Department of Pharmaceutics, YSPM's, Yashoda Technical Campus, Satara, Maharashtra, India.
The aim of the present study is desin and development of immediate release tablet using kollidon 90f as carrier. For immediate release of drugs from tablets, the superdisintegrants sodium strach glycolate (SSG), crospovidone (CP), and croscarmellose sodium (CCS) were employed. Every pre-compression and post-compression parameter was assessed for the manufactured tablets. By using FTIR, the drug-excipient interaction was examined. Every formulation demonstrated adherence to pharmacopoeial guidelines. According to the study, glipizide formulations generated by direct compression F6 demonstrate the maximum dissolution utilizing crospovidone and faster drug release, 92.74% over a 60-minute period.
In addition to providing patients with a convenient dose form or regimen, a rapid release dosage form helps a firm to maintain market exclusivity. Fast dispersing drug delivery systems and immediate release tablets may be able to address these issues. Immediate release tablets are made to dissolve and release their medication without the need for additional rate-controlling elements like coatings or other methods [1,2]. In recent times, instant release tablets have gained popularity and acceptability as a medication delivery strategy. This is mostly due to their convenience of administration, early onset of action, affordability, and ability to improve patient compliance. They are a tool for creating opportunities, extending product life cycle. [3,4] Glipizide is a sulfonylurea class oral antidiabetic drug that is frequently administered to treat type 2 diabetes mellitus. It works by inducing the pancreas to release more insulin, which lowers blood glucose levels. Insulin is a hormone that aids in the uptake of glucose into cells so that it can be used as fuel. This helps control blood sugar levels. It is significant to remember that people with type 2 diabetes who are unable to control their blood sugar levels by lifestyle changes are usually prescribed Glipizide.
Every material utilized in the experiment was either LR grade or the finest pharma grade provided by the manufacturer.
Using various ratios of superdisintegrants, glipizide tablets were produced for five batches, F1 to F5. ensuring that the tablet's overall weight (100 mg) remains consistent throughout all formulations. Using the recipe in Table 3, imipramine hydrochloride tablets were made using the direct compression technique. The superdisintegrants, sodium starch glycolate, crospovidone, and croscarmellose sodium, have been used in varying ratios.
The ingredients underwent a drying process at temperatures ranging from 40 to 450 degrees Celsius after being filtered through sieve #40. Weighed amount drug and excipients except magnesium stearate and talc were mixed for Approximately 20 minutes. geometric mixing was used to ensure that the drugs and excipients were properly mixed . The first combination was thoroughly combined and blended with talc and magnesium stearate after they were run through filter #80. A 2 mm diameter round concave punch with a force of 58.5 kN was used to compress the mixture of medication and excipients on a rotary punching machine.
Table no 1. Formulation of glipizide Immediate release table
|
Ingredients (mg/tablet) |
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
|
Solid dispersion glipizide |
10 |
10 |
10 |
10 |
10 |
10 |
|
equvalent to 10 mg |
|
|
|
|
|
|
|
Cross Povidone |
- |
- |
- |
30 |
35 |
40 |
|
Croscarmellose sodium |
30 |
35 |
40 |
- |
- |
- |
|
MCC |
55 |
55 |
55 |
55 |
55 |
55 |
|
Mannitol |
45 |
40 |
35 |
45 |
40 |
35 |
|
Mg stearate |
5 |
5 |
5 |
5 |
5 |
5 |
|
Talc |
5 |
5 |
5 |
5 |
5 |
5 |
|
Total Weight (mg) |
150 |
150 |
150 |
150 |
150 |
150 |
Experimental Data
1.Preformulation Studies
The following Preformulation studies were carried out for Glipizide and excipients;
2.Determination of melting point
A little amount of Glipizide was placed in a capillary tube that was sealed at one end to measure the melting point. The temperature at which the drug melts was measured using an electrically powered melting point equipment with the capillary tube within. After completing this three times, the average value was determined.
3.Drug-excipients compatibility studies
Practically every pharmaceutical dosege form included excipients as essential ingredients. The success rate of formulation and stability and effectiveness is depends on the selection of excipients. Which are added in formulation to protect it from degradation.
