Formulation and Optimization of Sustained-Release Diclofenac Microspheres for Orally Disintegrating Tablets.

Abstract

Introduction: Chronic musculoskeletal problems necessitate long-term symptomatic treatments. In such cases, diclofenac (D_fNa) is frequently prescribed. However, its demand for frequent administration might result in serious dose-dependent complications. Furthermore, most patients with these illnesses are elderly and may have difficulty swallowing. Such factors can contribute to patients' noncompliance. Therefore, this study aimed to develop a sustained-release orally disintegrating D_fNa tablet using locally accessible excipients.

Methods: D_fNa microspheres were prepared using the emulsion solvent evaporation technique. Several parameters, including drug-to-polymer ratio (DPR), stirring speed (SS), internal phase volume, and polyethylene glycol content, were explored for their effect on microsphere characteristics. Significant factors were then selected and further optimized to produce microspheres with desirable responses. Eventually, the optimized microspheres were compressed into orally disintegrating tablets with appropriate excipients through direct compression.

Results: Preliminary studies indicated that the DPR and SS significantly influenced the response variables. Consequently, their effects on the selected response variables (entrapment efficiency [EE] and Z) were further optimized. This optimization identified optimal conditions at a DPR of 1:1.41 and SS of 905.17 rpm with a predicted EE (69.44%) and Z (175.33 μm). Confirmation tests indicated that the experimental results are in agreement with the predicted values (a percentage error below 5%). Furthermore, the three confirmation batches showed no significant difference in their characteristics, indicating remarkable reproducibility. The microspheres exhibited a non-Fickian anomalous release mechanism, best described by the Higuchi model. All the orally disintegrating tablets prepared from the microspheres met the USP specifications. However, FT1 (compressed at 10 KN) showed a release profile and kinetics similar to those of the uncompressed microspheres. Therefore, it was selected as the best formulation of D_fNa in this study.

Conclusion: This study successfully formulated microsphere-based sustained-release orally disintegrating D_fNa tablets that sustained drug release for at least 12 h.