Tablets manufacturing defects DMS 2012-13

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TABLETS MANUFACTURING DEFECTS CAUSES AND REMEDIES THEREOF:

TABLETS MANUFACTURING DEFECTS CAUSES AND REMEDIES THEREOF Prof. D. M. Shinkar Assistant Professor, Department of Pharmaceutics, KCT’S R.G.S.College of Pharmacy, Anjaneri, Nashik, Maharashtra. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

FEATURES:

FEATURES Tablets are solid dosage form playing key role often in first place among all over dosage forms. They having more stability, reliability. Easy to use, administer and packaging. Suitable to all controlled dosage forms. Favors towards manufacturing and technology of others. Prefers rough handling. Maximum output in short period of time. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

Sources of Tablet Defects:

Moisture Improper drying High speed machines Tools setting problem Excess use of binders Lack of proper lubricant selection Air interaction Lack of knowledge Improper training Size, shape Chipped edge Crack Print defect Smidged printing Metal fragment Breakline defect Colour spot Hair / fiber Coat mottle Abnormal ratio of excipients Sources of Tablet Defects 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

Problem in tablets are either related to imperfections in any one or more of the following factors:

Problem in tablets are either related to imperfections in any one or more of the following factors I. Tableting process related problems Capping Lamination / Laminating Cracking II. Excipient related problems Chipping Picking Sticking Binding Mottling Poor flow Weight variation Granule size and size distribution before compression Poor mixing III. Machine related problems Double impression Punch variation Hardness variation 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

1. CAPPING :

1. CAPPING Capping happened when the upper or lower segment of the tablet separates horizontally, either partially or completely from the main body of a tablet and comes off as a cap, during ejection from the tablet press, or during subsequent handling. Reason: Capping is usually due to the air – entrapment in a compact during compression, and subsequent expansion of tablet on ejection of a tablet from a die. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

CAPPING RELATED TO ‘FORMULATION’ (GRANULATION):

CAPPING RELATED TO ‘FORMULATION’ (GRANULATION) Sr. No. CAUSES REMEDIES 1. Large amount of fines in the granulation Remove some or all fines through 100 to 200 mesh screen 2. Too dry or very low moisture content (leading to loss of proper binding action). Moisten the granules suitably. Add hygroscopic substance e.g.: sorbitol, methyl- cellulose or PEG-4000. 3. Not thoroughly dried granules. Dry the granules properly. 4. Insufficient amount of binder or improper binder. Increasing the mount of binder OR Adding dry binder such as pre-gelatinized starch, gum acacia, powdered sorbitol, PVP, hydrophilic silica or powdered sugar. 5. Insufficient or improper lubricant. Increase the amount of lubricant or change the type of lubricant. 6. Granular mass too cold to compress firm. Compress at room temperature. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

CAPPING RELATED TO ‘MACHINE (DIES, PUNCHES AND TABLET PRESS):

CAPPING RELATED TO ‘MACHINE (DIES, PUNCHES AND TABLET PRESS) Sr.no CAUSES REMEDIES 1. Poorly finished dies Polish dies properly. Investigate other steels or other materials. 2. Deep concave punches or beveled-edge faces of punches. Use flat punches. 3. Lower punch remains below the face of die during ejection. Make proper setting of lower punch during ejection. 4. Incorrect adjustment of sweep-off blade. Adjust sweep-off blade correctly to facilitate proper ejection. 5. High turret speed. Reduce speed of turret (Increase dwell time). 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

2. Lamination / Laminating :

2. Lamination / Laminating Definition: ‘Lamination’ is the separation of a tablet into two or more distinct horizontal layers. Reason: Air - entrapment during compression and subsequent release on ejection. The condition is exaggerated by higher speed of turret. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

LAMINATION RELATED TO FORMULATION (GRANULATION):

LAMINATION RELATED TO FORMULATION (GRANULATION) LAMINATION RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) Sr. No CAUSES REMEDIES 1. Oily or waxy materials in granules Modify mixing process. Add adsorbent or absorbent. 2. Too much of hydrophobic lubricant e.g.: Magnesium-stearate. Use a less amount of lubricant or change the type of lubricant. Sr. No. CAUSES REMEDIES 1. Rapid relaxation of the peripheral regions of a tablet, on ejection from a die. Use tapered dies, i.e. upper part of the die bore has an outward taper of 3° to 5°. 2. Rapid decompression Use pre-compression step. Reduce turret speed and reduce the final compression pressure. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

3. Cracking :

3. Cracking Definition: Small, fine cracks observed on the upper and lower central surface of tablets, or very rarely on the sidewall are referred to as ‘Cracks’. Reason: It is observed as a result of rapid expansion of tablets, especially when deep concave punches are used. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

CRACKING RELATED TO FORMULATION (GRANULATION):

