Preparation of Coated Valproic Acid and Sodium Valproate Sustained-release Matrix Tablets

Abstract

The aim of this research was to investigate the technique for preparation of coated valproic acid and sodium valproate sustained-release matrix tablets. Different diluents were tested and selected as the effective absorbent for oily valproic acid. Effect of the amount of absorbent and hydroxypropylmethylcellulose on drug release from valproic acid-sodium valproate matrix tablets prepared with wet granulation technique was evaluated in pH change system. Colloidal silicon dioxide effectively adsorbed liquid valproic acid during wet granulation and granule preparation. The amounts of colloidal silicon dioxide and hydroxypropylmethylcellulose employed in tablet formulations affected drug release from the tablets. The drug release was prominently sustained for over 12 h using hydroxypropylmethylcellulose-based hydrophilic matrix system. The mechanism of drug release through the matrix polymer was a diffusion control. The drug release profile of the developed matrix tablet was similar to Depakine Chrono(®), providing the values of similarity factor (f2) and difference factor (f1) of 85.56 and 2.37, respectively. Eudragit(®) L 30 D-55 was used as effective subcoating material for core matrix tablets before over coating with hydroxypropylmethylcellulose film with organic base solvent. Drug release profile of coated matrix tablet was almost similar to that of Depakine Chrono(®).

Keywords: Coated matrix; preparation technique; sodium valproate; sustained-release; valproic acid.

Fig. 1

Comparative dissolution profiles. Comparative dissolution profiles of drug released from ‐‐♦‐‐ SR1; ‐‐■‐‐ SR2; ‐‐▲‐‐ SR3; ‐‐×‐‐ SR4; ‐‐×‐‐ SR4; ‐‐*‐‐ SR5; ‐‐■‐‐ Depakine ChronoR in phosphate buffer pH 6.2 (n=3)

Fig. 2

Comparative dissolution profiles. Comparative dissolution profiles of drug released from ‐‐‐‐ SR2; ‐‐♦‐‐ SR6; ‐‐●‐‐ SR7; ‐‐●‐‐ SR8; ‐‐*‐‐ SR9; ‐‐■‐‐ SR10; ‐‐+‐‐ SR11; ‐‐◊‐‐ SR12; ‐‐○‐‐ Depakine Chrono^® in phosphate buffer pH 6.2 (n=3)

Fig. 3

Photograph of scale-up SR 10 matrix tablet. Photograph of scale-up SR 10 matrix tablet after coated with: (a) HPMC-based film; (b) Eudragit^® L 30 D-55 subcoating film and (c) Eudragit^® L 30 D-55 subcoating film and over coated with HPMCbased film for 2 h at magnification of 10

Fig. 4

Scanning electron micrographs. Scanning electron micrographs of scale-up SR 10 matrix tablet surface morphology (50X) (a) the core tablet; (b) the cratering defect on matrix tablet after coated with HPMC film; (c) Eudragit^® L 30 D-55 subcoating film; (d) Eudragit^® L 30 D 55 film and over coated with HPMC-based film and (e) Depakine Chrono^® at magnification of 50

Fig. 5

Scanning electron micrographs. Scanning electron micrographs of cross-section of scale-up SR 10 matrix tablets after different coating (100X) (a) Eudragit^® L 30 D-55 subcoating film; (b) Eudragit^® L 30 D-55 and over coated with HPMCbased film for 1 h; (c) 2 h; (d) 3 h; (e) 4 h and (f) Depakine Chrono^® at the magnification of 100

Fig. 6

Comparative drug dissolution profile. Comparative drug dissolution profile of ‐‐■‐‐ scale up SR 3; ‐‐▲‐‐ scale up SR 3 after subcoat; scale up SR 3 after film coating for ‐‐×‐‐ 1 h; ‐‐◊‐‐ 2h; …×…. 3h; ‐‐♦‐‐ 4h and ….♦…. Depakine Chrono^® in phosphate buffer pH 6.2 (n=3)

Fig. 7

Comparative drug dissolution profile. Comparative drug dissolution profile of ‐‐■‐‐ scale up SR 10; ‐‐▲‐‐ scale up SR 10 after subcoat; scale up SR 10 after film coating for ‐‐×‐‐ 1 h; ‐‐◊‐‐ 2h; …×…. 3h; ‐‐♦‐‐ 4h and ….♦…. Depakine Chrono^® in phosphate buffer pH 6.2 (n=3)