Matrix tablets based on amino acid-derived polyesteramide containing release modifiers


The aim of this study was to develop controlled-release matrix tablets of ketoprofen (K) and dexketoprofen trometamol (DK-T), investigating a new application of the polymer poly (L-alanine-dodecanediol-L-alanine-sebacic) (PADAS). The influence on drug release of the type of filler (lactose, mannitol, microcrystalline cellulose or dibasic calcium phosphate) and of the polymer/filler proportion was also investigated.

Evaluation of the flow properties of these materials (to facilitate a rational design of prolonged release formulation) showed this polymer to have good flowability. The compatibility between the formulation components was also investigated, by differential scanning calorimetry, and no drug-excipient interaction was detected.

The dissolution study showed that PADAS is capable of forming inert matrix tablets with ketoprofen, and that drug retention within the matrix increases in line with the polymer proportion. Lactose and mannitol both promoted ketoprofen diffusion by forming channels in the matrix structure. Microcrystalline cellulose generated an axial expansion of tablets, which promoted drug release. Dibasic calcium phosphate retained ketoprofen, acting as an excipient for prolonged drug release. All tablets with ketoprofen behaved as inert matrix tablets, controlling drug release mainly by diffusion. However, the polymer did not retain dexketoprofen trometamol in the matrix, and so it presented a conventional dosage release form.