FTIR Spectroscopy Analysis:
The FTIR spectra of Miglitol pure drug and optimized formulation (F6) were carried out. The Miglitol pure dug prominent peak at 3392 cm-1 and 1235- 1168 cm-1 indicates the O-H stretching and bending vibration. C-H stretching vibration prominent peak shown at 2851- 2820 cm-1. C-C stretching vibration peak was showing at 1454 and 1471cm-1. Prominent peak at 1260cm-1 and 1140-1020 cm-1 indicates C-N stretching and C-O stretching bands were observed  Figure 1 (A). The FTIR spectra of optimized formulation floating microsphere were showing imbricate of the Miglitol pure drug characteristic peak in Figure 1 (B). So it was indicating no drug polymer interaction, and Miglitol pure drug was stable in it’s nature after encapsulation process.
Characterization floating of Microsphere:
Drug Entrapment Efficiency:
The drug entrapment efficiency of the all formulations of floating microsphere was found to be in the range of 86.57% - 70.82 %. Drug entrapment efficiency was increasing with increase in Ethyl cellulose: Eudragit E100 polymer ratio. Because as the polymer concentration is increased, the polymer coats more drug particles, increasing the drug entrapment efficiency. The DEE percentage is showed in Table 3.
The percentage of buoyancy of the floating microspheres in all formulations was found to be between 94.25% and 73.23%. The % buoyancy was increased due to increase in the polymer mixture concentration. The floating microsphere was floated in the simulated gastric juice for more than 12hrs. This means that the microsphere will be retained on the gastric juice for a longer period of time in order to enhance the gastric residence time of the dosage form. Table 3 displays the percentage of buoyancy.
Determination of Particle size:
The particle size determination has been carried out for all formulations of floating microspheres, and was found to be in the range from 670.42 µm – 410.45µm. It was observed that as the Ethyl cellulose: Eudragit E100 polymer ratio increased the particle size also increased. Because, the consistency of solution will increase with polymer ratios, resulting in increased particle size. Floating microsphere with mean particle size range from 500µm-1000µm, have been reported to possess higher floating ability . Table 3 showed the measured particle size effects.
Scanning Electron Microscopy:
The optimized floating microsphere (F6) surface morphology was explored by SEM. It has been examined at different magnification of 60X and 100X. The images of microspheres were almost smooth and spherical shape and the small porous cavities were found on the surface of microspheres, which will aid in improving the floating property of microspheres. The F9 formulation of floating microspheres prepared higher ethyl cellulose and eudragit E100 ratios has shown rough surface in SEM images. This is attributed to increased polymer concentration increases particle size with rough surface. It’s showed in Figure 2 (A) & (B).
The percentage yield of all floating microsphere formulations was calculated. The calculated percentage yield ranged between 98.76% - 91.656%. It indicates that the increased polymer concentration in microspheres leads to increased percentage yield. The calculated percentage yield is showed in Table 3.
All nine formulations were evaluated for floating lag time, and the floating microsphere lag time was zero seconds for all formulations. Because, all the floating microsphere formulations possess floating property, when they are added to simulated gastric fluid, microsphere will not go into the solvent and it will just float on the simulated gastric fluid. As a result, the floating lag time would be zero second.
In vitro drug release study:
In vitro drug release study of floating microsphere was conducted for 12hrs using 0.1N HCl pH1.2 as a release medium by using USP type-2 dissolution apparatus. After 12 hours, the cumulative drug release of all 9 formulations showed that Formulation F9 had the highest cumulative drug release and Formulation F6 had the lowest cumulative drug release. The increased polymer concentration results in more amount of polymer coating around the drug that ultimately decreases the cumulative percent drug release. The cumulative percentage drug release was performed triplicates and the data was plotted in graph it has shown in Figure 3.
