Journal of Advanced Pharmaceutical Technology & Research

ORIGINAL ARTICLE
Year
: 2022  |  Volume : 13  |  Issue : 4  |  Page : 252--260

Formulation and characterization of orodispersible tablet of glimepiride


Ahmad AB Yosef Kinani, Hassanien Sagban Taghi 
 Pharmaceutical Department, College of Pharmacy, Al-Farahidi University, Baghdad, Iraq

Correspondence Address:
Dr. Ahmad AB Yosef Kinani
Pharmaceutical Department, College of Pharmacy, Al-Farahidi University, Baghdad
Iraq

Abstract

The present study is regarding, Glimepiride is one derivatives of sulfonyl urea used in the treatment of Type II DM which classified as class-II (BCS) of high permeability and low degree of solubility. The endeavor is to improve its solubility by solvent vaporization method to enhance the rate of dissolution of glimepiride. Soluplus (Polyvinyl caprolactampolyvinyl acetate-polyethylene glycol graft co-polymer) , PVP k40 (Polyvinylpyrrolidone) and PEG k5 are blended with the drug in various proportions (1:1,1:3) and prepared Soluplus1, Soluplus2, PEG1, PEG2, PVP1 and PVP2 as solid dispersion. The optimized formula of solid dispersion PVP1 is added to sodium starch glycolate and cross-carmellose. The disintegration profile will appear diminished in the drug release from the dosage form at a determined period of time. Differential scanning calorimetry appeared to a reduction in its crystallinity in solid dispersions. Scanning electron microscope and particle size analysis show a reduction in the drug particle size as solid dispersions. Fourier transform infrared spectroscopy does not show an interaction between them. Hence, that PVP1 batch will be considered from nine oral dissolving tablets dosage form. Finally, orally disintegrating tablets are estimated for various parameters; for instance, disintegration time, the content of the drug, wetting time, and in vitro release profile show a conventional result. The selected formula F6 shows a good result in disintegration time during 13-second and in-vitro drug release profile achieves 96% at the end of 40 minutes.



How to cite this article:
Kinani AA, Taghi HS. Formulation and characterization of orodispersible tablet of glimepiride.J Adv Pharm Technol Res 2022;13:252-260


How to cite this URL:
Kinani AA, Taghi HS. Formulation and characterization of orodispersible tablet of glimepiride. J Adv Pharm Technol Res [serial online] 2022 [cited 2022 Nov 28 ];13:252-260
Available from: https://www.japtr.org/text.asp?2022/13/4/252/358213


Full Text



 Introduction



Orodispersible tablets (ODTs) are important in the pharmaceutical formulation for both over-the-counter drugs and prescription; they improve patient acceptability, low cost and simple methods. The disintegration of such dosage form is determined by the size and hardness of tablets.[1] Thus the goal of current study is to compress the component into tablet that characterized by fast dissolving through rapid disintegration and high drug release from the formula during a short period of time.[2] It is also considered as a single dose solid dispersion that used orally inside the mouth cavity, which dissolves in saliva with rapid onset of action. ODTs are produced by adding cross-povidone, sodium cross-carmellose, and sodium starch-glycolate.[3] There are different techniques used in the production of ODTs like lyophilization, mass extrusion, spray drying, molding, sublimation, and direct compression.[4]

The preparation of solid dispersion relies on the disintegration rate which can be enhanced by improve surface area to avoid the precipitation within the carrier, solid including in the solution and improve the wetting properties due to direct interaction with hydrophilic polymer carrier, to take a shape of a metastable crystalline structure.[5] Therefore adjusting the drug/polymer ratio and selecting the suitable method have direct effect on the type of solid dispersion and drug release behavior [6]

