New Method of Controlled Drug Release

Researchers in Oxford University’s Inorganic Chemistry Laboratory have found that they can intercalate a range of pharmaceutically active molecules between the layers of a layered inorganic host.

While working on the ion-exchange abilities of a family of inorganic materials known as Layered Double Hydroxides (LDHs), researchers have recognised that many commonly prescribed drugs and other over-the-counter medicines are either anions or can be conveniently and reversibly converted into an anion form. Research revealed that addition of one of these LDHs to a solution of a chosen pharmaceutical in water at room temperature results in intercalation of the these molecules between the sheets of the host structure. The LDHs are able to swell by up to 20Å to accommodate the size of the new guest molecules.

Certain drugs require controlled release and/or amelioration of side effects. LDHs already have medicinal properties in their own right as antacid and antipepsin agents. Propriety antacids products such as Talcid™ and Altacite™ contain the LDH [Mg6Al2(OH)16]CO3.

To date, the researchers have shown that compounds such Diclofenac, Ibuprofen, Naproxen, and Gemfibrozil intercalate rapidly into LDHs. The researchers are then able to quantitatively recover these molecules on demand. At the moment, drug release can be achieved by either dissolving the entire drug/LDH composite in dilute acid or by adding the drug/LDH to a phosphate buffer at pH 7. Preliminary kinetics experiments using phosphate buffers show that these drugs can be released back into solution in 1-3 hours at 37 °C.

Apart from the potential of using these materials to deliver drugs in vivo, the host itself could have additional benefits. It will be possible to control the point of release and pharmokinetic profile by selection of the metals ions in the host layers. The antacid performance and pH stability is also controllable by the choice of metal ions in the host layers. Confinement of the drugs between the metal’s layers restricts molecular interactions and dynamics and should improve long-term stability. Improved taste qualities of the formulation are also predicted.

Isis Innovation, Oxford University’s technology transfer company, has filed a UK priority patent application for this technology and welcomes contact from potential commercial partners.

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