Release kinetic study:
The data was obtained from in vitro drug release study and it has plotted in different kinetic models. The all formulations were showing the zero order kinetic model with maximum R2 value. Zero order kinetic model is the best fit model for sustained release dosage forms. As per the n-value of peppas model which was between 0.5 to 1, so mechanism was non- fickian transport . The kinetic model fitting release profile of all formulation results are given in Table 4.
According to ICH guidelines, all formulations were tested for stability for 30, 60 and 90 days. There was slight variation in shown in buoyancy and in-vitro drug of Miglitol floating microspheres on 90th day at (40ºC ± 2ºC and 75% ± 5%). F6 formulations buoyancy was found to be 88.21% and in-vitro drug release was found to be 62.87%. F10 formulations buoyancy was found to be 87.22% and in vitro drug release was found to be 63.51%. There were no colour variations in the physical appearance of any of the Miglitol floating microsphere formulations, and there was no overlap on other particles.
Optimization of floating microsphere:
Based on pilot study report, selected polymer concentration and stirring speed Miglitol floating microsphere was prepared by using JMP® software 32 factorial designs (3 level 2 factor). Independent variables was polymer concentration A (Ethyl cellulose), B (Eudragit E100) 3 levels (-1, 0, +1) 500, 600, 700 and dependent variables was drug entrapment efficiency and percentage buoyancy. Miglitol floating microsphere was prepared by double emulsion method because of Miglitol is freely soluble in water to confirm with available literature and text books.
The optimization studies were performed in order to select the best polymer concentration of ethyl cellulose and eudragit E100 to obtain the maximum drug entrapment efficiency and buoyancy. As the polymer concentration (ethyl cellulose and eudragit e100) increase buoyancy and drug entrapment also increase simultaneously.
ANOVA was analysed with data, it was obtained that it follows quadratic model R2 value for % of buoyancy was 0.9866 and drug entrapment was 0.9920.
The Equation for the buoyancy and drug entrapment efficiency 1 and 2 respectively,
(Y1) = 85.38+ 6.77 A+ 4.67 B- 1.50 AB- 0.3427 A2 + 0.1183 B2……. (1)
(Y2) = 89.01+ 4.68 A+ 4.48 B- 1.58 AB+ 0.0567 A2+ 2.16 B2……….. (2)
Where, A and B represents the polymer concentration (-1, 0, +1) of Ethyl cellulose and Euduragit E100 respectively.
Statistical analysis of response Y1 buoyancy shows that the quadratic model F- value is 44.15 it’s indicate the model is significant. The value of p should be less than 0.05 obtained p value is 0.0052, this implies the model terms are significant. After examining the quantity of co efficient and the mathematical sign it exhibits, the polynomial equation can be used to reach at a conclusion.
Statistical analysis of response Y2 drug entrapment efficiency shows that the quadratic model F- value is 74.12 its indicate the model is significant. The value of p should be less than 0.05 obtained p value is 0.0024, this implies the model terms are significant. After examining the quantity of co efficient and the mathematical sign it exhibits, the polynomial equation can be used to reach at a conclusion.
Design space is a multivariate mixture and interaction of independent factors and process factors that has been proved to enable quality assurance. To build design space and optimise all of the replies, a numerical optimization approach (desirability function) and a graphical optimization approach (overlay plot) were utilised.
Constraints on the dependent response and independent factors were used to obtain at the optimum formulation. The response, buoyancy, and drug entrapment efficiency restrictions were fixed at range between 90-95 % and 95-98 %, respectively. As a result, because it falls in the yellow area of the overlay plot, with desirability equal to 1, Formulation F10 was regarded an optimum formulation. The optimised formulation would have a level of X1 (ethyl cellulose) = 690.85 and X2 (eudragit E100) = 674.10, with predicted buoyancy and drug entrapment effectiveness of 93.82 % and 98.06 % respectively. The calculated results value of buoyancy (92.41%) and drug entrapment efficiency (97.45%) were quite similar to the model's expected values. F10 formulation was prepared to check the predicted and actual factors and compared with optimized formulation F6. The data has been optimised, as shown in the Table 5 and Figures 4, 5 and 6 below.