Micropump description

Micropump Platform Description

Micropump® is a controlled-release delivery system which permits either extended, or both delayed and extended, delivery of small chemical drugs. It is particularly suitable for drugs with a narrow window of absorption in the upper part of the small intestine.

  • More than 70% of chemical drugs are absorbed almost exclusively in the small intestine, with a transit time duration limited to 3 to 4 hours. In order to extend the time of action of these drugs, it is necessary to increase the duration of absorption by maintaining the drugs longer in the stomach or in the small intestine.

Unlike gastric-retention tablets, which are usually not authorized to treat children and may be unsuitable for use by certain elderly patients, the exceptionally small size of Micropump microparticles allows formulation of suspensions/syrups (or sachets) for children and for elderly patients (LiquiTime™).

Micropump consists of a multiple-dose system containing 5,000 to 10,000 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, operating as a miniature delivery system, releases the drug by osmotic pressure at an adjustable rate and over an extended period of time.

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 microparticles’ design can be adapted to each drug’s specific characteristics by modifying the coating thickness and composition (including the excipients encapsulated with the drug) for improved efficacy (i.e., extending therapeutic coverage), reduced toxicity and/or side effects (i.e., reduced Cmax or peak drug concentration in the plasma) and improved patient compliance (once-a-day regimen). Such adaptations are particularly useful in the context of chronotherapy.

Since the drug is entirely enclosed in each microparticle, Micropump offers taste masking and tamper-resistant advantages (Trigger Lock™).

Micropump Platform Performance

  • 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.

Micropump Platform Advantages

  • Marketed and approved platform: FDA-approved product (Coreg CR®, a controlled release formulation of carvedilol phosphate, manufactured by Flamel and marketed by GlaxoSmithKline in the USA) and one product approved in some European countries (Micropump aspirin, a controlled-release formulation of aspirin in co-development in the USA with New Haven Pharmaceuticals as NHP-554);
  • Versatile formulation to serve all market applications including pediatric and geriatric patients:
    • Sachets (easy to swallow due to the microparticles’ size);
    • Capsules; and
    • Tablets.
  • Taste masking properties;
  • Good tolerability;
  • Avoids dose dumping;
  • Reduces intra- and inter-variability;
  • Allows combination of different drugs whose release can be controlled separately;
  • Easy to scale up to industrial high-volume production (based on fluidized bed spray coating and granulation);
  • Cost effective manufacturing process; and,
  • Strong intellectual property position.

In addition, Micropump has proven competitive advantages for new pharmaceutical applications:

  • LiquiTime™ allows the extended release liquid formulations of drugs for patients who have difficulty swallowing tablets or capsules, such as children and the elderly.
  • Trigger Lock™ allows the tamper-resistant controlled release formulations of narcotics and other drugs susceptible to abuse. 

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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).
Link to the document

Micropump aspirin

A Micropump-based controlled-release formulation of acetylsalicylic acid (“ASA”), or aspirin, has been approved in some European countries for the prophylaxis against myocardial infarction, stroke and vascular death. The product represents the world’s only proprietary, once-daily oral 24-hour controlled-release aspirin.

Micropump aspirin is being co-developed with New Haven Pharmaceuticals as NHP-554.
The drug is being developed as tour programs for the following indications: secondary prevention of stroke and cardiovascular events, arthritis, foreign body reaction, and liver injury in HCV patients.