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3.1 PREFORMULION STUDIES:
3.1.1. IDENTIICAION OF DRUG:
Identification of drug was carried out by following methods.
Color: Yellowish white tobright yellow, crystals or crysalline powder.
Solubility: Slightly soluble in water, soluble in glacial acetic acid, slightly soluble or soluble in dichloromethane, slightly soluble in methanol.
Physical state: Solid
Melting point: 250-257 0C, which was determied by capillary method.
3.1.2. SOLUBILITY STUDIES:
TABLE NO. 3.1: Solubility data of drug in different solvents:
Solvent Concentration (mg/ml) Solubility
Methanol 5 Soluble
Distilled Water 5 Slightly soluble
Ether 5 Insoluble
0.1 N NaOH 5 Insoluble
Glacial acetic acid 5 Soluble
Dichloromethane 5 Slightly soluble
0.1N HCl 5 Soluble
3.1.3. LOSS ON DRYING:
TABLE NO. 3.2: Percentage loss on drying of Ofloxacin
S. No. Weight of drug before drying (gm) Weight of drug after drying (gm) Loss on drying
(%w/w) Average LOD (%w/w) Limits
1 1 0.9974 0.26 0.27 0.1-0.4
2 1 0.9972 0.28
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3.1.4. DRUG-EXCIPIENT INTERACTION BY FTIR:
Fourier transform infrared spectroscopy:
FTIR is the most important analytical technique, to determine the structure of the compound, by predicting the presence of certain functional groups in the compound which can be observed at definite frequency and to study the drug polymer interaction.
The spectra were recorded for Ofloxacin, Sodium alginate, Guar gum, HPMC.
Fig. 1 FTIR spectra of pure drug Ofloxacin:
TABLE NO. 3.3: Peaks of Ofloxacin
Functional groups Peak range (cm-1 )
C-H bending 952.84
C-F 1051.20
-OH group 1400.32
C=C stretching 1473.62
C=C bending 1519.91-1548.81
C=O group of acid 1718.58
C-H stretching 3041.74
FTIR spectra of polymer:
Sodium alginate
Fig. 2 FTIR spectra of sodium alginate
TABLE NO. 3.4: Peaks of Sodium alginate
Functional groups Peak range (cm-1 )
C-O-C stretching 1026.13
Symmetrical acid stretching 1404.18
Asymmetrical acid stretching 1622.13
O-H stretching 3396.64
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FTIR spectra of guar gum:
Fig. 3 FTIR spectra of Guar gum
TABLE NO. 3.5: Peaks of Guar gum:
Functional groups Peak range (cm-1 )
C-H deformation 873.75
CH2twisting 1020.34-1087.85
CH2and C-OH symmetric deformation 1415.71
Ring stretching 1641.42
C-H stretching 2926.01
-OH group 3363.86
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FTIR spectra of HPMC:
Fig. 4 FTIR spectra of HPMC
TABLE NO. 3.6: Peaks of HPMC:
Functional groups Peak range (cm-1 )
Pyranose asymmetrical 945.12
C-O-C vibration 1064.71-1118.71
C-O-C symmetrical 1377.17
O-CH3asymmetricbending 1460.11
C-O stretching 1645.28
-OH group 3454.51
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FTIR spectra of combination of drug and polymer:
Fig. 5 FTIR spectra of combination of drug and polymer
TABLE NO. 3.7: Peaks of combination of drug and polymer
Functional groups Peak range (cm-1 )
OH bonding 1020.34
C-O-C vibration 1118.71
C-O-C symmetrical 1280.73
C-H stretching 1429.25
Symmetrical stretching of O-C-O of acid 1627.92
Hydrogen bonded OH 3431.36-3523.95
Free OH 3682.11
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3.1.5 PREPARATION OF STANDARD CURVE IN 0.1NHCl & METHANOL:
Fig. 6. Standard curve of Ofloxacin in 0.1N HCl
Fig. 7. Standard curve of Ofloxacin in Methanol:
3.2. PHYSICOCHEMICAL CHARACTERIZATION:
3.2.1. PARTICLE SIZE DISTRIBUTION:
Particle size distribution and average particle size was determined microscopically.
TABLE NO. 3.8: Particle size distribution
S. No. Formulation code Mean Particle size (µm)
1 F1 57.3 ± 7.6
2 F2 63.5 ± 7.98
3 F3 64.1 ± 7.99
4 F4 61.2 ± 7.52
5 F5 55.3 ± 7.39
6 F6 58.6 ± 7.52
7 F7 57.9 ± 7.46
8 F8 58.4 ± 7.51
9 F9 61.7 ± 7.55
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3.2.2. MORPHOLOGY:
Morphology of alginate beads were observed by scanning electron microscopy (SEM). The shape and surface of particles are also important in terms of drug release.