The polyethylene glycol (PEG) 5k, Soluplus, and polyvinylpyrrolidone (PVP) 40k are the foremost utilized polymer to carry solid dispersion and their capability to form atomic adduct compounds.[7] The presence of hydroxyl and carbonyl group tends to enhance water solubility, bioavailability, and stability.[8] Hence, the use of such polymers has a crucial role in improving the dissolution rate profile for the drug and consequently the absorption.[9] Glimepiride has low water solubility (<0.004 mg/ml) and dissolution properties may cause poor bioavailability.[10] Additionally, Glimepiride is a weak acid (pKa 6.2), and has low solubility in acidic media, so it is a challenge to overcome this issue by formulating Glimepiride as ODTs to obtain rapid release of the drug in the oral cavity with a few second to achieve a high percent of drug release from the formula.[11] Subsequently, to improve the therapeutic efficacy by enhancement of solubility and dissolution rate of Glimepiride.[12]

 Materials and Methods



Materials

Glimepiride was a gift from Al Warqaa Medical Store for Chemicals Baghdad and Soluplus, PVP 40k, and PEG 5k were purchased from Al-Noor Medical Store for Chemicals. Sodium starch glycolate and sodium croscarmellose are purchased from Al-Noor Medical store.

Method of preparation

Solvent evaporation technique was used in the preparation of glimepiride solid dispersion, where various formulas of glimepiride were prepared by solid dispersion technique and arranged into two proportions with each polymer PEG 5k, PVP 40k, and Soluplus. Precisely weighed amount of the drug with polymer; then homogenously mixed with an adequate volume of alcohol. The prepared solution was evaporated at room temperature to get dry solid dispersion at that point dried in a desiccator; the batches of solid dispersion are shown in [Table 1]. The yield solid was sieved through 65 meshes to ensure the equal consistency of particle size within the required range.[13]{Table 1}

Estimation of solid dispersion

Taking 10mg of prepared Glimepiride/polymer solid dispersion of (1:1 and 1:3) ratio and dilute with 50mL Ethanol of 95% using magnetic stirred for 1-hour then scanning at 217nm UV absorbance to obtain λmax as shown in [Figure 1] UV.[14] Then performing the solubility study, percentage yield, FTIR Spectroscopy, In-vitro study, scanning electron microscopy and thermal analysis (differential scanning calorimetry) to estimate the formulation of solid dispersion that assist in the selection of the optimize formula.[15]{Figure 1}

Preparation of orally disintegrating tablets

Glimepiride ODTs are prepared by combination of Na-starch glycolate and super-Na-crosscarmellose through direct compression method. The component are accurately weighed and passed through 50# sieve prior blending and placed into a glass mortar to mix consistently as shown in [Table 2] the component of Glimepiride ODTs formula. The blend at that point is estimated for precompression parameters before the compression process.[16]{Table 2}

Estimation of precompression powder

The characterization study is performed by determining the angle of repose, tapped and bulk density, Carr's Index and Hausner ratio; to estimate the properties of the blend before compression.[17]

Estimation of orally disintegrating tablets

Weight variation test is carried out for the prepared tablets to determine the total differences in weight. The percentage of weight variation is obtained by taking the total weight of 20 tablets and the average weight difference with mean value of ±S.D.[18]

The hardness test was performed to determine the driving force required to break the tablet over an applied pressure. The hardness was obtained in kg about 3–5 kg/cm2, which is palatable for uncoated tablets. The hardness test device was Monsanto hardness analyzer.[19]

Friability test is performed to determine the weight loss from the tablet and comparing the final weight with the original tablet. This test is important obtain the surface resistance during the packaging and transport. The device used is Roche Friabilator.[20]

Dissolution time analysis

The dissolution test apparatus type II USP was used to determine the rate of dissolution of the ODTs.[21] One tablet was set in each vessel of 1 liter 0.1 M HCL at 37 ± 2°C, and the sample is scanned at 217nm UV to obtain the average percent of drug release during 25-minute.[25]

Wetting test

The test was used to determine the wetting time by placing a tablet in a beaker; Each table should be weighted before and after fluid absorption to determine the difference in weight using sensitive electronic balance to obtain the percent of wetting according to the equation 1.[23]

R = Wa - Wd / Wd × 100

Where Wa is tablet after water after and Wd is dry tablet.

