A three phase hollow fiber liquid-phase microextraction with in situ derivatization (in situ HF-LPME) followed by high-performance liquid chromatography-ultraviolet detection (HPLC-UV) method was developed for the trace determination of metformin hydrochloride (MH) in biological fluids. A new derivatization agent pentafluorobenzoyl chloride (PFBC) was used. Several parameters that affect the derivatization and extraction efficiency were studied and optimized (i.e., type of organic solvent, volume of NaOH (4M) and derivatization agent in the donor phase, acceptor phase (HCl) concentration, stirring speed, temperature, time and salt addition). Under the optimum conditions (organic solvent, dihexyl ether; volume of NaOH (4M) and derivatization agent (10mg PFBC in 1mL acetonitrile) in the donor phase, 600 and100μL, respectively; acceptor phase, 100mM HCl (10μL); stirring speed, 300rpm; extraction time, 30min; derivatization temperature, 70°C; without addition of salt) an enrichment factor of 210-fold was achieved. Good linearity was observed over the range of 1-1000ngmL(-1) (r(2)=0.9998). The limits of detection and quantitation were 0.56 and 1.68ngmL(-1), respectively. The proposed method has been applied for the determination of MH in biological fluids (plasma and urine) and water samples. Prior to the microextraction treatment of plasma samples, deproteinization step using acetonitrile was conducted. The proposed method is simple, rapid, sensitive and suitable for the determination of MH in a variety of samples.
This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl), using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP):xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. 153Sm2O3 was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time (Tmax) at which the maximum concentration of metformin HCl in the blood (Cmax) was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. Cmax and the half-life were found to be within an acceptable range. It is therefore concluded that MKP3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region.