A Novel Lactose/MCC/L-HPC Triple-Based Co-Processed Excipients with Improved Tableting Performance Designed for Metoclopramide Orally Disintegrating Tablets

Abstract

New co-processed excipients comprising lactose (filler and sweetener), microcrystalline cellulose (MCC, filler), and low-substituted hydroxypropyl cellulose (L-HPC, disintegrant and binder) were developed via solvent evaporation for the preparation of metoclopramide orally disintegrating tablets (MCP ODTs). Single-factor and Box-Behnken experimental designs were employed to optimize the formulation. The optimized formulation ratios were water: MCC: lactose (g/g) = 17.26:2.79:4.54:1. The results demonstrated that particles formed by solvent evaporation had superior flowability and compressibility compared to the physical mixture. Tablets compressed with these co-processed excipients exhibited a significantly reduced disintegration time of less than 25 s and achieved complete dissolution within 5 min. Pharmacokinetic studies revealed that MCP ODTs significantly improved C_max, which was 1.60-fold higher compared to conventional tablets. In summary, the lactose/L-HPC/MCC triple-based co-processed excipients developed in this study are promising and could be successfully utilized in orally disintegrating and fast-release tablets.

Keywords: co-processed excipients; metoclopramide; orally disintegrating tablets; pharmacokinetics.

Figure 1

Schematic diagram of disintegrating equipment of disintegrating method.

Figure 2

3D response surface plot showing influence of co-processed excipients on (A) disintegrating time (1–3); (B) angle of repose (4–6); (C) Carr’s index (7–9). The interaction effects of X₁ and X₂ (1, 4, 7); the interaction effects of X₁ and X₃ (2, 5, 8); the interaction effects of X₂ and X₃ (3, 6, 9); and the desirability 3D plot (10) and contour plot (11) for (D) optimized formulation.

Figure 3

Tensile strength diagram of single excipients and co-processed excipients (a), and figure of critical relative humidity (b).

Figure 4

SEM images of different excipients. ((a): Lactose, bar = 50 μm; (b): MCC, bar = 50 μm; (c): L-HPC, bar = 50 μm; (d): physical mixture, bar = 100 μm; (e): co-processed excipient, bar = 100 μm).

Figure 5

Physical characterization of various excipients in IR spectrum (a), XRD spectrum (b), TGA (c), and DSC thermogram (d).

Figure 6

Release curves of MCP ODTs and metoclopramide tablets (n = 6).

Figure 7

Mean plasma concentration–time profile of metoclopramide after administration of 10 mg control tablets and MCP ODTs in 6 beagle dogs.