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.

pH-sensitive hydrogels based on semi-interpenetrating network (semi-IPN) of chitosan and polyvinyl pyrrolidone for clarithromycin release.

The aim of this study was to develop a pH-sensitive chitosan/polyvinyl pyrrolidone (PVP) based controlled drug release system for clarithromycin. The hydrogels were synthesized by cross-linking chitosan and PVP blend with glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN). These semi-IPNs were studied for their content uniformity, swelling index (SI), mucoadhesion, wettability, in vitro release and their release kinetics. The hydrogels showed more than 97% content of clarithromycin. These hydrogels showed high swelling and mucoadhesion under acidic conditions. The swelling may be due to the protonation of a primary amino group on chitosan. In acidic condition, chitosan would be ionized, and adhesion could have occurred between the positively charged chitosan and the negatively charged mucus. In the alkaline condition, less swelling and mucoadhesion was noticed. In vitro release study revealed that formulation containing chitosan (2% w/v) and PVP (4% w/v) in the ratio of 21:4 showed complete drug release after 12 h. Release profile showed that all the formulations followed non-Fickian diffusion mechanism. The cross-linking and compatibility of clarithromycin in the formulation was studied by Fourier transform infrared (FTIR) spectroscopic analysis, differential scanning calorimetry (DSC) and powder X-ray diffraction (p-XRD) study, which confirmed proper formation of semi-IPN and stability of clarithromycin in the formulations. The surface morphology of semi-IPN was studied before and after dissolution in simulated gastric fluid (SGF, pH 1.2) which revealed pores formation in membrane after dissolution. The results of study suggest that semi-IPNs of chitosan/PVP are potent candidates for delivery of clarithromycin in acidic environment.

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.

Synthesis and characterization of pH-sensitive hydrogel composed of carboxymethyl chitosan for colon targeted delivery of ornidazole.

In the present study, carboxymethyl chitosan was prepared from chitosan, crosslinked with glutaraldehyde and evaluated in vitro as a potential carrier for colon targeted drug delivery of ornidazole. Ornidazole was incorporated at the time of crosslinking of carboxymethyl chitosan. The chitosan was evaluated for its degree of deacetylation (DD) and average molecular weight; which were found to be 84.6% and 3.5×10(4) Da, respectively. The degree of substitution on prepared carboxymethyl chitosan was found to be 0.68. All hydrogel formulations showed more than 85% and 74% yield and drug loading, respectively. The swelling behaviour of prepared hydrogels checked in different pH values, 1.2, 6.8 and 7.4, indicated pH responsive swelling characteristic with very less swelling at pH 1.2 and quick swelling at pH 6.8 followed by linear swelling at pH 7.4 with slight increase. In vitro release profile was carried out at the same conditions as in swelling and drug release was found to be dependant on swelling of hydrogels and showed biphasic release pattern with non-fickian diffusion kinetics at higher pH. The carboxymethylation of chitosan, entrapment of drug and its interaction in prepared hydrogels were checked by FTIR, (1)H NMR, DSC and p-XRD studies, which confirmed formation of carboxymethyl chitosan from chitosan and absence of any significant chemical change in ornidazole after being entrapped in crosslinked hydrogel formulations. The surface morphology of formulation S6 checked before and after dissolution, revealed open channel like pores formation after dissolution.

Synthesis and characterization of carboxymethyl chitosan hydrogel: application as pH-sensitive delivery for nateglinide.

In current research, chitosan was reacted with mono-chloroacetic acid under alkaline condition to prepare carboxymethyl chitosan (CMCTs). The degree of substitution (Ds) on prepared CMCTs was found to be 0.68. CMCTs was used as a potential carrier for pH specific delivery of nateglinide after crosslinked using glutaraldehyde in presence of nateglinide. The average molecular weight and degree of deacetylation (DD) of chitosan were found to be 3.5x104 Da and 84.6% respectively. High yield (82%) and loading of drug (75%) were found in the developed hydrogel formulations. pH responsive swelling behavior of prepared hydrogels was checked using different pH values (1.2, 6.8 and 7.4). The study indicated very less swelling at pH 1.2 (for first 2 h) and quick swelling at pH 6.8 (for next 3 h) followed by linear swelling at pH 7.4 (for next 7 h) with slight increase. In vitro release profile of hydrogels showed biphasic release pattern dependent on swelling behavior. The release pattern was found to be non-fickian diffusion kinetics at higher pH. FTIR, 1H-NMR, DSC and p-XRD studies were carried out to confirm the formation of CMCTs, drug entrapment and its possible interaction in formulations. These studies revealed that no chemical change was found in nateglinide during preparation of hydrogel formulations. Scanning Electron Microscopy (SEM) was used to study the surface morphology of prepared hydrogels before and after dissolution which revealed pores formation after dissolution.

Hydrogels based on interpenetrating network of chitosan and polyvinyl pyrrolidone for pH-sensitive delivery of repaglinide.

The aim of this study was to develop a pH-sensitive chitosan/polyvinyl pyrrolidone (PVP) based controlled drug release system for repaglinide. The hydrogels were synthesised by crosslinking chitosan and PVP blend with glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN). These semi-IPNs were studied for their content uniformity, swelling index (SI), mucoadhesion, wettability, in vitro release and their release kinetics. The hydrogels showed more than 95% loading of repaglinide. These hydrogels showed high swelling and mucoadhesion under acidic conditions. The swelling was found due to the protonation of a primary amino group on chitosan. In acidic condition chitosan was ionized, and adhesion occurred between the positively charged chitosan and the negatively charged mucus. In the physiological condition less swelling was noticed. In vitro release study revealed that formulation containing chitosan (2% w/v) and PVP (4% w/v) in the ratio of 14:6 w/w showed complete drug release after 12h. Release profile showed that all the formulations followed non-fickian diffusion mechanism (diffusion coupled with swelling). Fourier transform infrared (FTIR) spectroscopic analysis revealed proper crosslinking of polymer and formation of semi-IPN as well as presence of drug in the formulation. Differential scanning calorimetry (DSC) and powder x-ray diffraction (p-XRD) study revealed the presence of repaglinide in crystalline form in the formulations. The surface morphology of semi-IPN was studied before and after dissolution in simulated gastric fluid (SGF, pH 1.2) which indicated generation of open channel-like structure in hydrogel after dissolution. The results of study suggest that semi-IPNs of chitosan/PVP are potent candidates for delivery of repaglinide in acidic environment.

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.

Cyclosporine a-nanosuspension: formulation, characterization and in vivo comparison with a marketed formulation.

Cyclosporine A-nanosuspensions were prepared using zirconium oxide beads as a milling media, Poloxamer 407 as a stabilizer and distilled water as an aqueous medium using the Pearl Milling technique. The optimized formulation was characterized in terms of particle size distribution, surface morphology, drug-surfactant interaction, drug content, saturation solubility, osmolarity, and stability. The nanoparticles consisting of Poloxamer-bound cyclosporin A with a mean diameter of 213 nm revealed a spherical shape and 5.69 fold increased saturation solubility as compared to the parent drug. The formulation was found to be iso-osmolar with blood and stable up to 3 months at 2â8ÂC. In-vivo studies were carried out in albino rats and the pharmacokinetic parameters were compared with a marketed formulation, which indicated better results of the prepared formulation than the marketed one.