Dabigatran Etexilate (DE) is a potent, synthetic, non-peptide competitive, rapidly acting oral direct thrombin inhibitor (oral DTI). It is an anticoagulant medication which can be taken by mouth. It is used as an alternative to warfarin.
Dabigatran Etexilate (DE) is the oral pro-drug of the active moiety dabigatran (DAB) and does not possess anticoagulant activity. The pro-drug dabigatran etexilate is used in its salt form dabigatran etexilate mesilate (DEM). That specifically and reversibly inhibits thrombin, the final enzyme in the coagulation cascade. The granted indication is primary prevention of venous thromboembolism (VTE) in patients undergoing elective major orthopedic surgery (MOS). It is a direct thrombin inhibitor indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.
Additional information
| Percentage | 35%, 40% |
|---|---|
| Documentation Available: | DMF under compilation |
| Forms of PFI | Pellets (for capsules) |
Description
The Innovator: Dabigatran is sold under the brand name Pradaxa Capsule (Boehringer Ingelheim)
150 mg capsules with a light blue opaque cap imprinted in black with the Boehringer Ingelheim company symbol and a cream-colored opaque body imprinted in black with “R150”.
75 mg capsules with a cream-colored opaque cap imprinted in black with the Boehringer Ingelheim company symbol and a cream-colored opaque body imprinted in black with “R75”.
The 150 mg capsule for oral administration contains 172.95 mg dabigatran etexilate mesylate, which is equivalent to 150 mg of dabigatran etexilate, and the following inactive ingredients: acacia, dimethicone, hypromellose, hydroxypropyl cellulose, talc, and tartaric acid. The capsule shell is composed of carrageenan, FD&C Blue No. 2 (150 mg only), FD&C Yellow No. 6, hypromellose, potassium chloride, titanium dioxide, and black edible ink. The 75 mg capsule contains 86.48 mg dabigatran etexilate mesylate, equivalent to 75 mg dabigatran etexilate, and is otherwise similar to the 150 mg capsule.
The recommended dose is 220mg once daily taken as 2 capsules of 110mg. For patients with moderate renal impairment or aged above 75 years, the recommended dose is 150mg once daily taken as 2 capsules of 75mg.
MKPPL has developed Dabigatran pellets equivalent to innovator product (PRADAXA) using aqueous technology, by maintaining the crystalline integrity of the drug.
The formulation is based on the preparation of dispersion of drug in purified water and homogenization to reduce the particle size of active ingredient, to achieve the dissolution equivalent to innovator.
The particle size distribution is measured at solution preparation stage and after loading of the drug to the spheres.
Based on reviewing the product we have adapted the process of Fluid bed coating.
In case of Fluid bed coater, the solution of Dabigatran along with other ingredients like Sodium Lauryl sulphate, Povidone (k-30), hydroxy propyl methyl cellulose, talc is sprayed on Tartaric acid spheres.
Dissolution Study of Pellets is conducted by using following conditions;
- Apparatus: USP Type I
- Condition A: Basket for 75 mg
- Condition B: Basket with modified diameter of 24.5 mm for 150 mg
- Speed: 100 RPM
- Medium: 0.1N HCL (pH 2.0)
- Volume 900 ml
- Time: 30 minutes
Multimedia dissolution study is conducted for both innovator and the MKPPL product.
Based on the stability study data the expiry date of the product is 3 years from the date of manufacturing.
