Nordmark has the technology and know-how to manufacture a full range of solid dosage forms:

   • Granules
   • Tablets
   • Film-coated tablets
   • Sugar-coated tablets
   • Capsules (hard gelatin with a pellet filling)

Nordmark's specialty dosage forms are:

   • Microtablets
   • Effervescent tablets

Nordmark is a specialist manufacturer of vitamin/mineral preparations in lozenge and effervescent tablet formulations.

Microtabletting (ø 2 mm) is a specialist pharmaceutical technology which was developed by Nordmark more than 10 years ago and first used in the formulation of pancreatin-based finished medicinal products (Panzytrat®).

The special steel rams used for tabletting compress 19 microtablets at once and produce approximately 2 million microtablets per hour, which are then coated with an enteric film in a fluidized bed coater. The number of microtablets per capsule determines the dose strength (for example, 10 000 or 25 000 lipase units (PhEur).

 
This special pharmaceutical formulation was developed in response to the need for a reliable and effective pancreatin drug that would simulate physiological conditions as closely as possible in the delivery of enzymes to the target organ, taking due account of the transport and digestive processes in the gastrointestinal tract. When the capsules burst open, the microtablets are released to form digestive islets in the gastric chyme which pass through the pylorus portion by portion and release their enzymes in the duodenum.

The principles that underlie pancreatin microtablet technology are by all means applicable to other therapeutic indications and active principles. We use the same technology in the formulation of the iron(II) sulfate product Ceferro®, because iron(II) itself may be extremely poorly tolerated by the stomach precisely because of its efficacy.

The enteric coating prevents iron(II) from being released in the stomach and thus avoids the gastric side effects otherwise associated with iron formulations. Furthermore, distribution of the active drug substance in microtablets facilitates rapid release of the iron as soon as the duodenum has been reached.
A conventional tablet would have to travel a long distance down the intestinal tract before releasing its full active substance load.

This example shows that the use of microtablets (which can be coated for sustained release as well as pH adjustment) is feasible for the production of medicinal products containing other active substances where compartmentalization of small units of drug would produce efficacy and safety benefits.
Painkillers would for example be suitable candidates for microtabletting technology.

Microtablets have a defined and standardized active substance content (which distinguishes them from pellets) and are therefore suitable for highly individualized dosing, for example on a per kilogram of body weight basis for pediatric use.
And finally, microtabletting provides a means for reformulating conventional tablet/sugar-coated tablet products, which could provide a basis for an economically lucrative product repositioning with potential benefits in terms of communication strategies, competitive edge and patent situation.

 

 

Enteric coated microtablets

Microtablet production: We developed tabletting technology to enable the production of microtablets with a diameter of 2 mm on a commercial scale. Microtablets are also used in new-generation multiple-unit dosage forms. The advantage of microtablets is their precision which guarantees delivery of exactly the right dose. Microtablets meet all the requirements for single-unit dosage forms, including consistency of weight and content, and as such may also be taken one by one in the form of solid drops.

The microtablet cores are approximately 80% pancreatin. Standard pharmaceutical excipients are added in a direct tabletting process. The product is safe for use by subjects with lactose intolerance.

Like pellets, microtablets are coated in a solvent-free process with a polymethacrylic acid/ester-based dispersion film. Fluidized bed drying gives excellent drying properties at mild temperatures and is an ideal means of providing the protection the enzymes need. The microtablets have a thickness and diameter of approximately 2 mm and weigh approximately 7.7 mg.

The coating is acid-fast pursuant to PhEur (test for disintegration of tablets and capsules, 2.9.1.).
The lead enzyme lipase is used for characterizing active substance release.

Assay is done in accordance with PhEur specifications by basket and paddle method. The product is incubated at a pH below 6 for 60 minutes, then transferred to a buffer with a pH of 6 resulting in rapid enzyme release, with at least 50% of the labeled lipase activity being released within 30 minutes.

 

Typical quantities of fill are as shown below:

 

Capsules as multiple-unit dosage forms

Encapsulated pancreatin products offer many advantages to the consumer.
The capsule rapidly dissolves in the stomach and releases its contents. The multiple small pellets or film-coated microtablets contained in the capsule make for optimum distribution of the active substance in the stomach contents. The coating on the individual pellets or tablets prevents them from being dissolved in the stomach and ensures reliable active substance release later on in the duodenum.

The capsules are filled with great precision in a controlled process. Bulk microtablets or pellets are filled into capsules under pancreatin-specific climatic conditions in accordance with the customer's specific regulatory requirements.

The format parts relevant to filling are specially designed for filling bulk products of this particle size distribution. The special design allows precision filling of the capsules and at the same time minimizes damage to the coated products during the filling process. 100% weighing is performed as an additional check to ensure a correct quantity of fill.