Impact of gelation period on modified locust bean-alginate interpenetrating beads for oral glipizide delivery.

In this work, the effect of hydrogelation period in the design of glipizide-loaded biopolymer-based interpenetrating network (IPN) beads was investigated. Carboxymethyl locust bean gum and sodium alginate IPN beads were prepared by ionic crosslinking method using aqueous aluminium chloride salt solution as gelation medium. The longer exposure of the IPN beads in the gelation medium caused a considerable loss of the drug (∼ 8%), and also affected their surface morphology and drug release performance. Spherical shape of the IPN beads was observed under scanning electron microscope (SEM). The diameter of IPN beads increased with increasing gelation time. The IPNs cured for 0.5h exhibited slower drug release kinetics in HCl (pH 1.2) and phosphate buffer (pH 7.4) solution than those incubated for 1-2h. The drug release occurred at a faster rate in phosphate buffer solution and continued for a minimum period of 8h. The IPNs cured for the lowest period obeyed polymer chain-relaxation phenomenon as dominating mechanism for drug release. However, all the IPNs followed anomalous mechanism of drug transport. The drug release corroborated well with pH-dependent swelling behaviors of the IPNs. Thus, IPN beads cured for 0.5h were found most suitable for controlled delivery of BCS class II anti-diabetic drug glipizide.

Novel etherified locust bean gum-alginate hydrogels for controlled release of glipizide.

On many occasions, homopolysaccharide hydrogel networks alone are not suitable for controlled drug delivery. In this study, interpenetrating networks (IPNs) of sodium alginate (ALG) and etherified locust bean gum (ELBG) were developed through ionotropic gelation with Al(3+) ions, tested for glipizide release, and were compared with homopolymer hydrogel networks. The degree of reticulation in IPNs was explained by the neutralization equivalent, tensile strength measurement, and drying kinetics of drug-free hydrogels. IPNs afforded a maximum of 94.40 ± 0.35% drug entrapment efficiency and exhibited slower drug release profiles up to 8 h. Al(3+)-ALG network almost completed the release of embedded drug in 3.5 h; however, the homopolymer Al(3+)-ELBG network discharged their content at a slow, uniform rate up to 8 h like the IPNs. All the networks appeared spherical under scanning electron microscope. In all cases, a faster drug release rate was assumed in phosphate buffer (pH 7.4) than in KCl/HCl buffer (pH 1.2) solution. The pH-responsive swelling of the beads was responsible for the variable drug release rate in different media. NonFickian diffusion mechanism was operative for the transport of drug from the IPNs. Moreover, IPNs gained appreciation for their better mechanical strength (63.79 ± 1.59 MPa) than Al(3+)-ELBG network. Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry, and X-ray diffraction analyses indicated a compatible environment for drug encapsualtion and release from the IPNs. The drug release curves of Al(3+)-ELBG and IPNs were found similar to a reference product. Hence, Al(3+)-ELBG and IPNs could be useful in controlling diabetes over longer periods.

Tailoring of locust bean gum and development of hydrogel beads for controlled oral delivery of glipizide.

In this study, carboxymethyl derivative of locust bean gum was prepared, characterized, and its gelling ability with different concentrations (1-5% w/v) of aluminum chloride (AlCl(3)) was utilized for the development of glipizide-loaded beads in a completely aqueous environment. The beads were spherical when observed under a scanning electron microscope. Increase in gelling ion concentration decreased the drug entrapment efficiency from 97.68% to 95.14%. The beads swelled more slowly in pH 1.2 KCl-HCl buffer and exhibited a slower drug release pattern than that observed in pH 7.4 phosphate buffer. Irrespective of the dissolution media, the drug release became slower at higher AlCl(3) concentration. The drug release in alkaline medium was found to be controlled by a combination of diffusion as well as polymer relaxation phenomena. Comparing the release profiles, it was observed that the beads treated with 5% AlCl(3) provided slower drug release up to 10 h in alkaline medium without any sign of disintegration and, thus, this formulation was selected for further studies. Fourier transform infrared (FTIR) spectroscopy indicated the stable nature of the drug in the beads. Differential scanning calorimetry and X-ray diffraction analysis showed that most of the drug remained in amorphous state in the beads. Stability study indicated no statistical significant difference in drug entrapment efficiency of the beads. In vivo activity of the beads was tested and a prolonged hypoglycemic effect was achieved. Hence, carboxymethyl locust bean beads could be a potential carrier for controlled oral delivery of glipizide.