1.FT-IR Studies
2.DSC Studies
3.SEM studies
2.3.7. XRD of solid dispersion
2.3.8 Energy-dispersive X-ray analysis of solid dispersion
2.4-Preparation of Buffers and Reagents
2.4.1.Solution of sodium hydroxide (0.2 M)
In a 1000 ml volumetric flask with roughly 700 ml of distilled water, eight grams of sodium hydroxide were dissolved, and the volume was adjusted with distilled water.
1.3.1Potassium dihydrogen phosphate (0.2 M) solution
Potassium dihydrogen orthophosphate (27.218 gm) was dissolved in 1000 ml volumetric flask containing about 700 ml distilled water and volume was made up to the mark with distilled water. Phosphate buffer (pH 6.8) solution: Fifty ml of 0.2 M potassium dihydrogenorthophosphate solution was taken in a 500 ml volumetric flask, to which 22.4 ml of 0.2 M sodium hydroxide solution was added. Then volume was made up to the 200 ml with distilled water and pH was adjusted to 6.8 with dilute sodium hydroxide solution.
1.3.2.Hydrochloric acid (0.1 N) solution
Concentrated hydrochloric acid solution 8.5 ml was placed in 1000 ml volumetric flask containing about 700 ml distilled water and volume was made up to the mark with distilled water.
1.3.3Calibration curve of Glipizide
Appropriate aliquots were pipetted from the stock solution into various volumetric flasks, and contents were increased to 10 ml using 0.1 N hydrochloric acid solutions to provide drug concentrations of 2, 4, 6, 8, and 10 µg/ml.
pre-compression studys [5,6,7,8]
Melting point of drug
The melting point was determined by the capillary method and it was found to be in the range of 208°C -209°C which is the same as the standard reported melting point
2.1.1.1Angle of Repose
Using the cylinder method, the angle of repose of many powder mixed mixes made with different polymers was determined. The range of the angle of repose was determined to be 24.53° to 26.80°. Lower compressibility index values confirmed the granules' good flow ability, which was demonstrated by their angle of repose
2.1.1.1Hausner's Ratio
The calculation of Hausner's ratio for different powder mixed blends involves the utilization of both bulk density and tapped density data. It was discovered to be between 1.16 and 1.27. Every formulation demonstrates a workable flow characteristic.
2.1.2.1Bulk density
Using a cylinder, the bulk density of many powder blended blends was determined. It was discovered that the bulk density ranged from 0.63 to 0.71 gm/ml. The results are within the permissible range. The outcomes are shown
2.2.1.1Compressibility index (Carr’s Index)
In order to calculate the compressibility index of different powder blended, bulk density and tapped density data were used. It was discovered that Carr’s index ranged from 14.45 to 18.24%
Table no 2: Flow properties of granules preapred by different methods
|
Batch code |
Angle of repose(?) |
Bulk density (gm/cm3) |
Tapped density (gm/cm3) |
Hausner ratio (HR) |
?rr's index (CI) |
|
F1 |
26.74±0.21 |
0.63±0.01 |
0.89±0.01 |
1.22±0.050 |
18.24±0.056 |
|
F2 |
26.80±1.51 |
0.68±0.04 |
0.86±0.03 |
1.21±0.045 |
17.44±0.040 |
|
F3 |
25.89±0.37 |
0.70±0.03 |
0.82±0.02 |
1.19±0.038 |
15.04±0.030 |
|
F4 |
26.24±1.13 |
0.69±0.04 |
0.89±0.03 |
1.27±0.062 |
17.34±0.065 |
|
F5 |
26.20±0.52 |
0.70±0.04 |
0.82±0.02 |
1.20±0.029 |
16.45±0.020 |
|
F6 |
24.53±0.38 |
0.71±0.03 |
0.83±0.03 |
1.16±0.027 |
14.45±0.030 |
Post-compression study [9,10,11,12]
1.1.1Thickness
Using a Vernier Caliper, the formulation's thickness was measured. For every formulation, the measured thickness of the matrix tablets varied from 2.26 ± 0.16 mm to 3.40 ± 0.18 mm.
