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2 CONTENTS  Introduction  Defects in Tablets  Defects in sugar coated tablets  Defects in film coated tablets  Conclusion  References

3 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.


5 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.


7 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

8 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

9 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

10 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.

11 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

12 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

13 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

14 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

15 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

16 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

17 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

18 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.

19 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.

20 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, capsule- shaped tablets that have high edge walls.  Appropriate choice in tablet punch design can be effectively used to minimize the problem.

21 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

22  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

23 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.

24 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.

25 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.

26 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.

27 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.

28 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.

29 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.

30 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

31 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

32 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.

33 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.

34 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.

35 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, James Swarbrick, James C. Boylan, Encyclopedia of Pharmaceutical technology, Volume 15, James Swarbrick, Encyclopedia of Pharmaceutical technology, Third Edition, Volume 6,  Website:



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