Preparation and evaluation of enteric coated tablets of hot-melt extruded lansoprazole

Abstract

The objective of this work was to use hot-melt extrusion (HME) technology to improve the physiochemical properties of lansoprazole (LNS) to prepare stable enteric coated LNS tablets. For the extrusion process, we chose Kollidon^® 12 PF (K12) polymeric matrix. Lutrol^® F 68 was selected as the plasticizer and magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10% drug load was extruded with K12 and F68. LNS changed to the amorphous phase and showed better release compared to that of the pure crystalline drug. Inclusion of MgO improved LNS extrudability and release and resulted in over 80% drug release in the buffer stage. Hot-melt extruded LNS was physically and chemically stable after 12 months of storage. Both formulations were studied for compatibility with Eudragit^® L100-55. The optimized formulation was compressed into a tablet followed by coating process utilizing a pan coater using L100-55 as an enteric coating polymer. In a two-step dissolution study, the release profile of the enteric coated LNS tablets in the acidic stage was less than 10% of the LNS, while that in the buffer stage was more than 80%. Drug content analysis revealed the LNS content to be 97%, indicating the chemical stability of the enteric coated tablet after storage for six months. HME, which has not been previously used for LNS, is a valuable technique to reduce processing time in the manufacture of enteric coated formulations of an acid-sensitive active pharmaceutical ingredient as compared to the existing methods.

Keywords: Lansoprazole; enteric coating; hot-melt extrusion; release; stability.

Figure 1

Modified screw design used for preparation of lansoprazole using hot-melt extrusion

Figure 2

DSC graphs of pure lansoprazole, F1 b (10% LNS- 30% F68- K12), and F2 (10% LNS- 4% MgO- 30% F68- K12)

Figure 3

Dissolution profiles of pure lansoprazole, F1 b (10% LNS- 30% F68- K12), F2 (10% LNS- 4% MgO- 30% F68- K12), and the core tablet in phosphate buffer (pH 6.8, 5 mM SLS)

Figure 4

FT-IR analysis of pure lansoprazole, physical mixtures (F1 b and F2), and the extrudates (F1 b and F2)

Figure 5

DSC graphs of F1 b (10% LNS- 30% F68- K12) and F2 (10% LNS- 4% MgO- 30% F68- K12) after 12 months of storage (25°C/60% RH) and pure lansoprazole

Figure 6

Dissolution profile of lansoprazole marketed formulation and lansoprazole enteric coated tablet before and after 6 months of storage (25°C/60% RH). The acid stage (0.1 N HCl) was the first 1 hour and the buffer stage (phosphate buffer, pH 6.8, 5 mM SLS) was the second hour.