Fig. No. 8. Scanning electron microscopy (SEM) of Formulation 1.
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Fig. No. 9. Scanning electron microscopy (SEM) of Formulation 2.
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3.2.3. YIELD OR MICROPARTICLE RECOVERY:
The prepared alginate beads were dried under the vaccum. After proper drying the weight of the beads were measured and the yield was calculated from the following equation,
% Yield = Weight of recovered particles x 100
Weigh of drug and polymer used
TABLE NO. 3.9: Percentage yield of different formulations:
S. No. Formulation Percentage yield
1 F1 31.69
2 F2 34.62
3 F3 30.53
4 F4 47.16
5 F5 46
6 F6 43.19
7 F7 32.05
8 F8 29
9 F9 29.41
3.2.4. DRUG ENTRAPMENT EFFICIENCY:
An accurately weighed quantity of dried beads were crushed in mortar and added to 100 ml of suitable solvent. After complete dissolution of the beads, the solution was filtered and analyzed spectrophotometrically. The percentage drug loading and entrapment efficiency was calculated.
Drug entrapment efficiency = Weight of drug in alginate beads x 100 Weigh of drug used
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TABLE NO. 3.10: Drug entrapment efficiency of different formulations:
S. No. Formulations Drug entrapment efficiency
1 F1 40.29
2 F2 44.16
3 F3 58.37
4 F4 47.42
5 F5 60.12
6 F6 56.34
7 F7 71.35
8 F8 69.31
9 F9 62.28
3.3 FLOATING PROPERTIES:
TABLE NO. 3.11: Floating properties of different formulations:
S. No. Formulations code Floating lag time Floating time
1 F1 < 30 sec > 24 hrs
2 F2 < 30 sec > 24 hrs
3 F3 < 30 sec > 24 hrs
4 F4 < 30 sec > 24 hrs
5 F5 < 30 sec > 24 hrs
6 F6 < 30 sec > 24 hrs
7 F7 < 30 sec > 24 hrs
8 F8 < 30 sec > 24 hrs
9 F9 < 30 sec > 24 hrs
Floating ability of the prepared alginate beads was evaluated in 0.1N HCl and it was found that all the formulation floated immediately or with a very short lag time of about less than 30 second only. Similarly floating time of all the batches was about more than 24 hours. The results prove that all the batches have good floating property.
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3.4 IN-VITRO DRUG RELEASE STUDY:
Release of drug was performed on the beads by using dissolution apparatus USP type I. A weighed amount of individual beads formulation were added to the dissolution vessel, which contains sufficient amount of dissolution media at 370C. At set times, samples were collected, filtered and the amount of drug released was assayed by proper analytical technique.
TABLE NO. 3.12: Cumulative percentage of drug release:
Time
(hrs.) F1 F2 F3 F4 F5 F6 F7 F8 F9
1 6.14 5.48 7.24 6.74 8.26 7.36 8.42 9.53 6.71
2 12.48 12.14 12.56 11.43 14.39 12.69 14.23 16.41 13.48
3 18.23 17.63 18.63 16.65 21.23 18.26 19.34 24.16 21.14
4 23.42 21.84 24.78 22.46 26.12 23.52 26.54 31.18 29.56
5 30.52 25.46 29.35 27.93 31.48 28.42 31.42 37.45 36.48
6 32.16 29.38 34.85 33.14 36.78 34.26 36.74 42.65 44.19
7 35.68 33.42 40.09 38.56 42.86 39.78 42.34 49.23 51.75
8 40.27 38.65 43.28 42.64 46.72 44.65 47.13 54.26 57.64
9 42.61 43.12 46.42 47.26 51.48 50.12 53.71 61.28 64.28
10 45.32 47.52 51.49 52.83 55.61 57.48 58.45 66.35 70.42
22 54.12 56.24 61.48 63.08 63.75 66.71 67.14 74.26 81.36
23 63.65 67.49 69.26 71.65 71.32 72.64 75.78 82.56 86.12
24 72.28 74.58 76.12 77.42 72.68 78.84 81.36 86.34 92.43
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3.5 RELEASE KINETICS EVALUATION:
By analyzing release kinetics mathematical models it is found that foe all formulations, the correlation coefficient, is highest in case of Higuchi kinetics. Therefore it can be said that the release follows Higuchi kinetics moreover the R2 value of zero order kinetics is higher than that of first order kinetics and it is near to that of Higuchi kinetics. Therefore release is following mixed kinetics or Higuchi kinetics.
