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A gastroretentive in situ oral gel containing metformin hydrochloride (Met HCl) was prepared based on sodium alginate (Sod ALG), calcium carbonate, and hydroxyethylcellulose (HEC). The optimal composition of the formulation was explored based on the design of experiments (DoE). First, a 32 full factorial design was used for formulation E1 to determine proper composition of Sod ALG and calcium carbonate. Second, a circumscribed central composite design was employed to add HEC as a thickening agent (formulation E2). The dissolution rates at 15, 30, 60, 120, and 240 min were used as responses. Partial least squares regression analysis indicated the effect of each component in delaying the release of Met HCl in the oral gel formulation. The optimized formulation E2-08 consisting of 1.88% Sod ALG, 0.63% HEC, and 1.00% calcium carbonate and two more formulations, E2-10 and E2-12 conformed to USP monograph for extended release. Other physicochemical properties, including floating lag time and duration, viscosity, and pH, measured for each batch and FT-IR spectrometry analysis showed no unexpected interaction between Met HCl and excipients. The current study suggests the potential use of a gastroretentive in situ oral gel for Met HCl helping patient compliance. This study highlights that a systematic approach based on DoE allows the formulation optimization. [ABSTRACT FROM AUTHOR]

Organic solvents are widely used in pharmaceutical and chemical industry for chromatographic separations. In recent years, subcritical water chromatography (SBWC) has shown ability in replacing hazardous organic solvents used in traditional high-performance liquid chromatography (HPLC). In this work, a pain killer--aspirin--and an antidiabetic drug--metformin HCl--were successfully separated on an XBridge C18 column using no organic solvents in the subcritical water chromatography mobile phase. Both traditional HPLC and subcritical water chromatography were used for comparison purposes. SBWC separation of metformin HCl and aspirin were achieved at 95 °C and 125 °C, respectively. The recovery for both active pharmaceutical ingredients (APIs) obtained by SBWC is 99% in comparing with the stated content of each drug. The relative standard deviation is less than 1% for SBWC assays developed in this work. This level of accuracy and precision achieved by SBWC is the same as that resulted by the traditional HPLC analysis. [ABSTRACT FROM AUTHOR]

A sustained-release non-effervescent floating matrix tablet was prepared using a simple and efficient direct compression of spray-dried granules containing metformin hydrochloride and cetyl alcohol with hydroxypropyl methylcellulose K15M (HPMC K15M). The design of experiments was employed to explore the optimal composition of the tablet. The similarity factor was employed to evaluate the equivalence in dissolution profiles between the test tablets and Glucophage XR as a reference. Bootstrap analysis was used to eliminate the formulations for which the dissolution profile was potentially inequivalent to that of the reference. The optimized tablet consisting of 150 mg of cetyl alcohol and 17% HPMC K15M showed a dissolution profile comparable with that of the reference with a similarity factor of 52.41, exhibited a floating lag time of less than 3 s in buffer media, remained floating for 24 h, and reduced the tablet weight by about 20% compared to that of the reference. The current study sheds light on the potential use of non-effervescent gastro-retentive extended-release tablets for high-dose drugs using a simple and efficient direct compression method, and as a potential alternative treatment for Glucophage XR. This study also highlights the importance of a systematic approach to formulation optimization and the evaluation of the dissolution profile. [ABSTRACT FROM AUTHOR]