Problems in tablet manufacturing

Problems in tablet manufacturing

Introduction

(62,63)

An ideal tablet should be free from any visual

defect or functional defect. The advancements and innovations in tablet manufacture have not decreased the problems, often encountered in the production, instead have increased the problems, mainly because of the complexities of tablet presses; and/or the greater demands of quality.

An industrial pharmacist usually encounters number of problems during manufacturing. Majority of visual defects are due to inadequate fines or inadequate moisture in the granules ready for compression or due to faulty machine setting. Functional defects are due to faulty formulation. Solving many of the manufacturing problems requires an in–depth knowledge of granulation processing and tablet presses, and is acquired only through an exhaustive study and a rich experience.

Here, we will discuss the imperfections found in tablets along–with their causes and related remedies. The imperfections are known as: ‘VISUAL DEFECTS’ and they are either related to imperfections in any one or more of the following factors:

I. Tableting Process

II. Excipient

III. Machine

The defects related to Tableting Process are as follows:

i) CAPPING: It is partial or complete separation of the top or bottom of tablet due air-entrapment in the granular material.

ii) LAMINATION: It is separation of tablet into two or more layers due to air-entrapment in the granular material.

iii) CRACKING: It is due to rapid expansion of tablets when deep concave punches are used.

The defects related to Excipient are as follows:

iv) CHIPPING: It is due to very dry granules.

v) STICKING: It is the adhesion of granulation material to the die wall

vi) PICKING: It is the removal of material from the surface of tablet and its adherance to the face of punch.

vii) BINDING

These problems (v, vi, vii) are due to more amount of binder in the granules or wet granules.

The defect related to more than one factor:

viii) MOTTLING: It is either due to any one or more of these factors: Due to a coloured drug, which has different colour than the rest of the granular material? (Excipient- related); improper mixing of granular material (Process-related); dirt in the granular material or on punch faces; oil spots by using oily lubricant.

The defect related to Machine:

ix)DOUBLE IMPRESSION: It is due to free rotation of the punches, which have some engraving on the punch faces.

Further, in this section, each problem is described along-with its causes and remedies which may be related to either of formulation (granulation) or of machine (dies, punches and entire tablet press).

Capping

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‘Capping’ is the term used, 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.

TABLE.1 THE CAUSES AND REMEDIES OF CAPPING RELATED TO ‘FORMULATION’ (GRANULATION)

TABLE.2. THE CAUSES AND REMEDIES OF CAPPING RELATED TO ‘MACHINE’ (DIES, PUNCHES AND TABLET PRESS)

Lamination / Laminating

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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.

TABLE.3. THE CAUSES AND REMEDIES OF LAMINATION RELATED TO FORMULATION (GRANULATION)

TABLE.30. The Causes and Remedies of Lamination related to MACHINE (Dies, Punches and Tablet Press)

Chipping

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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.

TABLE.31. THE CAUSES AND REMEDIES OF CHIPPING RELATED TO FORMULATION (GRANULATION) ARE AS FOLLOWS

Cratering

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Definition: It is defect of film coating whereby volcanic-like craters appears exposing the tablet surface.
Reason: The coating solution penetrates the surface of the tablet, often at the crown where the surface is more porous, causing localized disintegration of the core and disruption of the coating.

TABLE.45. THE CAUSES AND REMEDIES OF CRATERING

Picking:

Definition: It is defect where isolated areas of film are pulled away from the surface when the tablet sticks together and then part.
Reason: Conditions similar to cratering that produces an overly wet tablet bed where adjacent tablets can stick together and then break apart.

TABLE.46. THE CAUSES AND REMEDIES OF PICKING

Blooming:

Definition: It is defect where coating becomes dull immediately or after prolonged storage at high temperatures.
Reason: It is due to collection on the surface of low molecular weight ingredients included in the coating formulation. In most circumstances the ingredient will be plasticizer.

TABLE.48. THE CAUSE AND REMEDY OF BLOOMING

Orange peel/Roughness:

Definition: It is surface defect resulting in the film being rough and nonglossy. Appearance is similar to that of an orange.
Reason: Inadequate spreading of the coating solution before drying.

TABLE.52. THE CAUSES AND REMEDIES OF ORANGE PEEL/ROUGHNESS

Cracking/Splitting:

Definition: It is defect in which the film either cracks across the crown of the tablet (cracking) or splits around the edges of the tablet (Splitting)
Reason: Internal stress in the film exceeds tensile strength of the film.
TABLE.53. THE CAUSE AND REMEDY OF CRACKING/SPLITTING

Key Phrases

• During tablet manufacture, an industrial pharmacist usually encounters many problems. Solving these problems requires an in-depth knowledge of tablet-formulation as well as machine-operating processes.

• Capping and Lamination are the defects arising as a result of air-entrapment in the granular material.

• Chipping is a defect related arising due to very dry granules.

• Cracking is due to rapid expansion of tablets, when deep concave punches are used.

• Sticking, Picking and Binding are the imperfections related to more amount of binder in granules.

• Mottling is an imperfection arising due to more than one factor: a coloured drug, dirt in granules or the use of an oily lubricant.

• Double-Impression is related to a machine defect: it is caused by the free rotation of punches that have some engraving on the punch-faces.

Coating defects:

• Blistering is related to entrapment of gases in or underneath the film due to overheating either during spraying or at the end of the coating run. Use of mild drying conditions can solve this problem.

• Chipping is related to higher degree of attrition associated with the coating process. Increase in hardness of the film by increasing the molecular weight grade of polymer can solve this problem.

• Cratering is related to penetration of the coating solution into the surface of the tablet, often at the crown where the surface is more porous, causing localized disintegration of the core and disruption of the coating. Decrease in spray application rate and use of optimum and efficient drying conditions can solve this problem.

• Pitting is defect in which temperature of the tablet core is greater than the melting point of the materials used in tablet formulation. Dispensing with preheating procedures at the initiation of coating and modifying the drying (inlet air) temperature can solve this problem.

• Blooming or dull film is generally because of higher concentration and lower molecular weight of plasticizer. So use lower concentration and higher molecular grade of plasticizer.

• Blushing/Whitish specks/Haziness of the film is related to precipitation of polymer exacerbated by the use of high coating temperature at or above the thermal gelation temperature of the polymers.

• Colour variation is because of improper mixing, uneven spray pattern, insufficient coating or migration of soluble dyes during drying. Geometric mixing, mild drying conditions and reformulation with different plasticizers can solve this problem.

• Infilling is because of bubble/foam formation during air spraying of a polymer solution. Addition of alcohol or use of spray nozzle capable of finer atomization can solve this problem.

• Orange peel/Roughness is related to inadequate spreading of the coating solution before drying. So decrease in viscosity of coating solution can counter this defect.

• Cracking is seen when internal stresses in the film exceeds tensile strength of the film. This is common with higher molecular weight polymers or polymeric blends. So use lower molecular weight polymers or polymeric blends.

Reference: The Theory and Practice of Industrial Pharmacy By Lachman and Lieberman (3rd Editn) 

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