In vitro study

The study was conducted in vitro to determine the drug release profile in phosphate-buffered saline (PBS) of pH 7 for 25.[24] Eight samples are tested triplicate using dissolution test apparatus type II (Digital DT 950 Series Dissolution Tester); the tablet is placed in 900mL phosphate buffer solution at 37±2°C and the sample is scanned at 217nm UV to obtain the average percent of drug release during 25-minute.[25]

 Results and Discussion



Solvent evaporation method is used to produce Glimepiride ODTs and the preformulation studies are performed for all the formula to obtain the data of organoleptic properties, angle of repose, Carr's 48. index, solubility analysis, λmax and calibration curve; which assist in the selection of best formula.

Preformulation studies

Characterization: Organoleptic properties were studied and are placed in [Table 3].{Table 3}

λ max determination

UV spectrophotometer is used to determine λmax of the drug in different solvents as shown in [Figure 1]; the data of λmax in ethanol, water and PBS are placed in [Table 4].{Table 4}

Calibration curve determination

The solution of 0.1mg/mL Glimepiride shows linear relation at maximum UV absorption, the data of the intercept, slope and R2 are placed in [Table 5]; and the calibration curve of Glimepiride in PBS, water and ethanol are shown in [Figure 2], [Figure 3], [Figure 4].{Table 5}{Figure 2}{Figure 3}{Figure 4}

Fourier transform infrared spectroscopy spectroscopy

The characterizations of Glimepiride are appeared in [Table 6]. The data of wave numbers of Glimepiride are placed [Table 7]. FTIR stretching of C=O group at 1656-1715cm-1 and stretching of C-H bond at 2922cm-1 ; which slightly shifted in batch PEG1 ,PEG2 ,PVP1, PVP2,Soluplus1 and Soluplus2 at 2954, 2873,2837, 2886, 2939, 2933 cm-1 respectively. The boarded peak indicates a great interaction of H- bonds with PEG1, PVP1and Soluplus1 which cause a shift into the amorphous form; thus there is no change in the internal structure due to the compatibility of drug and polymers. FTIR analysis for Glimepiride, PVP1, PVP2, PEG1, PEG2, Soluplus 1 and Soluplus 2 are shown in [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10] respectively.{Table 6}{Table 7}{Figure 5}{Figure 6}{Figure 7}{Figure 8}{Figure 9}{Figure 10}

Saturated solubility of Glimepiride/Solid-dispersion

Solubility study is performed to enhance the bioavailability of poor water solubility drug.[19],[20] Here, glimepiride solubility is compared with polymers solubility in water as shown in [Figure 11] where the polymers appear higher solubility in water. The solid dispersion of PVP1 and PVP2 have higher solubility than other batches due to formation of H-bonds with water to form amorphous structure to improve the drug release. The data of saturated solubility are recorded in [Table 5] with mean value of ±S.D.{Figure 11}

Percentage yield and drug content of the formulas

The obtained data of drug content and percentage yield by detecting the amount of drug in each formula using UV absorbance at 217nm where Soluplus 2 was the higher drug content than others because of the stuck nature of the polymer as shown in [Table 8].{Table 8}

In vitro study

The drug release in PBS alone is 53.13% within 10 min, while with polymer PVP K-40 the percent of release profile increased to 73.4% and 58.2% for PVP1 and PVP2, respectively [Figure 12].{Figure 12}

Thermal study differential scanning calorimetry

The test is important to determine the compatibility between the drug and excipients to obtain an accurate data about their interactions.

Interpretation of DSC thermograms data is shown in [Figure 13], [Figure 14], [Figure 15], [Figure 16] for pure drug, PVP1, PEG1 and S1 respectively below, the information about melting point shows a decline in PVP1 with less M. P than pure drug; 75.3°C and 191.8°C that's mean the endothermic reaction of the formula PVP1 with reduction in the temperature of the thermograms peak area; that gives an indication in the faster dissolution rate because of the reduction in crystallinity and rapid dissolving, when compared with a pure drug, on the other hand, there is the same change in the thermograms shows in [Figure 13], [Figure 14], [Figure 15], [Figure 16]; show a reduction in M. P of Soluplus 1 as compared to the unadulterated Glimepiride likely due to diminish in the size crystillinty. The melting point of formula Soluplus 1 and PEG1 is found to be 174.23°C and 168.17°C. The inhibition in crystallinity is ascribed to interaction drug particles with polymer matrix through using the solvent evaporation technique which gives a result about the compatibility of both together.{Figure 13}{Figure 14}{Figure 15}{Figure 16}