Orodispersible tablets: A new trend in drug delivery.

The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug-delivery system as they have improved patient compliance and have some additional advantages compared to other oral formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to super disintegrants in the formulation. Thus this type of drug delivery helps a proper peroral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method of preparation is the compression method. Other special methods are molding, melt granulation, phase-transition process, sublimation, freeze-drying, spray-drying, and effervescent method. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test, and dissolution test.

Investigation on processing variables for the preparation of fluconazole-loaded ethyl cellulose microspheres by modified multiple emulsion technique.

Fluconazole-loaded ethyl cellulose microspheres were prepared by alginate facilitated (water-in-oil)-in-water emulsion technology and the effects of various processing variables on the properties of microspheres were investigated. Scanning electron microscopy revealed spherical nature and smooth surface morphology of the microspheres except those prepared at higher concentration of emulsifiers and higher stirring speeds. The size of microspheres varied between 228 and 592 mum, and as high as 80% drug entrapment efficiency was obtained depending upon the processing variables. When compared up to 2 h, the drug release in pH 1.2 HCl solution was slower than in pH 7.4 phosphate buffer saline solution. However, this trend was reversed at high shear conditions. The microspheres provided extended drug release in alkaline dissolution medium and the drug release was found to be controlled by Fickian-diffusion mechanism. However, the mechanism shifted to anomalous diffusion at high shear rates and emulsifier concentrations. The aging of microspheres did not influence the drug release kinetics. However, the physical interaction between drug and excipients affected the drug dissolution behaviors. X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC) analysis revealed amorphous nature of drug in the microspheres. Fourier transform infrared (FTIR) spectroscopy indicated stable character of fluconazole in the microspheres. The stability testing data also supported the stable nature of fluconazole in the microspheres. The fluconazole extracted from 80% drug-loaded formulation showed good in vitro antifungal activity against Candida albicans. Thus, proper control of the processing variables involved in this modified multiple emulsion technology could allow effective incorporation of slightly water soluble drugs into ethyl cellulose microspheres without affecting drug stability.

Adipic acid dihydrazide treated partially oxidized alginate beads for sustained oral delivery of flurbiprofen.

In this study, periodate oxidation of sodium alginate was controlled such that the oxidized alginate could form isolatable beads with Ca(+2) ions. The beads of oxidized alginate having a degree of oxidation 1 mol%, entrapped 89% flurbiprofen and released almost all of its content within 1.5 h in pH 7.2 phosphate buffer solution. The beads were covalently crosslinked with adipic dihydrazide (ADH) in addition to ionic crosslinks and were characterized. Scanning electron microscopy revealed that the beads were spherical having smooth surfaces. The drug entrapment efficiency decreased (90-86%) with increasing concentration of ADH (2-6% w/v) in the gelation medium. However, the beads prolonged the drug release in alkaline dissolution medium up to 8 h depending upon the concentration of ADH. The beads prepared with 2% ADH swelled more rapidly and led to faster drug release in either pH 1.2 HCl solution or pH 7.2 phosphate buffer solution. The swelling tendencies were reduced and the drug release became slower with higher concentrations in either fluid. The drug diffusion from the beads followed super case II transport mechanism. FTIR spectroscopy indicated stable nature of flurbiprofen in the beads and therefore had potential as sustained oral delivery system for the drug.