Controlled Release of Oral Drugs

Micropump® (PDF file) is designed for the extended (and/or delayed) release of small chemical drugs via oral administration. It may be used to develop extremely precise pharmacokinetic profiles of single or combination of drugs, in a variety of formats (pill, tablet, capsule, sachet, or liquid). It is particularly suitable for drugs with a narrow window of absorption in the upper part of the small intestine.

Micropump consists of a multiple-dose system containing 5,000 to 50,000 microparticles per capsule or tablet. The 100-500 microns diameter-sized microparticles are released in the stomach and pass into the small intestine, where each microparticle operates as a miniature delivery system. Micropump microparticles allow an extended transit time in the small intestine with a mean plasma residence time extended up to 24 hours, which is especially suitable for short-lived drugs known to be absorbed only in the small intestine.

Micropump’s Key Attributes

  • Permits the extended delivery (up to 24 hours) of chemical drugs with a narrow window of absorption, or, both delayed and extended delivery of these drugs (up to 12 hours following the drug uptake and for a release over an additional 12 hours);
  • Allows the controlled-release of poorly soluble (< 0.01mg/L) as well as highly soluble (> 500g/L) chemical drugs; and,
  • Applicable to low dose (below 4 mg) or high dose (1,000 mg) chemical drugs.
  • Good tolerability;
  • Avoids dose dumping;
  • Reduces intra- and inter-variability.

Coreg CR®

Coreg CR, a Micropump-based controlled-release formulation of carvedilol phosphate, was launched in the USA in 2007 by Flamel’s partner, GlaxoSmithKline.

Coreg CR is an alpha/beta-adrenergic blocking agent indicated for the treatment of mild to severe chronic heart failure, left ventricular dysfunction following myocardial infarction in clinically stable patients, and hypertension.

Coreg CR is composed of immediate release microparticles and controlled/delayed microparticles, each with a different release profile, to affect a once-daily dose, with the same peak to through concentrations and Cmin than the IR (Immediate Release) Coreg given twice a day.

Coreg CR is manufactured exclusively by Flamel Technologies at its FDA-approved manufacturing facility (Pessac, France).

On October 15, 2010, the FDA issued a response letter to Flamel Technologies’ citizen petition filed on April 19, 2010, regarding Coreg (carvedilol phosphate) extended release capsules (FDA-2010-P-0216).

The issuance in January 2012 of the US 209’ patent (No. 8,101,209; “Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles”) and its registration in the Orange Book by our partner GlaxoSmithKline may strengthen the ability to defend Coreg CR against generic competition in the future.
Coreg CR is registered trademark of GlaxoSmithKline