Prolonged-release minitablets with carbamazepine - preliminary observations in vitro.

Objective: The aim was to develop prolonged-release minitablets (MT) with carbamazepine (CBZ).

Methods: Matrix-type 3-mm MT (5 mg CBZ) were prepared by direct compression using hydrophilic (hypromellose) or hydrophobic polymers (ethylcellulose, Kollidon SR, glyceryl behenate). Coated prolonged-release MT (2.5 mm/3 mg of CBZ) were produced using ethylcellulose or Eudragit RL/RS. The release tests were performed in a basket apparatus with water or 1% sodium lauryl sulphate solution as dissolution media.

Key Findings: High-viscosity hypromellose used as a matrix polymer resulted in slow release of CBZ (80% released during 12 h). Dissolution was slower from hydrophobic matrices. Non-swelling MT cores were successfully coated with Eudragit RL/RS, which resulted in the prolonged release of CBZ (80%/14 h), depending on the film thickness and Eudragit composition. Careful choice of pore formers in the coating film allowed to reduce lag time. Ethylcellulose was unsuitable as coating polymer due to low permeability to CBZ and unsatisfying mechanical resistance of the films modified with hypromellose.

Conclusion: Prolonged release of CBZ was obtained from both matrix-type and coated MT. Further development of MT as a single unit or multicompartment prolonged-release new dosage form especially suitable for children has been justified.