Design and optimization of a stomach-specific drug delivery system of repaglinide: application of simplex lattice design.

The current study involves the development of oral bioadhesive hydrophilic matrices of repaglinide and the optimization of their in vitro drug release and ex vivo bioadhesion. A simplex lattice design was employed to systematically optimize the drug delivery containing two polymers and a filler. The proportions of polyethylene oxide (PEO), microcrystalline cellulose (MCC) and lactose were varied to be fitted in simplex lattice design. Mucoadhesion (M), drug release at 2 h (Q2) and drug release at 8 h (Q8) were taken as responses. Response surface plots were drawn and the optimum formulation was selected by desirability function. The criteria for optimized formulation were set for mucoadhesion as maximum, Q2 as 20% and Q8 as 80%. The formulations were also checked for their swelling index and showed good swelling characteristic. In vitro drug release study was carried out using simulated gastric fluid (SGF) pH 1.2. The experimental values of M, Q2 and Q8 for check point batch were found to be 0.211N, 21.87% and 80.86% respectively. The release profile indicated anomalous (non-Fickian) transport mechanism. The optimized formulation was further checked for its compatibility with other excipients by studying FTIR and DSC studies and they indicated the absence of any significant chemical interaction within drug and excipients.

Design, characterization and in vitro evaluation of stavudine-loaded microspheres.

The aim of the present study was to prepare and evaluate microspheres of Eudragit containing an antiviral drug stavudine. Microspheres were prepared by O/O solvent evaporation method using acetone/liquid paraffin system. The prepared microspheres were characterized for their micromeretic properties and entrapment efficiency; as well by Fourier transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD) and scanning electron microscopy (SEM) which revealed the crystalline nature of drug in a final state. The in vitro studies revealed the controlled release of drug from microspheres up to 12 h and the best fit release kinetics was achieved with a Higuchi plot and found to be diffusion controlled. The yields of preparation and entrapment efficiencies were very high with a larger particle size for all the formulations. Mean particle size, entrapment efficiency and production yield were highly influenced by the type of polymer and polymer concentration.

Stomach-specific drug delivery of 5-fluorouracil using ethylcellulose floating microspheres.

A multiple-unit-type oral floating dosage form (FDF) of 5-Fluorouracil (5-FU) was developed to prolong gastric residence time for the treatment of stomach cancer. The floating microspheres were prepared by solvent evaporation method. The prepared microspheres were characterized for their micromeretic properties, floating behavior and entrapment efficiency; as well by Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), thin layer chromatography (TLC) and scanning electron microscopy (SEM). The in vitro release studies and floating behavior were performed in HCl buffer pH 1.2, Phosphate buffer pH 4.5 and in Simulated Gastric Fluid (SGF). The best fit release kinetics was achieved with Higuchi plot. The yields of preparation were very high and low entrapment efficiencies were noticed with larger particle size for all the formulations. Mean particle size, entrapment efficiency and production yield were highly influenced by polymer concentration. It was concluded from the present investigation that porous Ethylcellulose microspheres are promising controlled release as well as stomach targeted carriers for 5-FU.

Statistical Design of Experiments on Fabrication of Bilayer Tablet of Narrow Absorption Window Drug: Development and In vitro characterisation.

The current study involves the fabrication of oral bioadhesive bilayer matrices of narrow absorption window drug baclofen and the optimisation of their in vitro drug release and characterisation. Statistical design of experiments, a computer-aided optimisation technique, was used to identify critical factors, their interactions and ideal process conditions that accomplish the targeted response(s). A central composite design was employed to systematically optimise the drug delivery containing a polymer, filler and compression force. The values of ratio of different grades of hydroxypropyl methylcellulose, microcrystalline cellulose and compression force were varied to be fitted in design. Drug release at 1 h (Q1), 4 h (Q4), 8 h (Q8), 12 h (Q12), and hardness were taken as responses. Tablets were prepared by direct compression methods. The compressed tablets were evaluated for their hardness, weight variation, friability, content uniformity and diameter. Counter plots were drawn and optimum formulation was selected by desirability function. The formulations were checked for their ex vivo mucoadhesion. The experimental value of Q1, Q4, Q8, Q12 and hardness for check-point batch was found to be 31.64, 45.82, 73.27, 98.95% and 4.4 kg/cm(2), respectively. The release profile indicates Highuchi kinetics (Fickian transport) mechanism. The results of the statistical analysis of the data demonstrated significant interactions amongst the formulation variables, and the desirability function was demonstrated to be a powerful tool to predict the optimal formulation for the bilayer tablet.

Effect of iontophoresis and permeation enhancers on the permeation of an acyclovir gel.

The purpose of the present study was to explore the combined effect of chemical enhancers and iontophoresis on the in vitro permeation of acyclovir gel across porcine skin. Acyclovir gel was formulated using carbopol 940 and hydroxypropyl methylcellulose K4M (HPMC K4M). Effect of drug concentration on the delivery of acyclovir was examined. Increasing drug concentration of acyclovir enhanced its flux across the skin. Incorporation of permeation enhancers (menthol, n-methyl-2-pyrrolidone and polyethylene glycol 400) into the gel resulted in enhanced acyclovir permeation when combined with iontophoresis. Menthol showed the highest drug permeation and when combined with iontophoresis it significantly increased the acyclovir skin permeation.