The APIs cannot be provided at larger particle size. Using high conc. of starch paste + povidone sol. increased the hardness a little bit but still low hardness and high friability persist. Is there any excipient that would help in that case specially if it`s preferred for direct compression formulation?
what is the target weight of your tablet?
API conc? and excipient conc?is your API hygroscoic?
1) Try first mixing API with colloidal silicon dioxide (CSD) to improve flow rate of the API for Direct Compression at 0.5-1% of CSD.
2) Use as a main excipient the ones that have the best compressibility properties available in the market: Avicel PH 200>Microcelac (or Cellactose) > Coprocessed mixes such as PROSOLV EASY TAB SP (containing MCC, CSD, SSG, and SSF) in a proportion drug:excipient 30:70 at least.
3) Use a mix of magnesium stearate (1% of total Tablet weight)+ stearic acid (1%) + coloidal silicon dioxide (0.5%) as a lubricant mix.
In case of lack of success in the Direct Compression process, you can also try wet granulation with stronger binders as methylcellulose (Methocel A) or hydroxipropyl cellulose (Klucel), low viscosity grades, and/or use direct compression excipients as in 2) out of the wet granulation to improve Tablet strenght, this in the worst case. Optimise your formulation with Experimental Design to reduce costs. I hope this helps you and Good Luck.
The moisture content of your powder is also an important issue, too low or too high content affects the tablet hardness negatively. If the powder is fine, the poor flow properties and the expansion of the entrapped air after compression could be another reason of the low tablet hardness. Improvment of the flow properties with better flowing silicified microcrystalline cellulose (Prosolv SMCC 90) and decreasing the speed of compression to let enough time for bond consolidation may have positive effect.
You can use Pan excea MHC 300G excipient make- J.T.Baker which is co-processed excipient of Microcrystalline cellulose, HPMC adn cross povidone which improves flow of powder blend as well as hardness and friability.
Because it contains combination of binder an flow modifier and this excipient is generally used for improving hardness and friability of fine powdered API. Optimize the tablet depending upon tablet weight of your formulation.
Hope this will help you in formulating tablet.
I agree with Mr. Luis Estrada-Flores. But if the problem persists, then slugging could be an option in this case.
Thank you all.
Shuaib the target weight is 1.8 g containing 1 g of calcium carbonate as the main API. No specific excipients are a must for formulation.
Sambhu and Subrata, I tried slugging, it did enhance flowability but no good hardness obtained.
New excipients such as Isomalt (Galen IQ 721 compression-direct grade or 801 for wet granulation) give stronger tablets even that MCC and can help you most. Also a mix of API with Neusilin UFL2 (Magnesium aluminum Silicate NF) sometimes gives best results instead of colloidal ilicon dioxide.s
Aerosil 0.5- 2% (colloidal silicon dioxide) can be used for direct compression.It gives you excellent hardness.
You say "a large quantity" of API in the tablet, this means 60-80% or more, so little space remains to the excipients. Try to granulate the API in a fluid bed, choosing the solvent and binder in such a way to not alter the API (say, if API strongly hydrophilic choose a lipophilic solvent and a binder soluble in it and not able to form complexes with the API). Then put the granulate with a suitable sugar excipient (isomalt is good) to get the required hardness, Mg Stearate 1,5-3% as a lubricant, fumed silica 1-3% as a disgregant. This should give you a tablet with hardness about 8 to Monsanto; disgregation time has to be determined experimentally (this can lead to some modification if a specific disgregation time is required).
I think two steps granulation might be suitable in your case.
First, try slugging.
Then, try wet granulation by fuild bed granulator.
Calcium Carbonate exhibits brittle fracture and looses its compressibility upon multiple slugging / compaction cycles. Wet granulation with water will cause the ionization of carbonates and ultimately potency of API will be lost. The legacy process is granulating the Calcium Carbonate with cooked Starch Paste, wet mill, dry in tray drier, mill and finally lubricate with Stearic Acid and compress into tablets. (Cost effective-no need of hi-fi costly co-processed excipients) Starch can act as binder and disintegrant.
1. Use colloidal silicon dioxide extragranularly, will give higher hardness and solve friability issue For DC Method
2. Use slugging process For dry granulation method
3. Use dry binder (HPC)- For DC Method
4. Use Gelatin with starch paste will give excellent hardness For wet granulation method
5. Use lactose and MCC 101 intragranularly provide higher hardness For wet granulation method
6. Optimize Granules fine ratio
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