Thursday, January 28, 2021

Weight Variation During Tablet Compression.

Weight variation is a frequently used term during tablet compression operation in pharmaceutical industries.

As the name indicates Weight Variation is a defect in which weight differs from the defined ranges given by the  official pharmacopoeias.


According to USP

Weight variation ranges according to USP are as follow,


Tablet Weight(mg)

%age Difference

130 or less than 130

10%

130 to 324

7.5%

Above 324

5%


According to BP

Weight variation ranges according to BP are as follow,


Tablet Weight(mg)

%age Difference

80 or less than 80

10%

More than 80 & less than 250

7.5%

250 or above 250

5%


If the weight of  tablets is higher than the recommended range then the assay or content uniformity may also be high.

&

If the weight of  tablets is lower than the recommended range then the assay or content uniformity may also be low.


So weight of tablets should carefully be monitored during compression operation.


In this article we will discuss some main  reasons which may result in weight  variation of tablets during compression operation.


Weight Variation During Tablet Compression.


1. Formulation Related

  • More Fine

  • High Moisture Content

  • Granules Size


2. Machine Related

  • Hoper Adjustment

  • Blockage Of Feeding Housing

  • Feeding Rate


1. Formulation Related

Formulation related means the factors which occur during the manufacturing stage.

Manufacturing of granules by wet granulation is a multistep process and variation in any step may directly affect the compression stage.

So each and every stage of granulation should be carried out with great care to make the compression process trouble free and smooth.

Following are some formulation related important factors which may result in weight variation.


More Fine

  • More fine means our final product has less granules and more fine powders.

  • If we have more fine in our formulation it may result in poor flow of product from compression machine hoper to the feeder.

  • More fine may also result in a rat hole.

  • Rat hole is a defect in which powder adheres to the walls of the hoper and in the middle a hole is formed like the hole of a rat.

  • So due to poor flow or rat hole, dies are not properly filled during compression and results in weight variation.


Solution

  • There should be a proper ratio of fine powder and granules to improve flow and to prevent weight variation.


High Moisture Content

  • High moisture content is another factor which may result in weight variation during compression operation.

  • If moisture content is not properly removed from the final product it may result in a rat hole.

  • As mentioned above, rat hole is a flow defect and results in weight variation.


Solution

  • Moisture should be properly removed during the drying process.


Granules Size 

  • Granules size is another factor which may result in weight variation during tablet compression.

  • For small size tablets if we use large size granules it will result in improper die filling and improper die filling results in weight variation.

  • For large size tablets if we use small size granules it may also result in weight variation of tablet during tablet compression.


Solution

  • Granules size should be suitable according to tablet size for proper die filling.


Also Read: 

Reasons and solutions of tablet capping.


Reasons and remedies of tablet sticking and picking.



2. Machine Related

Machine related reasons for weight variation means that the final product which we have manufactured is fault free but the machine parts or tooling is creating weight variation of the tablets.

Following are some machine related important factors which may result in weight variation.


Hoper Adjustment

  • Hoper position may result in weight variation in case of conventional compression machines where powder or granules flow through the hoper to the machine feeder under the influence of gravity.

  • If the hoper base is low it may result in poor feeding of powders or granules and results in weight.


Solution

  • Hopers of compression machines should be adjusted in such a way  that powders or granules should flow smoothly under influence of gravity.


Blockage of Feeder housing

  • In conventional compression machines during normal compression operation, sudden blockage of any housing in the feed frame results in weight variation due to less supply of powders or granules to the dies.


Solution

  • Flow through feeder housing should be critically monitored and in case of any blockage compression machine should immediately be stopped.


Feeding Rate

  • In advance compression machines powder from feed frame to dies is supplied through force feeding system.

  •  If the rpm of the force feeding system is very low and machine speed is high, proper feeding to dies will be distrubed and results in weight variation.


Solution

  • Powders or granules feeding system should be synchronized with compression machine speed to balance the die filling and compression machine speed.


Also Read: 


Stages and Mechanism of Tablet Compression.


Advancements in tablet compression machines.


Calculation of compression machine capacity.


Wednesday, January 27, 2021

Methods Of Bidder Addition For Wet Granulation

Binders are the most important excipients used to combine powder particles with each other to form granules in wet granulation.

Wet granulation is the most commonly used method of manufacturing granules for tablets and capsules in pharmaceutical industries.


Methods Of Bidder Addition For Wet Granulation


To learn complete wet granulation method read following,

Description of wet granulation.


In wet granulation binder can be added in powder premix in the following ways,


  • Binder Solution/Suspension

  • Dry Powder Activation 

  • Dry Powder+Binder Solution/Suspension

  • Binder Paste

  • API In Solvent

  • Solvent Alone


Binder Solution/Suspension

Binders used for wet granulation are in solid powder form and are mixed in a suitable solvent either aqueous or organic depending upon the formulation.

Binder in form of Solution/Suspension

is the most commonly and widely used method for binder preparation.


Example

  •  Kollidon


Method Of Preparation

  • Take the required amount of binder according to BMR.

