DELHI, India and GENEVA, June 19,
2018 /PRNewswire/ --
- New patented production process solves stability issues of drug
API Digoxin Micronized.
- COS (CEP) awarded by EDQM.
- Patent application filed for innovative process.
- Optimum particle size distribution (PSD) achieved for digoxin
formulation homogeneity, dissolution and bioavailability.
Alchem International Private Limited ("Alchem") , a privately
held pharmaceutical company focusing on the production of plant
derived active pharmaceutical ingredients, today announced the
award of European Certificate of Suitability (COS) by European
Directorate for the Quality of Medicines ( EDQM) for its innovative
manufacturing process for micronized Digoxin overcoming stability,
regulatory and formulation issues for generic manufacturers of
digoxin tablets.
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)
Speaking from Alchem's European offices in Geneva (Switzerland) Raman
Mehta, Alchem CEO and President, commented, "Whilst generic
formulations of digoxin compared to the originator product Lanoxin
have had to compromise to date on bioavailability and dissolution
due to stability issues with micronized digoxin the process
innovations of our R&D team have removed these
barriers." Raman Mehta continued, "Our customers are now able
to formulate digoxin at the optimum particle sized distribution
(PSD) with a molecule that is stable for transport and one
year at ambient temperatures (15 - 25 degrees Celsius) and 3 years
under cold storage (3 - 8 degrees Celsius). We fully expect
the shelf life to be extended to five years based on ongoing
stability studies providing a clear advantage for handling and
formulation."
Digoxin is a specialist drug administered either orally or
intravenously to treat various heart conditions including atrial
fibrillation, atrial flutter, and heart failure. Digoxin has a low
and narrow dosage range that is patient specific and must be
calculated depending on medical condition, age, weight, gender and
creatinine clearance.
As a result of this patient specific and low and narrow dosage
range (tablets normally contain only 62.5mcg per tablet) the
production of the oral dosage forms presents a particular challenge
to pharmaceutical manufacturers to achieve homogeneity, dissolution
and optimum bioavailability.
Specific research on digoxin formulation published in The
European Journal of Clinical
Pharmacology[1] supports that
particle size is an important determinant of the dissolution rate
and bioavailability of digoxin. The study demonstrated that the
bioavailability of digoxin in tablets with particle sizes of 7 mu
or 13 mu was 78-97% of that of digoxin in solution whilst tablets
with larger particle sizes show markedly lower bioavailability.
Tablets with the largest particle size (102 mu) were only 39%
bioavailable compared to the reference
solution[1],[2]
.
The importance of particle size is confirmed by the category
originator Lanoxin which utilizes a particle size distribution
(PSD) of 10 μ: NLT 85%, 20 μ: NLT 95%, 30 μ: NLT 99%. Whilst
post production micronization of digoxin can and has been employed
by some API manufacturers to attempt to mimic the specification it
cannot achieve the same PSD range and post production micronization
also compromises the stability of the active ingredient (API). In
addition, regulatory authorities - such as EDQM - do not accept
post production micronization on APIs if not fully described in the
API dossier (DMF) or COS (CEP) as it potentially changes the
structure, integrity and stability of active ingredients.
Alchem International have addressed these challenges by
revisiting the production process to achieve the target PSD in
stream, during the production process, rather than post production
to provide a stable molecule. The issuance of a COS (CEP) following
an assessment and GMP audit by EDQM demonstrates the new production
process' capability and robustness and the process is now subject
to a patent filing.
About Alchem International
Alchem International is a privately-owned company active
pharmaceutical ingredient (API) manufacturer and offers 18 DMF
dossiers with regulatory filings in over 20 countries worldwide.
Please visit: http://www.alcheminternational.com.
References.
- Eur J Clin Pharmacol. 1975 Jun 13;8(5):365-70. Effect of
particle size on the bioavailability of digoxin. Jounela AJ,
Pentikäinen PJ, Sothmann A.
- Br J Clin Pharmacol. 1978 May;5(5):465-7. The influence
of digoxin particle size on absorption of digoxin and the effect of
propantheline. B F Johnson, J O'Grady, and C Bye.