Estimation of orally disintegrating tablets formulas

Study of precompression parameters

[Table 9] shows the results of precompression parameters of compression technique in the presence of super disintegrant at various ratios. The reduction in size of granules and angle of repose can improve the flowability and increase in the surface area; the data have determined with mean value of ±S.D.{Table 9}

Estimation of glimepiride orally disintegrating tablets

The obtained data of ODTs are shown in [Table 10]; the thickness ranges between 2.23±0.45 to 3.88±0.24 mm, the less the thickness shows a good product quality. The hardness test is not more than 4.00 ± 0.200 kg/cm2 for accepted range. Weight variation is within the accepted limit of 248 ± 1.030–252 ± 1.23 mg. The friability values for all formulas are less than 1.0% which fall in range of 0.37%-0.78% and have good mechanical strength. [Table 11] illustrates the values for the estimation study.{Table 10}{Table 11}

The disintegration time for all formulas is ranged between 13 to 22 seconds, F6 shows the rapid disintegration time within 13 seconds.

[Figure 17] shows water absorption of the ODTs. The data have determined with mean value of ±S.D., percentage of drug release from 28 to 44% for F6 as shown in [Table 11].{Figure 17}

In vitro orally disintegrating tablets release profile

[Figure 18] illustrates the Release profile in-vitro study by using dissolution rate apparatus USP2 test to obtain the dissolution time for the ODTs in PBS 7 media at 37°C, for F6 about 69% after 10 minutes and maximum release achieved 95.3% after 40 minutes; [Figure 18] illustrates the release profile, while the remaining formulas the burst release is started after 10 minutes less than 40% and the maximum release after 40 minutes is less than 90% as shown in [Table 12].{Figure 18}{Table 12}

