6-Design, characterization and in vivo evaluation of modified release baclofen floating coated beads (copy)

Introduction

  • Baclofen: A centrally acting skeletal muscle relaxant used for treating muscle spasticity.

  • Issues with Immediate-Release: Rapid absorption linked to side effects, mainly orthostatic hypotension.

  • Study Objective: Develop modified release floating beads of baclofen to minimize side effects.

Preparation of Floating Beads

  • Materials: Alginate and gas-forming agents (calcium carbonate).

  • Coating: Eudragit RS100, Eudragit L100, cetyl alcohol for controlled release.

  • Method: Ionotropic gelation—sodium alginate mixed in deionized water, drug and gas-former added, dropped in calcium chloride.

Characterization of Beads

Buoyancy Characteristics

  • Floating Lag Time (FLT): Time to float—effective when FLT ≤ 2 minutes.

  • Floating Time (FT): Duration beads float; successful formulations had FT > 12 hours.

Drug Entrapment Efficiency (DEE)

  • DEE was calculated based on drug retention in beads.

  • Factors Affecting DEE: Polymer concentration, drug-to-polymer ratio, GFA concentration, and coating type.

Scanning Electron Microscopy (SEM)

  • Surface morphology assessed pre- and post-coating. Uncoated beads: rough, porous; coated beads: smooth with no visible pores after prolonged coating.

Differential Scanning Calorimetry (DSC)

  • Thermal behavior of beads analyzed to confirm drug embedding.

In Vitro Release Studies

  • Comparison of release profiles: Uncoated vs. coated beads showed significantly retarded drug release with coating application.

  • Coating Types: Eudragit RS100 and L100 demonstrated the best retarding effects compared to cetyl alcohol.

In Vivo Studies

Pharmacokinetics

  • Evaluated using rabbit models. Key pharmacokinetic parameters:

    • Cmax (peak plasma concentration): B1-RS15 < Baclofen.

    • Tmax (time to peak concentration) significantly prolonged for B1-RS15.

    • AUC (area under the curve) increased for modified release formulation.

Blood Pressure Measurements

  • Assessed hypotensive effects post-administration of Baclofen and B1-RS15.

  • Results: B1-RS15 showed a reduced incidence of hypotension compared to Baclofen tablets, maintaining near-normal blood pressure values.

Storage Stability

  • Effects of storage on drug content and release profile were negligible after 12 months, indicating good stability.

Conclusion

  • B1-RS15 formulation demonstrates potential for improved oral bioavailability and reduced side effects from baclofen. Minimal side effects observed, especially in relation to hypotension.

  • Future Work: Further optimization studies and clinical evaluations needed.