1.1.2Hardness
We examined the tablets using the Monsanto Hardness Tester. It was discovered that the tablets hardness ranged from 3.11 to 4.66 kg/cm?2;. Because the compression force was equal, uniform hardness was achieved.
1.1.3.Friability
Using a friabilator, the tablets' friability was examined and it was found to be within an acceptable range of 0.34% to 0.57%. and the hardness was appropriate
1.1.4.Weight variation
In the weight variation test, no tablet was found to differ from the mean value of tablets by a percentage that is permitted according to Indian Pharmacopoeia. It was discovered that the formulations met the requirements of the weight variation test.
1.1.4Content uniformity
The drug content was found among all formulation ranged from 77.12% to 95.28%. This supports the mixing was acceptable.
Table No: 3 Evaluation of physical parameters
|
Batch Code |
Weight variation average weight in (mg)±SD(n=10) |
Hardness (Kg/cm2) ±SD(n=3) |
Thickness (mm) ±SD(n=3) |
Friability (%) (n=10) |
Drug Content Uniformity (%)±SD(n=3) |
|
F1 |
99 ± 0.61 |
3.11 ± 0.28 |
2.26 ± 0.16 |
0.42 % |
77.12% |
|
F2 |
101 ± 1.14 |
3.45 ± 0.25 |
2.33 ± 0.19 |
0.34 % |
84.12% |
|
F3 |
100 ± 0.47 |
4.00 ± 0.28 |
3.27 ± 0.15 |
0.52 % |
89.93% |
|
F4 |
100 ± 0.47 |
3.16 ± 0.28 |
2.34 ± 0.08 |
0.47 % |
76.49% |
|
F5 |
100 ± 1.30 |
4.20 ± 0.39 |
3.10 ± 0.17 |
0.51% |
93.02% |
|
F6 |
100 ± 1.43 |
4.66 ± 0.55 |
3.40 ± 0.18 |
0.57% |
95.28% |
3.2.6Wetting time
The structure of tablets and hydrophobicity of excipients are intimately related to wetting. In every formulation, the wetting time was incredibly quick. This might be caused by both the ability to swell and the ability to absorb water. In every formulation, croscarmellose sodium, crospovidone, and MCC absorb water and exhibit quick wetting times. In contrast, all formulations of superdisintegrants containing crospovidone exhibit rapid wetting time.
Table no 4 Wetting time
|
Formulation Code |
Wetting Time (n=3) Mean ±SD (sec) |
|
F1 |
18 ±1.42 |
|
F2 |
22±1.69 |
|
F3 |
41±2.8 |
|
F4 |
73±1.35 |
|
F5 |
30±1.79 |
|
F6 |
29±1.30 |
3.2.7In vitro drug release
Table no 5 In vitro relese of drug
|
Time(min) |
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
|
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
10 |
19.95 |
20.05 |
21.30 |
20.96 |
21.05 |
22.03 |
|
20 |
35.27 |
36.79 |
38.70 |
37.62 |
37.56 |
39.21 |
|
30 |
53.48 |
55.95 |
59.61 |
56.35 |
58.89 |
60.47 |
|
40 |
59.83 |
64.69 |
71.20 |
65.51 |
69.76 |
72.34 |
|
50 |
60.4 |
68.54 |
81.32 |
68.47 |
75.92 |
83.21 |
|
60 |
68.30 |
78.54 |
90.54 |
73.65 |
85.34 |
92.74 |
Figure no 1 In vitro drug release
Glipizide drug was soluble in phosphate buffers and release depend on drug diffusion.One important element influencing the Immediate release was the polymer concentration in the tablet. Drug release was cumulative in formulations F1-68.3%, F2-78.54%, F3-69.46%, F4-87.65%, F5- 90.34% and F6-92.74% however, F6 formulation exhibited faster drug dissolution than the other formulations, releasing 92.74?ter 60 minutes.
