The present work investigates the formulation and biopharmaceutical estimation of gastric floating drug delivery system (GFDDS) of propranolol HCl using semi-synthetic polymer carboxymethyl ethyl cellulose (CMEC) and a synthetic polymer polyethylene oxide (PEO). A central composite design was applied for optimization of polymer quantity (CMEC or PEO) and sodium bicarbonate concentration as independent variables. The dependent variables evaluated were: % of drug release at 1 hr (D1hr), % drug release at 3 hr (D3hr) and time taken for 95% of drug release (t95). Numerical optimization and graphical optimization were conducted to optimize the response variables. All observed responses of statistically optimized formulations were in high treaty with predicted values. Accelerated stability studies were conducted on the optimized formulations at 40 ± 2°C/75% ± 5% RH and confirm that formulations were stable. Optimized formulations were evaluated for in vivo buoyancy characterization in human volunteers and were found buoyant in gastric fluid. Gastric residence time was enhanced in the fed but not the fasted state. The optimized formulations and marketed formulation were administered to healthy human volunteers and evaluated for pharmacokinetic parameters. Mean residence time (MRT) was prolonged and AUC levels were increased for both optimized floating tablets when compared with marketed product. High relative bioavailability obtained with optimized gastric floating tablets compared to commercial formulation, indicated the improvement of bioavailability.
Mathematically, the human alimentary tract organs were simplified in the model structure as separate compartments with
pathways of transfer that are kinetically homogenous and equally distributed. The development of gastro-compartment
model follows the first order kinetics of differential equations to describe cadmium absorption, distribution and elimination
in the human digestive system. With the aid of in vitro DIN assay, an artificial gastric and gastrointestinal fluid were
prepared using water leach purification (WLP) residue as a sample that contained toxic metals cadmium. The Simulation,
Analysis and Modelling II (SAAM II) V2.1 software is employed to design models easily, simulate experiments quickly and
analyze data accurately. Based on the experimental inputs and fractional transfer rates parameter incorporated to the
gastro-compartment model, the concentration of cadmium against time profile curves were plotted as the model output.
The curve presented concentration of cadmium in both gastric and gastrointestinal fluid where initially absorption phase
(first hour) occurred followed by the distribution phase (second to third hours) and elimination process (third to fifth
hours). The concentration of cadmium obtained from the simulated model structures was in good agreement with the
fitted model predicted measurements as statistical t-test conducted showed the values were not significantly different.
Therefore, modeling approach with SAAM II software gave realistic and better estimation of cadmium dissolution into
the human gastrointestinal tract.