 Conclusion



Glimepiride ODT is prepared by using direct compression method as solid dispersion in the presence of super-disintegrant to enhance the dissolution rate of the tablets in oral cavity and increase the drug release profile through initial burst release from the matrix due to the swelling of the polymer in the presence of fluid to disintegrate the ODTs with a few second. The selection of F6 as a best formula is based on the collected data regarding high drug content and rapid drug release from the formula.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Zhang L, Yang J, Chen XQ, Zan K, Wen XD, Chen H, et al. Antidiabetic and antioxidant effects of extracts from Potentilla discolor Bunge on diabetic rats induced by high fat diet and streptozotocin. J Ethnopharmacol 2010;132:518-24.
2Mythili MD, Vyas R, Akila G, Gunasekaran S. Effect of streptozotocin on the ultrastructure of rat pancreatic islets. Microsc Res Tech 2004;63:274-81.
3Kohli A, Verma S Jr., Sharma A Jr. Psychogenic polydipsia. Indian J Psychiatry 2011;53:166-7.
4Morgenthaler NG, Struck J, Alonso C, Bergmann A. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem 2006;52:112-9.
5Kamiyama T, Iseki K, Kawazoe N, Takishita S, Fukiyama K. Carbamazepine-induced hyponatremia in a patient with partial central diabetes insipidus. Nephron 1993;64:142-5.
6Thompson P Jr., Earll JM, Schaaf M. Comparison of clofibrate and chlorpropamide in vasopressin-responsive diabetes insipidus. Metabolism 1977;26:749-62.
7Conceição J, Adeoye O, Cabral-Marques H, Concheiro A, Alvarez-Lorenzo C, Lobo JM. Orodispersible carbamazepine/hydroxypropyl-β-cyclodextrin tablets obtained by direct compression with five-in-one co-processed excipients. AAPS Pharm Sci Tech 2020;21:39.
8Koner JS, Rajabi-Siahboomi AR, Missaghi S, Kirby DJ, Perrie Y, Ahmed J, et al. Conceptualisation, development, fabrication and in vivo validation of a novel disintegration tester for orally disintegrating tablets. Sci Rep 2019;9:12467-9.
9Matsui R, Uchida S, Namiki N. Combination effect of physical and gustatory taste masking for propiverine hydrochloride orally disintegrating tablets on palatability. Biol Pharm Bull 2015;38:17-22.
10Alshehri SM, Park JB, Alsulays BB, Tiwari RV, Almutairy B, Alshetaili AS, et al. Mefenamic acid taste-masked oral disintegrating tablets with enhanced solubility via molecular interaction produced by hot melt extrusion technology. J Drug Deliv Sci Technol 2015;27:18-27.
11Kukulka M, Nudurupati S, Perez MC. Bioavailability, safety, and pharmacodynamics of delayed-release dexlansoprazole administered as two 30 mg orally disintegrating tablets or one 60 mg capsule. Therap Adv Gastroenterol 2016;9:770-80.
12Szymańska-Chargot M, Cybulska J, Zdunek A. Sensing the structural differences in cellulose from apple and bacterial cell wall materials by Raman and FT-IR spectroscopy. Sensors (Basel) 2011;11:5543-60.
13Daniel MC, Astruc D. Gold nanoparticles: Assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem Rev 2004;104:293-346.
14Gill P, Ghalami M, Ghaemi A, Mosavari N, Abdul-Tehrani H, Sadeghizadeh M. Nanodiagnostic method for colorimetric detection of Mycobacterium tuberculosis 16S rRNA. Nanobiotechnol 2008;4:28-35.
15Blagden N, de Matas M, Gavan PT, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev 2007;59:617-30.
16Kumar A, Sahoo SK, Padhee K, Kochar PS, Sathapathy A, Pathak N. Review on solubility enhancement techniques for hydrophobic drugs. Pharm Glob 2011;3:001-7.
17Tambe A, Mokashi P, Pandita N. Ex-vivo intestinal absorption study of boswellic acid, cyclodextrin complexes and poloxamer solid dispersions using everted gut sac technique. J Pharm Biomed Anal 2019;167:66-73.
18Muller RH, Jacobs C, Kayer O. Nanosuspension for formulation of poorly soluble drugs. In: Nielloud F, Marti-Mesters G, editors. Pharmaceutical Emulsion and Suspension. New York: Marcel Dekker; 2000. p. 383-407.
19Lipinski CA. Avoiding investment in doomed drugs, is poor solubility an industry wide problem? Curr Drugs Dis 2001;4:17-9.
20Sekiguchi K, Obi N. Studies on absorption of eutectic mixtures. I.A comparison of the behavior of eutectic mixtures of sulphathiazoleand that of ordinary sulphathiazole in man. Chem Pharm Bull 1961;9:866-72.
21Topaloğlu Y, Yener G, Gönüllü U. Inclusion of ketoprofen with skimmed milk by freeze-drying. Farmaco 1999;54:648-52.
22Ishikawa T, Watanabe Y, Utoguchi N, Matsumoto M. Preparation and evaluation of tablets rapidly disintegrating in saliva containing bitter-taste-masked granules by the compression method. Chem Pharm Bull (Tokyo) 1999;47:1451-4.
23Lindenberg M, Kopp S, Dressman JR. Classification of orally administered drugs on the world health organization model list of essential medicines according to the biopharmaceutical classification system. Eur J Pharm Biopharm 2004;58:265-78.
24Bredenberg S, Duberg M, Lennernäs B, Lennernäs H, Pettersson A, Westerberg M, et al. In vitro and in vivo evaluation of a new sublingual tablet system for rapid oromucosal absorption using fentanyl citrate as the active substance. Eur J Pharm Sci 2003;20:327-34.
25Gole D, Savall T, Ma LF, Greenwood D, Wilkinson P, Davies, J. (2005). U.S. Patent Application No. 10/638,822.