surface being exposed,
referred as chipping.
 Seen with brittle film coatings
that offer insufficient protection
to tablet edges.
 Addition of small quantities of
polymers(such
as
cellulosics,polyvinylpyrrolidine
,acacia,or gelatin) to improve
structural integrity.
FILM CRACKING
 Cracking of film coating occurs when the internal stress
exceeds the tensile strength of the coating.
 The problem is exacerbated when significant differences exist
between the thermal expansion coefficients for the core and
coating.
 Totally unacceptable for products where the applied coating is
a major factor in modifying drug-release characteristics.
 Minimize the internal stresses by adjusting the plasticizer type,
pigment type and their concentration.
 Increase the tensile strength of the film by using high
molecular-weight polymers or polymer blends.
FILM PEELING
 During application of aqueous
coating formulations, cohesive
failure(cracking) of the coating
occurs.
 This coating may peel back from
the surface of the substrate and
result in peeling.
 Cohesive and adhesive failure(
both linked to internal stress)
 Increase the tensile strength of
the film
 Decrease the internal stress
BRIDGING OF LOGOS(INTAGLIATIONS)
 This phenomenon occurs when a
component of the internal stress
becomes sufficiently high so as to
cause partial or complete detachment
of the coating ( from the substrate) in
the region of logo.
 As a result of such detachment, the
film is able to shorten and thus
partially relieve the stress within the
film.
 This defect can be so severe that the
monogram or bisect is completely
obscured.
 Improve film adhesion by adjusting
plasticizer content
 Appropriate design of tablet punches
with respect to logo
IN-FILLING OF LOGOS
 In-filling of logos typically occurs during the spray application
of aerated aqueous film-coating solutions.
 When a foamy coating solution impinges on a regular part of
the tablet surface it will, under the shear forces generated, form
a film with normal characteristics.
 Those droplets of coating liquid that reside in the logo, being
protected from shear forces at the surface, gradually dry to
form a solid foam that eventually obliterates the bisect.
 Judicious monitoring of the fluid application rate and thorough
mixing of the tablets in the pan prevent filling.
BLISTERING
 When coated tablets require further drying in ovens, too rapid
evaporation of the solvent from the core and the effect of high
temperature on the strength, elasticity, and adhesion of the film
may result in blistering.
 Use milder drying conditions.
CONCLUSION
 Tablets are widely used dosage forms but defects in
aesthetic appearance may lead to the rejection of their
administration by the patient.
 From the manufacturer point of view these defects may
lead to reworking or rejection of the batch.
 Although many of these defects may be purely cosmetic
some of them are totally unacceptable.
 So a proper attention by the manufactuer on the source of
defects and their orderly corrections is required.
REFERENCES
 Herbert A. Lieberman, Leon Lachman, Joseph B. Schwartz,
Pharmaceutical dosage forms : Tablets, Second Edition,vol 3.
 Herbert A. Lieberman Leon Lachman, Theory and Practice of
Industrial Pharmacy, 2009.
 James Swarbrick, James C. Boylan, Encyclopedia of
Pharmaceutical technology, Volume 15, 1996.
 James Swarbrick, Encyclopedia of Pharmaceutical technology,
Third Edition, Volume 6, 2007.
 Website:
 www.pharmainfonet.com
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