FTIR of Glipizide + Kollidon (polymer)
Figure no 2 FTIR of Glipizide +Kollidon (Polymer)
FTIR spectra of optimized batch of solid dispersion showed pick in 649.45 representing C-H(stretch). The carbonyl group c=o (stetch) showed pick in 1156.40 representing C-N (stretch) N-H (stretch) at 3545.34.
SEM (Scanning Electron Microscope)
Figure no 3 SEM (Scanning Electron Microscope)
The Glipizide- Kollidon SD was observed as wide slices with a smooth surface and no small particles, according to the results of a scanning electron microscope. This serves as more evidence that the glipizide was soluble in the carrier and in its amorphous form. Generally speaking, powder flow decreases with decreasing particle size and increasing surface roughness. As a result, SEM pictures concurred with the AOR measurement results. The particle surfacemorphology is improved.
Differential Scanning Calorimetry (DSC)
Figure no.4 DSC of Glipizide+Kollidon(Polymer)
Diffraction scanning calorimetry thermogram is shown in figure.Glipizidfound to have a characteristics endothermic peak at 199° during DSC analysis. The Glipizide-Kollidon SD showed only an endothermic peak at 199°C. The result for the Glipizide – Kollidon mixture may have been due to interaction between Glipizide with higher melting point and Kollidon during heating process for DSC determination. The shifting forward endothermicpeak of Kollidon and the vanishing peak of Glipizide in the Glipizide -Kollidon SD suggested that Glipizide is completely soluble in the carrier and this result confirmed the miscibility of the Glipizide-Kollidon SD system.
1.2XRD of solid dispersion
Figure no 5 XRD of solid dispersion
Figure displays the XRD patterns of solid dispersion of drug the solid dispersion diffraction patters shows variations in the drug crystalline structure. The glipizide diffraction pattern shows highly crystalline structure as seen by multiple prominent peaks at an angle of [16°, 18°, 22°] a lower peak [10°, 20°]. A great deal of tiny peaks, suggesting that it was crystalline in nature. In the diffractogram of glipizide – Kollidon SD, the distinctive peak of glipizide vanished and was replaced by a flat diffraction peak. This suggested that glipizide’s crystalline shape had altered in SD and that it was totally soluble in kollidon. These findings suggested that the glipizide may be present in the glipizide – kollidon SD at a higher solubility and amorphous form, which would speed up the dissolution rate.
Energy-dispersive X-ray analysis of solid dispersion
Figure no 5 Energy-dispersive X-ray analysis of solid dispersion
Energy-dispersive X-ray spectroscopy is a valuable analytical technique for determining the elemental composition of materials, providing essential information for understanding their chemical makeup and properties. The specific elements present in the glipizide loaded kollidon 90F solid dispersion using energy-dispersive X-ray spectroscopy are carbon [C], which is fundamental element found in organic compound, including glipizide and kollidon polymer. Hydrogen [H] is another essential element found in the organic compounds, including glipizide and the kollidon, oxygen [O] is commonly present in organic molecules. Which may contain hydroxyl [-OH] groups. Nitrogen [N] was also present glipizide, which contains a pyrimidine ring & amino functional group that includes nitrogen atoms. Sulphur [S] is constituent of glipizide, as it contains a Sulphur atom as sulphamide in its chemical structure.
DISCUSSION
The current work aims to improve glipizide's solubility and dissolution in order to prepare it for use in immediate- release medication delivery systems. In this study, the solvent evaporation approach was successfully used to create a new SD of Glipizide using Kollidon 90F as the carrier. The Glipizide to Kollidon ratio of 1:3, generated by solvent evaporation method, demonstrated the maximum increment in saturated solubility and dissolution rate of Glipizide. Using appropriate polymers such as Kollidon 90F, in vitro dissolving study was conducted on a number of formulations. The results showed that F6 had the maximum drug release (92.74%) in 60 minutes. Using the solid dispersion approach, the solubility and dissolution of Glipizide were successfully increased in the current study. As a result, we may utilize Kollidon 90F as a carrier in solid dispersion, which has a wide range of application prospects for poorly soluble drugs. This investigation showed that utilizing Kollidon 90F significantly accelerated the dissolution and improved the bioavailability of glipizide.
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10.5281/zenodo.14580674