CRACKING RELATED TO FORMULATION (GRANULATION) CRACKING RELATED TO MACHINE (DIES, PUNCHES AND TABLETPRESS) Sr. No. CAUSES REMEDIES 1. Large size of granules. Reduce granule size. Add fines. 2. Too dry granules. Moisten the granules properly and add proper amount of binder. 3. Tablets expand. Improve granulation. Add dry binders. 4. Granulation too cold. Compress at room temperature. Sr. No. CAUSES REMEDIES 1. Tablet expands on ejection due to air entrapment. Use tapered die. 2. Deep concavities cause cracking while removing tablets Use special take-off. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

4. Chipping :

4. Chipping Definition: ‘Chipping’ is defined as the breaking of tablet edges, while the tablet leaves the press or during subsequent handling and coating operations. Reason: Incorrect machine settings, specially mis-set ejection take-off. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

CHIPPING RELATED TO FORMULATION (GRANULATION):

CHIPPING RELATED TO FORMULATION (GRANULATION) CHIPPING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) Sr. No CAUSES REMEDIES 1. Sticking on punch faces Dry the granules properly or increase lubrication. 2. Too dry granules. Moisten the granules to plasticize. Add hygroscopic substances. 3. Too much binding causes chipping at bottom. Optimize binding, or use dry binders. Sr. No CAUSES REMEDIES 1. Groove of die worn at compression point. Polish to open end, reverse or replace the die. 2. Barreled die (center of the die wider than ends) Polish the die to make it cylindrical 3. Edge of punch face turned inside/inward. Polish the punch edges 4. Concavity too deep to compress properly. Reduce concavity of punch faces. Use flat punches. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

5. Picking :

5. Picking Definition: ‘Picking’ is the term used when a small amount of material from a tablet is sticking to and being removed off from the tablet-surface by a punch face. The problem is more prevalent on the upper punch faces than on the lower ones. The problem worsens, if tablets are repeatedly manufactured in this station of tooling because of the more and more material getting added to the already stuck material on the punch face. Reason: Picking is of particular concern when punch tips have engraving or embossing letters, as well as the granular material is improperly dried. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

PICKING RELATED TO FORMULATION (GRANULATION) :

PICKING RELATED TO FORMULATION (GRANULATION) Sr.No CAUSES REMEDIES 1. Excessive moisture in granules. Dry properly the granules, determine optimum limit. 2. Too little or improper lubrication. Increase lubrication; use colloidal silica as a ‘polishing agent’, so that material does not cling to punch faces. 3. Low melting point substances, may soften from the heat of compression and lead to picking. Add high melting-point materials. Use high meting point lubricants. 4. Low melting point medicament in high concentration. Refrigerate granules and the entire tablet press. 5. Too warm granules when compressing. Compress at room temperature. Cool sufficiently before compression. 6. Too much amount of binder. Reduce the amount of binder, change the type or use dry binders. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

PICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS):

PICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) Sr.No CAUSES REMEDIES 1. Rough or scratched punch faces. Polish faces to high luster. 2. Embossing or engraving letters on punch faces such as B, A, O, R, P, Q, G. Design lettering as large as possible. Plate the punch faces with chromium to produce a smooth and non-adherent face. 3. Bevels or dividing lines too deep. Reduce depths and sharpness. 4. Pressure applied is not enough; too soft tablets. Increase pressure to optimum. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

6. Sticking:

6. Sticking Definition: ‘Sticking’ refers to the tablet material adhering to the die wall. Filming is a slow form of sticking and is largely due to excess moisture in the granulation. Reason: Improperly dried or improperly lubricated granules. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

STICKING RELATED TO FORMULATION (GRANULATION):

STICKING RELATED TO FORMULATION (GRANULATION) Sr. No. CAUSES REMEDIES 1. Granules not dried properly. Dry the granules properly. Make moisture analysis to determine limits. 2. Too little or improper lubrication. Increase or change lubricant. 3. Too much binder Reduce the amount of binder or use a different type of binder. 4. Hygroscopic granular material. Modify granulation and compress under controlled humidity. 5. Oily or way materials Modify mixing process. Add an absorbent. 6. Too soft or weak granules. Optimize the amount of binder and granulation technique. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

STICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS):

STICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) Sr. No. CAUSES REMEDIES 1. Concavity too deep for granulation. Reduce concavity to optimum. 2. Too little pressure. Increase pressure. 3. Compressing too fast. Reduce speed. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

7. Binding:

7. Binding Definition: ‘Binding’ in the die, is the term used when the tablets adhere, seize or tear in the die. A film is formed in the die and ejection of tablet is hindered. With excessive binding, the tablet sides are cracked and it may crumble apart. Reason: Binding is usually due to excessive amount of moisture in granules, lack of lubrication and/or use of worn dies. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

BINDING RELATED TO FORMULATION (GRANULATION):