Fig. no. 10: Zero order release kinetic model
Fig. no. 11: First order release kinetic model
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Fig. no. 12: Higuchi release kinetic model
TABLE NO. 3.13: R2 values or correlation coefficient values of different formulations:
S. No. Formulation code Zero order release kinetics First order release kinetics Higuchi release kinetics
1 F1 0.8811 0.6425 0.9537
2 F2 0.9088 0.6774 0.9640
3 F3 0.8872 0.6637 0.9626
4 F4 0.8969 0.6793 0.9650
5 F5 0.8505 0.6406 0.9457
6 F6 0.8851 0.6790 0.9586
7 F7 0.8755 0.6726 0.9542
8 F8 0.8440 0.6361 0.9404
9 F9 0.8398 0.6012 0.9378
3.6 STABILITY STUDIES:
Prepared alginate beads were divided at different parts and were placed at different vials at different temperature and humidity for 90 days. The sample from different container was periodically evaluated for physical and chemical stability.
TABLE NO. 3.14: Stability data at 40¬¬oC and 75 % relative humidity
Duration Agglomeration Drug content (%) Drug release at 8 hours (%)
F2 F5 F8 F2 F5 F8 F2 F5 F8
30 days No change No change Agglom
eration 51.85 55.23 52.84 71.67 74.07 73.19
60 days Agglom
eration No change Damage 50.64 52.07 _ 69.82 73.52 _
90 days Damage No change Damage _ 51.16 _ _ 69.27 _
From the above table of stability data is clear that, microparticles are not proper stable at this stability condition. There is no further change in the formulation F5 for agglomeration, but F2 and F8 ¬ agglomerate after a definite period of time and finally damage, which shows that they are unstable. Drug content and drug release also decreases, after a definite period of time for all selected formulations.
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CONCLUSION
In the present research work, floating beads of Ofloxacin were formulated to achieve sustain release of drug in the absorption window if gastrointestinal tract The sodium alginate beads were prepared with Guar gum and Hydroxy Propyl Methyl Cellulose, showed better loading and floating characteristics. In this work, spherically well shaped microbeads were produced using the polymers guar gum and Hydroxy propyl methyl cellulose. Preformulation studies of drug were attempted regarding melting point, solubiliy analysis, UV spectrophotometric analysis and FTIR analysis to identify and assesment of purity of drug. The recovered microbeads were evaluated for particle size analysis, drug entrapment efficiency, percentage yield, FTIR study, morphology, in-vitro drug release study and release kinetic evaluation.
In-vitro drug release study from every formulation was conducted for 24 hours. The release data were further analyzed to curve fitting into mathematical model, which shows that drug release kinetics follow Higuchi kinetics mathematical model.
Preformulation study revealed the purity of drug. The solubiliy of drug in methanol was found to be satisfactory to study the drug release into this media. UV-spectrophotometric analysis of drug into both 0.1N HCl and methanol revealed the suitability of the standard curve for further calculations. Average particle size of selective formulation was at the range of 55.3 µm 64.1 µm which shows that particles are smallee in size, which provide uniform distribution of drug release in thebody. From the above table of floating properties, it is clear that the all formulations floated immediately and with a very short lag time about less than 30 seconds. Similarly floating time of all the formulations is about more than 24 hours. This result proves that all the batches have good floating property.
The morphology of microbeads was determined by scanning electron microscopy, which shows that particles are nearly spherical in shape and with slightly rough surface, which may attribute to the uniform release of drug. Microparticles recovery was found to be 29 % to 47.16 % in all formulations, drug entrapment efficiency was at the range of 40.29 % to 71.35 % and drug release at 24 hours was found to be at the range of 72.28 % to 92.43 % in all formulations. These values ensure the high yield and entrapment efficiency of the microbeads. Moreover the release kinetics evaluation revealed that the formulation was following Higuchi Kinetic mathematical model.
From the result obtained, in drug release study we conducted that F9 formulation have higher percentage of drug release (92.43 %), and same formulation also have short lag time abut less than 30 seconds only and floating time is about more than 24 hours, which shows that it has good floating property or buoyancy. Therefore, we conclude that F9 formulation is the best formulation as compared to other formulations.
The data obtained from the current work suggest the possibility of using microparticles as a sustained release gastroretentive drug delivery system which has lower density than gastric fluids and so these remain floating in the stomach without affecting the gastric emptying rate for a prolonged period of time. For the purpose of future use, these floating sustain release gastroretentive microbeads are suitable drug delivery system for the treatment of microbial infection.
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