How to prepare stable Raberazole, pantoprazole, omeprazole formulation?

In recent days, we have found that, some of proton pump inhibitors failed and has been removed from Nepali market by Department of drug administration. It has been said that the formulation from reputed companies failed in some pharmacopieal test.

 So lets us discuss on some facts about PPIs.

Proton pump inhibitors are widely used products in most of the prescription in Nepal. Some of the examples of PPIs are omeprazole, lansoprazole, rabeprazole, esomeprazole, pantoprazole, pariprazole, and leminoprazole. These are basically benzimidazole derivatives with different substitution in branch chain. These molecules are highly susceptible against acid and the degradation of such molecule in presence of acid .

Let us take example of Rabeprazole sodium, which is available in enteric coated tablets of 10mg and 20mg strength. Here the tablets use inactive ingredients as Light Magnesium Oxide, Mannitol, Croscarmellose Sodium, Hydroxypropyl Cellulose, Microcrystalline Cellulose, Magnesium Stearate, Purified Talc, Hypromellose (HPMC 5 CPS), P.E.G 6000, acrylic coating systems.

Here, inactive ingredients need to be chosen carefully, with higher pH. Generally most of the pharma companies uses acrylic coating system, which is inherently acidic in nature. The acid nature of polymer cause degradation to the active molecule of tablets in long run so it need to be protected. It is suggested that, a protective primary protective coating is necessary for tablets before acrylic coating.

Generally, HPMC, ethyl cellulose and phthalate are used for primary enteric coating of tablets and latter Enteric coating. This will help the product to pass the pharmacopieal test of the product.

Dissolution parameters can be (Note: dissolution media and parameters can be different if other differentiating media is used, but it should be first acid media and second buffer/basic media at higher pH):

Acid Stage:

Apparatus: USP II, Paddle

Medium: 0.1M Hcl

Volume: 700ml

Speed: 75-100 rpm

Time: 2.0 hrs

Temp: 37 C

Limit: NMT 10% released

Buffer Stage:

Apparatus: USP II, Paddle

Medium: pH 9.0 Borate buffer

Volume: 1000ml

Speed: 75-100 rpm

Time: 45 minutes (time points, 10, 15, 20, 30, 45 mins)

Temp: 37 C

Limit: NLT 95% released

 It was said that the Drug regulatory bodies couldn't get proper results, this can happen, as the molecule is not stable in lower pH and there is high chance of degradation, some stabilizer need to be added or dissolution is done in higher pH. 

For more discussion, kindly contact us for any of the Benzimidazole derivatives products.
Follow our facebook page as well.

If you have any queries, kindly put your question here.