Formulation, in vitro evaluation and study of variables on tri-layered gastro-retentive delivery system of diltiazem HCl

Abstract

Context: Tri-layered floating tablets using only one grade of polyethylene oxide (PEO) would enable easy manufacturing, reproducibility and controlled release for highly soluble drugs.

Objective: To evaluate the potential of PEO as a sole polymer for the controlled release and to study the effect of formulation variables on release and gastric retention of highly soluble Diltiazem hydrochloride (DTZ).

Methods: Tablets were compressed with middle layer consisting of drug and polymer while outer layers consisted of polymer with sodium bicarbonate. Design of formulation to obtain 12 h, zero-order release and rapid floatation was done by varying the grades, quantity of PEO and sodium bicarbonate. Dissolution data were fitted in drug release models and swelling/erosion studies were undertaken to verify the drug release mechanism. Effect of formulation variables and tablet surface morphology using scanning electron microscopy were studied.

Results and discussion: The optimized formula passed the criteria of USP dissolution test I and exhibited floating lag-time of 3–4 min. Drug release was faster from low molecular weight (MW) PEO as compared to high MW. With an increase in the amount of sodium bicarbonate, faster buoyancy was achieved due to the increased CO₂ gas formation. Drug release followed zero-order and gave a good fit to the Korsmeyer–Peppas model, which suggested that drug release was due to diffusion through polymer swelling.

Conclusion: Zero-order, controlled release profile with the desired buoyancy can be achieved by using optimum formula quantities of sodium bicarbonate and polymer. The tri-layered system shows promising delivery of DTZ, and possibly other water-soluble drugs.

• Diltiazem HCl
• floating lag time
• gastro-retentive
• polyethylene oxide
• tri-layered
• zero-order