Matrix tablets: the effect of hydroxypropyl methylcellulose/anhydrous dibasic calcium phosphate ratio on the release rate of a water-soluble drug through the gastrointestinal tract I. In vitro tests

Abstract

Different hydroxypropyl methylcellulose (HPMC)/anhydrous dibasic calcium phosphate (ADCP) matrix tablets have been developed aiming to evaluate the influence of both components ratio in the control release of a water-soluble drug (theophylline). In order to characterise the matrix tablets, swelling, buoyancy and dissolution studies have been carried out in different aqueous media (demineralised water, progressive pH medium, simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid). The HPMC/ADCP ratio has turned out to be the determinant in the matrix behaviour: the HPMC characteristic swelling behaviour was modulated, in some cases, by the ADCP characteristic acidic dissolution. When the HPMC/ADCP ratio was ≥0.69, buoyancy, continuous swelling and low theophylline dissolution rate from the matrices (H1, H2 and H3) were observed in all dissolution media. Consequently, these formulations could be adequate as gastro-retentive drug delivery systems. Additionally, HPMC/ADCP ratio ≤0.11 (H5 and H6) induces a pH-dependent drug release which could be applied to design control drug release enteric formulations (with a suitable enteric coating). Finally, a HPMC/ADCP ratio between 0.11 and 0.69 (H4) yield a gastrointestinal controlled drug release, due to its time-dependent buoyancy (7 h) and a total drug delivery in 17 h in simulated colonic fluid.

Fig. 1

Evolution of H1–H6 and C matrices aspect after immersion in different media: demineralised water (a), progressive pH medium (b), SGF (c) and SIF (d) after 2, 4, 8 and 24 h

Fig. 2

Dissolution profiles of H1 (squares), H2 (circles), H3 (triangles), H4 (diamonds), H5 (plus sign), H6 (minus sign) and C (asterisks) matrices in different media: demineralised water (a) and progressive pH medium (b). Error bars represent the standard deviation (in some cases, they are smaller than the symbol size)

Fig. 3

Dissolution profiles from H1 (squares), H2 (circles), H3 (triangles), H4 (diamonds), H5 (plus sign), H6 (minus sign) and C (asterisks) matrices in different media: SGF (a), SIF (b) and SCF (c). Error bars represent the standard deviation (in some cases, they are smaller than the symbol size)