Can i please know your excipients add ed to the formulation and method of granulation. Also may i know what conditions of temperature and RH did you expose the tablets for?

If you give those details i can explain still better.

The melting point is around 70 degrees celsius.

Hence the tablets should be stored at 15-30 degrees. The drug is hygroscopic and photolytic too.

Can there be an assessment of the type of polymer used as the binder, the water sorption and retention property of the polymer and other excipients, the efficacy of anti oxidant property of the ingredients used in the formulation especially during the moistening, granulation and also the extent of drying of granules.

Raja Rajeswari Kamisetti Dear Madam,

Thank you so much for your valuable reply. The excipients used are Lactose (25 mg), Starch (30 mg), Polyvinylpyrrolidone (K-30) (8 mg), Talcum (2 mg), Magnesium Stearate (3 mg), Colloidal Silicon Dioxide (2 mg), Sodium Starch Glycollate (22 mg) and Sodium Lauryl Sulphate (0.1 mg) with Ranitidine Hydrochloride being 150 mg.

The granulation is done by preparing Polyvinylpyrrolidone (K-30) in Isopropyl Alcohol and the moisture content is maintained below 3% upon drying. The tablets are stored below 30 C throughout its distribution chain.

Please provide you valuable suggestions on ways to rectify this issue.

John Ordu

Hi Sir,

Thank you so much for the response. The polymer used for binding is Polyvinylpyrrolidone (K-30). The drying is done to bring the moisture content below 3%. The excipients used are Lactose (25 mg), Starch (30 mg), Polyvinylpyrrolidone (K-30) (8 mg), Talcum (2 mg), Magnesium Stearate (3 mg), Colloidal Silicon Dioxide (2 mg), Sodium Starch Glycollate (22 mg) and Sodium Lauryl Sulphate (0.1 mg) with Ranitidine Hydrochloride being 150 mg.

Please provide your valuable suggestions. Thank you so much.

Consider reducing the RH to 22%, substitute the povidon with excipient like mannitol or materials of similar property then packaging material can be changed from PVC- alu foil to Alu-Alu packaging material.

Thank you.

Consider reducing the RH to 22%, substitute the povidon with excipient like mannitol or materials of similar property then packaging material can be changed from PVC- alu foil to Alu-Alu packaging material.

Thank you.

Here you go...

Firstly you can remove starch because already you are doing granulation using pvp.

Starch will be hygroscopic and softens the formulation. So you can replace it any other diluents like micro crystalline cellulose or SCMC etc possible if no chemical interactions exist between ( you can check by FTIR).

Secondly i would like to ask if you are planning to prepare ODT or FDT? By seeing that sodium starch glycollate in your formula i got this...

I suggest you go for direct compression.

Then you will not encounter with moisture problems.

Also store in vacuum dessicator for further use.

Raja Rajeswari Kamisetti

Dear Madam,

Thank you so much for you insightful recommendations. We will try without starch as per your recommendation. Actually it is conventional tablet, and not ODT. I hope to get future recommendations as well. Thank you so much.

John Ordu

Hi John,

Thank you so much for you recommendations. We are using povidone for binding purpose during granulation. However, yes its good to add mannitol in the formulation and we shall try this one. The existing packaging is in strips. Thank you so much once again and I hope to get future assistance. Thank you.

Raja Rajeswari Kamisetti ,

Hello Ma'm,

In one of the tablet formulation of Cefpodoxime Proxetil, we accidently added Carboxymethyl Cellulose Sodium instead of Carboxymethyl Cellulose Calcium. This has led to failure in disintegration test. We have even taken a trial to dilute the Carboxymethyl Cellulose Sodium up to 300%, but still a viscous layer forms on the tablet outer and this prevents wetting of the tablet inner layers thereby increasing disintegration time beyond limit. We have added Carboxymethyl Cellulose Calcium, Crospovidone, Sodium Starch Glycollate and Starch in different proportion, but still it fails disintegration test. Would you please suggest If there are any alternatives. Thank you so much.

Dear Samrat,

1. Use those excipients which are having low % of moisture i.e. PGS in place of starch.

2. Use Dry granulation or Direct compression method of of tableting.

3. Remove Starch it contains 10-20% of moisture and absorb moisture make tablet soften during stability.

4. Use PVA based coating material as a moisture barrier

5. You can use a better packing material like Alu-Alu for better moisture protection

Hi Samrat

Probably by using various excipients you already tried the best alternatives.

Now i also suggest to change the granulation method. I mean switch from wet granulation to dry or slugging method. Or you can even try directly compressible excipients, as they are designed with limited or controlled moisture content and still very stable substances.

Also i think you should check with the packaging material.. I suggest ALU-ALU type of packing material.

Thank you

Raja Rajeswari Kamisetti

Thank you so much for your recommendations. It will be helpful. Thank you.

Deepak Chandra Sharma

Thank you so much for your recommendations. It will be helpful. Thank you.