BINDING RELATED TO FORMULATION (GRANULATION) Sr.No CAUSES REMEDIES 1. Too moist granules and extrudes around lower punch. Dry the granules properly. 2. Insufficient or improper lubricant. Increase the amount of lubricant or use a more effective lubricant. 3. Too coarse granules. Reduce granular size, add more fines, and increase the quantity of lubricant. 4. Too hard granules for the lubricant to be effective. Modify granulation. Reduce granular size. 5. Granular material very abrasive and cutting into dies. If coarse granules, reduce its size. Use wear-resistant dies. 6. Granular material too warm, sticks to the die. Reduce temperature. Increase clearance if it is extruding. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

BINDING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS):

BINDING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) Sr.No . CAUSES REMEDIES 1. Poorly finished dies. Polish the dies properly. 2. Rough dies due to abrasion, corrosion. Investigate other steels or other materials or modify granulation. 3. Undersized dies. Too little clearance. Rework to proper size. Increase clearance. 4. Too much pressure in the tablet press. Reduce pressure. OR Modify granulation. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

7. Mottling :

7. Mottling Definition: ‘Mottling’ is the term used to describe an unequal distribution of color on a tablet, with light or dark spots standing out in an otherwise uniform surface. Reason: One cause of mottling may be a colored drug, whose color differs from the color of excipients used for granulation of a tablet. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

Causes And Remedies Of Mottling::

Causes And Remedies Of Mottling: Sr.No . CAUSES REMEDIES 1. A coloured drug used along with colourless or white- coloured excipients. Use appropriate colourants . 2. A dye migrates to the surface of granulation while drying. Change the solvent system, Change the binder, Reduce drying temperature and Use a smaller particle size. 3. Improperly mixed dye, especially during ‘Direct Compression’. Mix properly and reduce size if it is of a larger size to prevent segregation. 4. Improper mixing of a coloured binder solution. Incorporate dry colour additive during powder blending step, then add fine powdered adhesives such as acacia and tragacanth and mix well and finally add granulating liquid. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

8. Weight variation:

8. Weight variation The weight of the tablet being compressed is determined by the amount of granulation in the die prior to the compression . Therefore any thing that alter the die filling process can alter tablet weight and weight variation. Improper blending of granules. Lack of sufficient amount of lubricant . Abnormal uniform mixing of all excipients. Improper tool setting of machine. Hi-speed running of machine. Improper glidant selection. Abnormal size of granules. Improper drying making tablet with different weight. Heavy input in Hooper. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

9. Print defect :

9. Print defect It is mainly observed in tablets which having hard corners/designs on punches. It takes due to improver punch cycle. Punches having rough surface . Improper blending of total powder. Letter are designed with uneven surfaces on punches. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

10. Poor flow:

10. Poor flow Depending on the flow of granulation from hopper to the die cavity must be uniform and continuous. Similarly dies are not filled properly if machine speed is in excess. Two main causes of poor flow are – Arching or bridging and Rat holing Remedies- By addition of lubricants By inserting vibrators to the Hooper. 11. Poor mixing If lubricants and glidants are nor properly distributed . There is tendency to minimize the mixing time during lubricant addition to prevent or reduce the granulation friability; however inadequate mixing leads to unsatisfactory granulation. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

12. Granule size and distribution:

12. Granule size and distribution Variations in the ratio of small to large granules and in magnitude of difference between granule size influences the how the void spaces between particles are filled. Different proportions of size of granules/particles in the die filling process may leads to weight variation. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

13. Double impression:

13 . Double impression Definition: ‘Double Impression’ involves only those punches, which have a monogram or other engraving on them. Reason: At the moment of compression, the tablet receives the imprint of the punch. Now, on some machines, the lower punch freely drops and travels uncontrolled for a short distance before riding up the ejection cam to push the tablet out of the die, now during this free travel, the punch rotates and at this point, the punch may make a new impression on the bottom of the tablet, resulting in ‘Double Impression’. If the upper punch is uncontrolled, it can rotate during the short travel to the final compression stage and create a double impression. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

CAUSES AND REMEDIES OF DOUBLE IMPRESSION::

CAUSES AND REMEDIES OF DOUBLE IMPRESSION: Sr. No. CAUSE REMEDIES 1. Free rotation of either upper punch or lower punch during ejection of a tablet. -Use keying in tooling, i.e. inset a key alongside of the    punch, so that it fits the punch and prevents punch rotation. -Newer presses have anti-turning devices, which prevent punch rotation. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

14. Punch variation:

14. Punch variation When lower punches are of uneven length – the difference may be only few thousands of an inch- the fill in each die varies because the fill is volumetric. Only a good punch and die control can provide tooling of uniform dimensions. 15. Hardness variation It depends on the weight of material and the space between the upper and lower punches at the time of compression. 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

PowerPoint Presentation:

Thank You If you salute your duties, No need to salute anybody If you don’t salute your duties, You have to salute everybody. [email protected] 1/7/2013 Prof. D. M. Shinkar, KCT'S R.G.S.College Of Pharmacy, Nashik.

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