Innovative dosage forms for systematic drug delivery
Only correct formulation can turn a new active substance into a safe, ready-to-use drug that can be dosed as required. Formulation scientists ensure that the substance can be absorbed by the body and the therapeutic dose reaches the targeted organ. Not every active substance is suitable for ingestion as a tablet, and special demands on the form of administration – injection into the eye, products for inhalation, or orodispersible tablets that dissolve quickly in the patient's mouth without water – regularly create new challenges for formulation scientists. At Bayer, innovative pharmaceutical technologies often come into play in this context. Here are three examples.
Polymers for continuous sustained release
Polymer technologies are used in various fields today to ensure the targeted delivery of a drug in the desired dose. One example is a tablet with a perforated coating which releases the active ingredient continuously for 24 hours, thus saving the patient having to repeatedly take tablets.
During the production process, a hole of a precisely defined size (diameter = 0.3 mm) is burned with a laser into the coating, which is a water-permeable, but not water-soluble polymer membrane. The tablet's core is divided into two layers, one containing the active ingredient, the other a swelling agent. Once inside the gastrointestinal tract, the tablet absorbs water, which dissolves the active ingredient and causes the tablet to swell. This generates osmotic pressure inside the tablet, with the result that the dissolved active substance is continuously released at a constant rate through the hole in the coating.
Bayer also uses polymers to deliver active ingredients directly into the uterus, as in the case of intrauterine systems (IUS). In this field, continuous drug delivery can be maintained for as long as five years. Here, the active ingredient is embedded in a polymer matrix. This is in turn enclosed by a layer of silicone (polysiloxane), whose specific permeability guarantees the uniform release of the active substance.
Solution for poorly soluble drugs
Another application for polymers in drug formulation is dosage forms for active substances whose crystals are only slightly soluble in water. Without special processing, such active ingredients would be excreted by the body unchanged without having any effect – rather like ingesting sand.
Modern techniques make it possible to embed these substances in water-soluble polymers. In this process the insoluble crystals are split up, giving the molecules an 'amorphous' arrangement with no fixed structure. The researchers can now conserve the 'amorphous' arrangement of the active-substance molecules with the help of polymers. This 'solid solution' of active ingredient and polymer dissolves in water (and digestive juices) much more easily than the crystals of active substance alone. In many cases, this also leads to a temporary increase in the concentration of dissolved drug molecules, which can now be absorbed from the intestine into the bloodstream.
Solutions for protein therapeutics
Active substances that are based on proteins, known as biologics or biopharmaceuticals, place special demands on formulation scientists. If such substances were administered orally, they would be broken down by the digestive juices in the gastrointestinal tract before they could enter the bloodstream and reach the targeted site of action. They are therefore administered parenterally, i.e. by injection into a vein or subcutaneously (under the skin). In order to be injected, the active substance must be available in solution. At the same time it must be possible to store a drug over a relatively long period of time if it is to be usable in practice. However, if the biopharmaceutical is formulated in a ready-to-use solution, there is a risk that the protein molecules will agglomerate (clump together) during prolonged storage and lose their effectiveness. In this case the formulation scientists face the challenge of reconciling the need to preserve efficacy with the requirements of a long shelf life.
In many cases, however, this challenge can be solved using the technique of freeze-drying. After this gentle method of drying, the protein molecules often remain stable for at least six months; the active ingredient is then dissolved shortly before injection in the application solution, e.g. in a prefilled syringe.