For active pharmaceutical ingredients that are highly affected by temperature ( >25 c ) and humidity( > 50%RH ), what type of excipients are beneficial for protection from the effect of temperature and humidity?
Hi Elawni,
Filler or binder plays the major role, as its percentage of content is normally higher than others. Try to use spray dried lactose in this case. No need to be fastidious about lubricant, glidant or disintegrating agent. Most importantly, your lab should have sufficient capability to control the surrounding humidity level (here, below 50%RH) and not forget to use alu-alu blister finally.
1) Mannitol as the main filler. Mannitol is not hygroscopic and will avoid degradation by water absorption. Anhydrous calcium phosphate (Emcompress) is another option.
2) Colloidal silicon dioxide (Aerosil 200) mixed with the active. Aerosil will adsorb wáter avoiding contact with the sensitive API.
3) I think anhydrous lactose as a filler could help (spray dried lactose contains 5% hysdrated water, anhydrous lactose contains less tha 0.1%),
4) A coating of the solid dosage form by a non-containing water procedure could help to avoid the contact of the API with the environment.
5) Do not use excipients with high content of water such as corn starch (13%). Most of disintegrants has about 5% of water (croscarmellose, crospovidone) but sodium starch glycolate has more water, (I do not remembrer the specification) and must be avoided.
Addition of mannitol would lead to increase in hygroscopic nature of formulation.
It would be better to add lactose to protect from moisture and perform coating for protection from light sensitivity.
For heat sensitive drug it's better to develop a zero heat process.
No, mannitol is not hygroscopic. See the Handbook of Pharmaceutical Excipients page 424, Sixth Edition: ":
In pharmaceutical preparations it is primarily used as a diluent (10–90% w/w) in tablet formulations, where it is of particular value since it is not hygroscopic and may thus be used with moisture-sensitive active ingredients."
Its loss of drying is less than 0.3% You could be mistaken with sorbitol or maltitol.
For such type of API you have to use excipients that have low moisture content like Avicel PH 200 LM. Also use of some type of silica (to maintain the moisture content low) in the final formulation. However it all depend on how you are doing the granulation.
You have to choose Dry granulation (slugging and compression) OR Moist Granulation (moisture enough to make the powder compressible). However in moist granulation addition of liquid is a critical factor.
These are the possibilities you can opt for.
Hope this helps.
Best Regards
Shuaib
It's preferably to use co-processed excipients such as, Mannogem EZ (spray dried mannitol), Neosorb (spheronized sorbitol), Pharmaburst C1 (Mannitol, Sorbitol, Crosspovidone, Silicone Dioxide). Such excipients are multifunctional, have more than a pharmaceutical function in tablet formulation development. As for liquid and aqueous formulations, it's preferably to use Sorbitol as Humectant in concentration > 10%. Chelating agents such as EDTA/sodium edetate and adsorbents such as Mg/Al salts can also be used to adsorb drug molecules and prevent its degradation.
You can also use colloidal silicon dioxide (Aerosil) to protect and prevent moisture sensitivity.
There is no hard and fast rule. The question can be what kind of PROCESS instead of excipients for Moisture and Heat sensitive API's. Excipients are pharmacologically inactive but pharmaceutically active.
2 Important Controls
Environment (Dehumidification for Moisture Sensitive)
Process (Direct / Non-aqueous for Moisture Sensitive & Heat Sensitive)
For moisture and heat sensitive API,
1.Use low moisture content excipients.(eg. MCC PH 200, MCC PH 112, Anhydrous lactose)
2.Avoid adding those excipients which contains higher amount of moisture.(eg. Starch[12-18%], CCS, SSG)
3. Use colloidal silicon dioxide, magnesium aluminosilicate, for moisture adsorbent.
4.Use non-aqueous granulation, Slugging, DC method for tabletting.
5.Use moisture barrier coating material,seal coat (PVA).
6.Formulate the batch in low RH area.
7.Protect drug product using suitable packing material. (eg. Alu-Alu)
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