  • Sieve the binder if required(Varry material to material)

  • Measure required quantity of solvent according to BMR.

  • Add powder material slowly in solvent using a propeller or homogenizer mixer.

  • Mix until a solution or lumps free suspension is prepared.

  • It is ready for use and adds it slowly in powder premix in a controlled manner.

  • Too fast addition rate may result in localized over-wetting or Case Hardening. 


Dry Powder Activation 

Dry Powder activation is a method of binder addition in which binder in powder form is mixed in a premix of powder and is activated by the solvent.


Examples



Method Of Addition

  • Binder quantity is taken according to BMR.

  • It is sieved and added in premix(API+Diluent+Disintegrant etc) ready for granulation.

  • After uniform mixing of binder material with premix (API+Diluent+Disintegrant etc) add a measured quantity of solvent(water or organic solvent) in the premix.

  • This solvent addition activates the binder present in premix and binds powders to form granules. (Chances of case hardening are minimised).


Dry Powder Activation+Binder Solution/Suspension

  • It is a combination of the above two methods.

  • Sometimes all the binder quantity is not added in solution or suspension form because it may result in a too viscous solution or suspension difficult to pour.

  • So to avoid this some quantity is added in solvent and remaining is added in dry form in the premix.


Binder Paste

In this method the binder is added in the form of paste.


Example

Common example is Starch paste.


Method Of Preparation

  • Simple starch is not soluble in cold water.

  • Starch is added in water and mixed.

  • It is then heated at a suitable temperature to form a paste.

  • Paste formed is then cooled and added in powder premix to form granules.


API In Solvent

  • For some formulations, API can be added in suitable solvent depending upon the formulation and is poured or sprinkled over powder premix to form granules.

  • It is usually used to improve the uniform distribution of API in the formulation.


Solvent Alone

In this method, formulation requires no binder.

Only Addition of suitable solvent is sufficient to activate granules formation.


Popular Posts:


Advancements Granulation Techniques.


End point determination or wet granulation.



Tuesday, January 26, 2021

Meglumine

Meglumine is less common and not a well-known excipient because it is not commonly used in most of pharmaceutical formulations.

About 70% of pharmacists working in pharmaceutical industries may not be aware of this excipient but its importance can not be ignored because of those drugs which have poor aqueous solubility.

Meglumine is amino sugar derived from sorbitol.

It is also known as

  • Meglumine

  • Megluminum


Functions of Meglumine

Meglumine is used in different solid and liquid dosage forms as


  • Organic Base

  • To Enhance Aqueous Solubility of API.

  • pH adjusting agent

  • Stabilizer

  • To improve stability 

  • X ray contrast media

  • Solubilizing Agent


Appearance

Meglumine appears as white to slightly yellowish crystalline powder.


Solubility

Meglumine is water soluble but insoluble in chloroform.


Storage

  • Meglumine should be stored in well-closed containers.

  • It should not be stored in containers made of Aluminium because it reacts with aluminium and releases the hydrogen gas.

  • It also reacts with copper containers and the colour of meglumine is changed.

  • It should be stored in Stainless Steel containers.


Incompatible

Meglumine is incompatible with Glipizide.

(Ref Handbook of Pharmaceutical Excipients)


Also Read: 

Classification of Excipients.

Role of diluents in tablet granulation.



Meglumine


Meglumine & Telmisartan

  • Telmisartan is an API which is used to treat high blood pressure.

  • Telmisartan is poorly soluble in GIT.

  • Bioavailability of Telmisartan is pH-dependent and it is poorly soluble at 3-7 pH. 

  • So Meglumine is used as a basic or alkalizing agent to create basic media and to enhance solubility and bioavailability of Telmisartan.

  • For proper solubility enhancement of Telmisartan, it should form a complex with meglumine.

How to Enhance the Solubility of Telmisartan?

As mentioned above solubility of telmisartan is increased by using meglumine but here is an important practical observation that using only meglumine is not the science to enhance the aqueous solubility of Telmisartan but the exact complex formation is the key point.

Following steps should be followed to improve solubility.

  • The first critical step is to always use meglumine and telmisartan after sieving.

  • Do not mix any other excipient with Telmisartan and Meglumine during initial sieving because it will not form a proper complex.

  • Mix Meglumine and telmisartan before sieving.

  • Sieve the pre-mix through a fine mesh.

  • Sieving should be done by applying pressure and for this avoid manual sieving.

  • Use an oscillating granulator with a fine mesh.

  • When pre mix of telmisartan and meglumine is sieved then mix other excipients with the premix and again sieve it.

  • After this mix it in a suitable mixer and proceed further steps of wet granulation.

(Ref practical observations)


Also Read: 

Wet granulation & Dry  Granulation in pharmaceutical industries.


Advancements Granulation Techniques.



Sunday, January 24, 2021

Hydroxypropyl Cellulose|HPC

Hydroxypropyl Cellulose is a derivative of cellulose and it is used as an excipient in different pharmaceutical dosage forms.USP 32 NF-27 defines the HPC as a partially substituted derivative of cellulose and it may contain not more than 0.6% Silica or any other anticaking agent.


