Preparation And Characterization Of Anti Diabetic Drug Glimepirid

Published Date: 02 Nov 2017

Abstract :

Films of chitosan and PEG with Glimepiride as model drug combined at different concentration .The films are obtained by solvent evaporation method. Prepared film were characterized both physical and chemical characterization. To observe the compatibility between different polymer with model drug.

Key word : Films,PEG,Glimepirid,Chitoson.

Introduction :

Chitosan, the DE acetylated derivative of chitin, is one of the most abundant naturally occurring polysaccharides. Recently, it has attracted much interest in the biomedical industry because of its excellent biodegradability, biocompatibility, antimicrobial activity and accelerated wound-healing properties Chitosan has good blend Film forming properties. When it is dissolved in dilute acetic acid solutions, the amino groups become protonated and associated with acetate counter-ions, making the charged polymer soluble. Therefore, net negatively charged compounds such as DNA, glycosaminoglycan’s, and most proteins can be incorporated into chitosan without the use of harsh and denaturing organic solvents, such as methylene chloride, which are needed for Film preparation of many biodegradable polymers.

Materials and methods:

Materials : Chitosan,PEG,Films

Preparation of drug loaded Films :

Chitosan/PEG drug loaded Films were produced by a casting/solvent evaporation technique. Solutions of chitosan and PEG, 2wt%, were prepared with 2wt% acetic acid solution and distilled water, respectively; and the PEG was dissolved in a higher temperature. These solutions were mixed in different proportions to obtain final PEG solution concentrations of 2.0, 3.5, 5.5 and 8.0wt% of total. Glimepiride hydrochloride (0.2 g) was dissolved, under stirring, in each one of these four resulting solutions (50ml) to make them completely homogeneous. After that, they were sonicated in a sonication bath, left to stand until trapped air bubbles were removed, and poured on a Teflon plate of 20£15 cm2. These Films were dried in an oven at 37 °C for 48 h, and finally dried under vacuum at room temperature until constant weight. These dried Films, with an average thickness of 55 _m determined by WHS-10A Portable Thickness Instrument, and were cut into 3 £3 cm 2 sections for tests. The several chitosan/PEG drug loaded Films, prepared with Glimepiride, were designated as CP-1, CP-2, CP-3 and CP-4 (PEG contents were 2.0, 3.5, 5.5 and 8.0wt%, respectively). The blank matrix Film, without the drug, was marked with CP (PEG was 3.5wt %).

FT-IR analysis

The FT-IR spectra of pure chitosan, PEG Glimepiride, CP and CP-4 Films were recorded within KBr pellets on a Nicolet FTIR spectrometer.

X-ray diffraction studies

The X-ray diffraction patterns of pure chitosan, PEG, Glimepiride, CP and CP-4 Films were determined on a diffractometer , using Nickel-filtered CuK_ radiation at 40 kV and 50mA in the 2_ range of 5°–40°. From the results of CP and CP-4 Films, the effects of Glimepiride on the degree of crystallization of the blend Films were determined.

Release studies

The drug loaded Films were suspended in glass vessels containing 50ml of medium, as specified below, and incubated on a shaking bed at 37 °C, 130rpm. At appropriate time intervals aliquots of the solutions were withdrawn and the amount of Glimepiride released from the drug loaded Films were evaluated by UV spectrophotometry 277 nm. Then an equal volume of the same dissolution medium was added back to maintain a constant volume. The medium for the controlled release studies were four typical solutions: pH 1.0 (0.1M HCl solution, acts as simulated gastric fluid), pH 3.6 and pH 5.0 (10mM solution acetate buffer), and pH 7.4 (10mM NaH2PO4–Na2HPO4- buffered solution, acts as simulated intestinal fluid). The ionic strength of the above buffered solutions was carefully adjusted to a relatively level by adding an appropriate amount of NaCl. All the experiments were done in triplicate.

Results and discussion

FT-IR analysis

Release studies

Effect of the composition ratio of drug loaded Film

The influence of the different composition ratios of chitosan and PEG in the drug loaded Films CP-1, CP-2, CP-3 and CP-4 (2, 3.5, 5.5 and 8wt% of PEG, respectively) on the release into 10mM sodium phosphate buffer, pH 7.4 (ionic strength of 0.145M) was such that the release rate of Glimepiride increased with increase content of PEG. Because PEG is somewhat soluble in these aqueous solutions, it dissolves and leaves pores that accelerate the release of the drug from the matrix Film.

Effect of the drug loaded amount

Testing of Films CPC-1, CP-2 and CPC-2 with different loaded amounts (0.1, 0.2 and 0.3 g, respectively) showed that the more drug was loaded, the lower the cumulative drug release rate was; but according to the fact that more drugs were loaded, the cumulative release amount is increasing. So more persistent release can be achieved by increasing the drug-loaded amount.

Effect of pH

The drug release from loaded Film CP-2, in four different buffered solutions with pH values of 1.0, 3.6, 5.0 and 7.4, (ionic strength all adjusted to 0.145M, by adding an appropriate amount of NaCl) was very sensitive to the pH of the medium. The release was accelerated with decrease of pH, because the electrostatic interaction between anions and chitosan was greatly influenced by solution pH. The decrease of pH weakened salt bonds and therefore, facilitated Film swelling, thereby accelerating drug release. The pH also has a slight effect on the solubility of Glimepiride. A higher pH leads to a better solubility of Glimepiride, which results in higher drug release rate. But compared to the strong influence of pH on the Film matrix, pH effects on Glimepiride could be neglected.

Conclusions

Drug loaded Films based on chitosan and PEG, were produced by a casting/solvent evaporation method. With Glimepiride as a model drug, we studied the Films’ structures and characteristics, especially its potential capacity in drug delivery system. The chemical and morphological characterizations showed that there is a good compatibility between the matrix Film and the drug used due to both kinds of strong interactions namely hydrogen bonds and ionic interactions. The Films’ mechanical property is also good. The results of controlled release tests showed that the amount of Glimepiride released increased with an increase in the proportion of PEG and decreased as the amount of drug loaded in the Film increased; however, the cumulative release amount of the drug increased. The chitosan/PEG Films were also sensitive to pH and ionic strength. The thickness of the Film will slow the drug release process. The higher concentration of sodium alginate coating solution reduced the release of Glimepiride. Furthermore, the longer crosslinking time of these Films in the TPP solution, the lower drug release rate attained within 24 h. Thus, we can control the drug release rate through changing some influential factors of the drug loaded Film. The Film can lead to a successful application for localized drug delivery in vivo or in vitro environment.