Gamma scintigraphic study of the hydrodynamically balanced matrix tablets of Metformin HCl in rabbits

Abstract

The purpose of this study is to evaluate the in vitro and in vivo performance of gastro-retentive matrix tablets having Metformin HCl as model drug and combination of natural polymers. A total of 16 formulations were prepared by a wet granulation method using xanthan, tamarind seed powder, tamarind kernel powder and salep as the gel-forming agents and sodium bicarbonate as a gas-forming agent. All the formulations were evaluated for compendial and non-compendial tests and in vitro study was carried out on a USP-II dissolution apparatus at a paddle speed of 50 rpm. MOX2 formulation, composed of salep and xanthan in the ratio of 4:1 with 96.9% release, was considered as the optimum formulation with more than 90% release in 12 hours and short floating lag time. In vivo study was carried out using gamma scintigraphy in New Zealand White rabbits, optimized formulation was incorporated with 10 mg of 153Sm for labeling MOX2 formulation. The radioactive samarium oxide was used as the marker to trace transit of the tablets in the gastrointestinal tract. The in vivo data also supported retention of MOX2 formulation in the gastric region for 12 hours and were different from the control formulation without a gas and gel forming agent. It was concluded that the prepared floating gastro-retentive matrix tablets had a sustained-release effect in vitro and in vivo, gamma scintigraphy played an important role in locating the oral transit and the drug-release pattern.

Gastroretentive behavior of orally administered radiolabeled tamarind seed formulations in rabbits validated by gamma scintigraphy

“…The MKP3 release at 1, 2, 4, 6, 8, 10, and 12 h was found to be 25%, 40.3%, 65.8%, 75.9%, 79.9%, 88.2%, and 97.4%, and for the control formulation the values were 55.2%, 80.3%, 85.0%, 88.5%, 91.5%, 94.8%, and 95.0%, respectively. The obtained in vivo gamma scintigraphy results were similar to those of previously published studies, and it confirmed and proved that using a gel-forming agent such as TKP could sustain the drug release and that tablets will remain in the stomach for longer period of the time with optimum release rate 34,36…”

“…Furthermore, gamma spectroscopy data confirmed that neutron activation of the tablets produced no unwanted radioactive by-products 34,36. The in vitro dissolution result of the optimal formulation (MKP3) was compared with the MKP3-Sm formulation which contained 152 Sm.…”

“…Among all the formulations, MKP3 was found to be the optimal formulation; it contained 60 mg of TKP and 40 mg of xanthan; the FLT of this formulation (MKP3) was found to be 18 s and >90% of the drug had been released in 12 h. These in vitro data are consistent with previously published results and demonstrated that the formulation containing TKP could provide superior control release compared to the formulation containing TSP. The rate of drug release was prolonged for a longer time due to better gel-forming ability of the TKP polymer 34,36. This formulation had the highest similarity factor (f2) with commercial formulation (65%).…”

Design and preparation of controlled floating gastroretentive delivery systems for enhanced fexofenadine hydrochloride oral bioavailability

“…Therefore, different tablet formulations consisting of single polymers of various viscosities and at a constant polymer : sodium bicarbonate ratio (5 : 1) were investigated as a preliminary step. The floating behaviour of gastroretentive effervescent floating tablets is mainly attributed to the gas generation resulting from the interaction of sodium bicarbonate with the acidic medium, and its entrapment within the polymeric matrix [15].…”

<p>Promising Swellable Floating Bupropion Tablets: Formulation, in vitro/in vivo Evaluation and Comparative Pharmacokinetic Study in Human Volunteers</p>

“…The formulations without xanthan in their composition (FT1 and FT2), were not successful in giving sufficient strength to achieve controlled drug release and reached about 90% release in 2 h. This finding indicates the gelforming ability and high viscosity of the strong matrix layer formed by xanthan that could lead to a reduction of the effective diffusion coefficient of the drug resulting in a decreased drug release into the dissolution medium. 33,34 The release pattern of formulations with the highest concentration of glucomannan was slower than the formulations with the highest concentration of TKP in the assumption that the concentration of other combining polymers was fixed. This is owing to the high viscosity and gel-forming ability of glucomannan that formed strong and viscous gel gradually.…”