Other Names

HPC is also known

  • Klucel

  • hyprolose

  • HPC


Functions Of  HPC

HPC is used as


  • Tablet and Capsule Binder.

  • As Matrix For Extended Release Formulations.

  • Film Former.

  • Suspending and Thickening agent


Tablet and capsule binder

  • HPC or klucel is used as a binder for tablet and capsule formulation for both dry and wet granulation.


Hydroxypropyl Cellulose|Klucel|HPC


  • In wet granulation, it may be added in dry mixing before kneading and can be activated by addition of solvent.

  • It is also used as a binder for wet granulation in the form of solution.

  • The concentration of HPC used as a binder is 2-6% for wet and dry granulation.


Note

  • HPC is water-soluble but when it is added in water it may form a gel at the start and take time to dissolve to form a clear solution.

  • Following method can be used to form a clear solution of HPC in water in a short period.

  • For this slurry of HPC is prepared in hot water or glycerin.

  • Prepare a slurry of HPC in hot water at 50-60°C and don't exceed the temperature above  60°C. 

  • Stir the soaking material for a few minutes and maintain the slurry at a temperature, not below 50°C.

  • Add this slurry in Cold water with slow stirring.

  • It will produce a clear, lump-free solution in a short period to reduce the binder preparation time of HPC.

  (Ref Ashland)


Also Read: 

GMP vs cGMP and 21 CFR.


Qualification|FAT|SAT|DQ|IQ|OQ|PQ


As Matrix For Extended Release

  • Hydroxypropyl Cellulose is used as a control release agent to slow the release of drugs.

  • On contact with water, it forms a matrix and then slowly releases the drug.

  • The concentration of HPC used as a matrix is 15-35%.

  • As the viscosity of HPC increases, the release rate of drug decreases.

  • A surfactant added in the solution of HPC increases its viscosity and drug release is decreased.


Film Former

  • HPC is used as a film-forming polymer in tablet coating.

  • 5% aqueous solution is used for film coating.

  • Film formation by HPC is flexible without plasticiser


Suspending and Thickening agent

  • HPC is also used as a thickening and suspending agent.


Solubility 

  • Hydroxypropyl Cellulose is soluble in the water and polar organic solvents.

  • It is soluble in the water below 38°C but it is insoluble at a temperature between 40-45°C.


Stability

  • An aqueous solution of HPC may promote mould growth so it is recommended to use an antimicrobial agent for aqueous solutions.

  • Organic solutions do not promote antimicrobial growth.  


Incompatible

  • Hydroxypropyl Cellulose is incompatible with Methyl paraben and Propyl Paraben.


Grades Of Klucel

  • Klucel is available in different grades.

  • 7 viscosity types are as follow


  • EL

  • E

  • L

  • J

  • G

  • M

  • H


The product name is expressed by a combination letter system.First letter indicates viscosity type then second letter indicates particle size and at the last letter represent market segment e.g


           Klucel HF Pharm 


H represents grade F Pharm to represent pharmaceuticals.

Fine particle size is expressed by X.


Klucel MXF Pharm

(Ref Ashland)


Following are grades of Klucel


  • Klucel HF

  •  Klucel MF

  • Klucel GF

  • Klucel JF

  • Klucel LF

  • Klucel EF


(Ref Handbook of Pharmaceutical Excipients)


Hydroxypropyl Cellulose Low substituted (L-HPC)


Low substituted Hydroxypropyl Cellulose is also known as L-HPC and is the derivative of cellulose which contains less substitution of hydroxypropyl as compared to HPC.


Solubility

HPC is soluble in water but L-HPC swells in water and is insoluble in water.


Other Names

  • L-HPC

  • Hyprolose

  • Low Substituted


Function

Low substituted Hydroxypropyl Cellulose is used as

 

  • Tablet and Capsule Disintegrant.

  • Tablet and Capsule Binder.


Grades Of L-HPC

L-HPC is available in different viscosity grades and particle sizes which are as follow,


  • LH-11

  • LH-21

  • LH-31

  • LH-B1

  • LH-22

  • LH-32


LH-11

  • LH-11 has long fibrous particles.

  • LH-11 is used as a Disintegrant for Direct compression.

  • LH-11 is used as an anti-Capping agent for direct compression.


LH-21


  • In LH-21 quantity of fibres is less.

  • LH-21 is used as Binder in wet granulation

  • LH-21 is used as a disintegrant in wet granulation.


Also Read: 


Colloidal Silicon Dioxide|Aerosil


HPMC|Methocel



LH-31

  • LH-31 has a small particle size.

  • It is used in the extrusion process to produce granules.


LH-B1

  • It is non-fibrous.

  • Its density is high.

  • It is suitable for FBD process and direct compression method.


LH-22

  • Give better disintegration.


LH-32

  • Give better disintegration.


Incompatibility

  •  L-HPC is Incompatible with alkaline substances and formulations containing L-HPC and alkaline substances may result in prolong disintegration time.