Tablet formulation design is a critical job which requires extensive knowledge of the excipients and active pharmaceutical ingredients which are used for tabet manufacturing.
A formulator must have knowledge of the manufacturing process and must be equipped with the skills to troubleshoot the problems which are encountered during the manufacturing of the tablet batches.
How to design or develop a basic formulation for tablets is the most frequently asked question?
In this article we will learn briefly about the key points which must be remembered during the table formulation and we will learn how we can design a basic formulation for any tablet batch & how we can add further improvements in the formula to overcome all the issues related to the tablets specifications.
First of all you must have a brief overview of all the excipients which are used in the tablet manufacturing and then we will try to design a simple formulation. The formulation design will be as simple as any one one can design a basic formulation for tablets and can improve it depending on the quality control results.
The basic aim of this article is to make everyone skillful to develop or design a prototype formulation of tablets.
Following classes of excipients are used for the tablet manufacturing,
- Diluents
- Binders
- Disintegrants
- Lubricants
- Glidants
- Colourants
Diluent
Diluents are also known as bulking agents or filler and are those materials or excipients which are used to make up the final bulk volume.
Examples
The common examples of the diluents are lactose, dextrose, mannitol and starch.
Disintegrants
Disintegrants are added in the tablet formulation and these are the excipients which facilitate the breakdown of the tablet into small fragments and help to release drugs.
Apart from conventional disintegrants which are required in high quantities the advanced type of disintegrants are known as super disintegrants which give the same effect in less quantity.
Examples
Commonly used disintegrants are starch,clay and super disintegrants are pregelatinized starch,croscarmellose sodium, sodium starch glycolate.
Binders
Binders are excipients used for tablet formulation and give cohesiveness to the powder to form the granules.
Binders are of three types,
- Natural
- Synthetic
- Semi Synthetic
Examples
- Gums
- Gelatin
- Starch
- HPC
- HPMC
- Kollidon
Lubricants
Lubricants are ingredients which are used to reduce the friction between the product and machine parts.These are used to prevent the tablet sticking.
Example
Magnesium stearate
Glidants
Glidants are the excipients which are used to reduce interparticle friction.These excipients reduce inter particle friction and enhance the flow that is why glidants are also known as flow promoters.
Example
- Talc
- Colloidal silicon dioxide
Colourants
Colors are used in tablet formulation to give a unique and distinguished color for brand identification.
FD&C colors are used in the formulation.
How To Design a Tablet Formulation
Now we will learn to design a basic formulation for tablets.If you understand these basics of formulation design then it will not be difficult for you to formulate a tablet recipe on an advanced level.
The purpose of the formulation is to design a tablet which must comply all the specifications and thess specifications include,
- Assay
- Content uniformity
- Weight Variation
- Disintegration Time
- Dissolution Profile
The flow properties must be good, there should be no weight variation and there should be trouble free compression and coating process.
At the stage of formulation design our aim must be to get the tablet which complies with all the above mentioned specifications.
Practical Example
Suppose we want to design a formulation for a batch of tablets containing API ‘X’ and strength of API is 500 mg.We will use wet granulation method.
Now we will define what will be the tablet compression weight and suppose our requirement is to compress it at 750mg.
Now we have completed some basics of the formulation and we are familiar that our API quantity is 500 mg and compression weight will be 750 mg so.
750mg – 500mg (API) = 250 milligram
From the above values we are now familiar that we can add 250 mg of the excipients (which we discussed above) to get all the required tablet attributes.
6 Pillars Of Tablet Formulation
We will design simple & prototype formulation on the following 6 Pillars.
- Active Pharmaceutical Ingredient (API)
- Binders
- Disintegrants
- Lubricants
- Glidants
- Diluent
Raw Materials Calculation For Tablet formulation
After API quantity, the second step is to select the binder & its quantity along with solvent.We take water as a solvent and for binder we have selected the kollidon.
Suppose we add 2% binder so 15 mg/tablet will be the binder quantity and now remaining excipients quantity will be
750 mg (Total tablet weight) – 500 mg (API) -15 mg (Binder) = 235 mg
Now on the 3rd stage we will add disintegrants to the formulation and suppose we have selected sodium starch glycolate as super disintegrant and its quantity is 4 % so 30 mg will the
quantity of disintegrant and remaining excipients will be
750 mg (Total tablet weight) – 500 mg (API) -15 mg (Binder) – 30 mg (disintegrant) = 205 mg
Now we will add next ingredient which is glidant and suppose we use colloidal silicon dioxide 1% so
750 mg (Total tablet weight) – 500 mg (API) -15 mg (Binder) – 30 mg (disintegrant) – 7.5 mg (glidants ) = 197.5 mg.
Now we will add our fifth pillar of formulation which is lubricant
and we will add Mg stearate as lubricant and quantity will be 1.2 % so 9 mg per tablet will be the lubricant and remaining excipients will be
750 mg (Total tablet weight) – 500 mg (API) -15 mg (Binder) – 30 mg (disintegrant) – 7.5 mg (glidant) –
9 mg (lubricant) = 188.5mg
Now is the final step where we will add the main pillar of our formulation which is diluent.At start of this article we have discussed that diluents are those excipients which are used to make up final bulk volume so here volume make up will be done with diluent.
Suppose we add microcrystalline cellulose as diluent or filler and its quantity will be 188.5 mg so
750 mg (Total tablet weight) -500 mg (API) -15 mg (Binder) – 30 mg (disintegrant) – 9 mg (Lubricant) – 7.5 mg ( glidant) – 188.5 mg (diluent) = 0.0 mg
By using all the above mentioned excipients we will prepare a trial for tablet manufacturing by wet granulation method and after final blending we will submit the blend sample to the quality control department for analysis.
All the required testings for the final blend as per pharmacopeia will be performed and when it will pass all the required tests then it will be released for compression.
A sample of compressed tablets will again be tested for all the required testings including disintegration and Dissolution profile.
If the required results for blend or compressed tablets are not within specifications then will review our formulation depending upon the situation to bring the results with specifications.
We will use the formulation for scale up batch for which all the results of blend, compression and coating are passed.
Conclusion
Tablet formulation design is a complex process and requires extensive experience and knowledge of various raw materials.To develop a simple formulation we require API, binders, disintegration,glidants and diluents.Improvements in formulation are done on the basis of trial results.