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ORIGINAL ARTICLE
Year : 2013  |  Volume : 2  |  Issue : 1  |  Page : 2-8

Leucaena leucocephala and Trigonella foenum graceum mucilage in the design of fast disintegrating tablets


Department of Pharmaceutical Technology, H.K.E.S.'s Matoshree Taradevi Rampure Institute of Pharmaceutical Sciences, Gulbarga, Karnataka, India

Date of Web Publication17-Apr-2013

Correspondence Address:
Sidramappa B Shirsand
Department of Pharmaceutical Technology, H.K.E.S College of Pharmacy, Sedam road, Gulbarga - 585 104
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-344X.110557

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  Abstract 

Background: Glibenclamide is the second generation anti-diabetic drug used for the treatment of type 2 diabetes. Glibenclamide is practically insoluble in water, and possesses poor solubility, gastrointestinal absorption, and bioavailability. Aim: To prepare fast disintegrating tablets of glibenclamide in order to improve the dissolution rate and absorption. Materials and Methods: In this study, fast disintegrating tablets of glibenclamide were formulated with a view to enhance patient compliance by a direct compression method. In this method, mucilages of Leucaena leucocephala and Trigonella foenum-graceum were used as natural disintegrants and crospovidone as synthetic super disintegrant and directly compressible mannitol (Pearlitol SD 200) to enhance mouth feel. Results: The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, in vitro dispersion time, wetting time, water absorption ratio, in vitro drug release (in pH 6.8 phosphate buffer), stability studies (at 40°C/75% relative humidity for 3 months), and drug-excipients interaction (infra-red spectroscopy). Among all formulations, formulation (FG 3 ) containing 12% w/w of T. foenum-graceum was the overall best formulation (t50% = 8 min) based on the in vitro drug release characteristics as compared with the conventional commercial tablet formulation (t50% = 10 min). Stability studies on the formulation indicated that there are no significant changes in drug content and in vitro dispersion time (P < 0.05). Fourier transform-infra red studies revealed the integrity of the drug in the formulation. Conclusion: From the above work, it can be concluded that the fast disintegrating tablets of glibenclamide prepared using mucilage of L. leucocephala and T. foenum-graceum can be used as natural disintegrants for faster disintegration of tablets in mouth.

Keywords: Crospovidone, glibenclamide, Leucaena leucocephala, Mucilage of Trigonella foenum-graceum


How to cite this article:
Shirsand SB, Sagi PV, Holkunde RC, Pulgham VP. Leucaena leucocephala and Trigonella foenum graceum mucilage in the design of fast disintegrating tablets. Int J Health Allied Sci 2013;2:2-8

How to cite this URL:
Shirsand SB, Sagi PV, Holkunde RC, Pulgham VP. Leucaena leucocephala and Trigonella foenum graceum mucilage in the design of fast disintegrating tablets. Int J Health Allied Sci [serial online] 2013 [cited 2019 Aug 22];2:2-8. Available from: http://www.ijhas.in/text.asp?2013/2/1/2/110557


  Introduction Top


Oral route is the most convenient way of administering drugs, and among the oral dosage forms, tablets of different types are most common. Conventional tablets are popular because of their special properties such as suitability to self-administration, improved stability, accurate dosing, ease of handling, versatility with respect to type and dose of the drug, and suitability to scale up. [1] Despite all these advantages, conventional tablets generally do not prove very useful in following situations: Many elderly persons face difficulties in swallowing conventional oral tablets and capsules because of hand tremors and dysphagia. [2] Swallowing problem is also common among young individuals because of their underdeveloped muscular and nervous systems. [3],[4] Other groups that may experience problems using conventional oral dosage forms include mentally ill, developmentally disabled un-cooperative patients and reduced liquid plans, or those who are suffering from severe nausea. In some cases such as motion sickness, sudden episodes of allergic attack or coughing, and unavailability of drinking water, swallowing conventional tablets may be difficult. [5]

To overcome these problems, formulators have considerably dedicated their effort to develop a novel type of tablet dosage form (FDT) for oral administration, i.e., one which disintegrates/dissolves rapidly in saliva without drinking water. This tablet disintegrates instantaneously or disperses in the saliva. [4] Some drugs are absorbed from the mouth, pharynx, and esophagus as the saliva passes down into the stomach and produces rapid onset of action. In such cases, bioavailability of drug is significantly greater than those observed from the conventional tablet dosage form. [6],[7]

For all such cases, fast dissolving/disintegrating tablets (FD/DTs) preferably in the mouth are the perfect alternative. Their growing importance was underlined recently when European Pharmacopoeia adopted the term "Oro-dispersible Tablet" as the tablet that is to be placed in the mouth where it disperses rapidly before swallowing. [8] They are also called mouth dissolving tablets, melt-in-mouth tablets, rapimelts, porous tablets, oro-dispersible, quick dissolving, or rapidly disintegrating tablets. [1]

Recent advances in the novel drug delivery system (NDDS) aim to enhance safety and efficacy of drug molecules by formulating a convenient dosage form for administration and to achieve better patient compliance. One such approach is FD tablet of glibenclamide, an antidiabetic drug given by oral route in treatment of type 2 diabetes mellitus. [9] Glibenclamide is practically insoluble in water, possesses poor solubility, gastrointestinal absorption, and bioavailability. In order to improve the dissolution rate and absorption, FD tablets of glibenclamide were prepared.

Mucilage is most commonly used as an adjuvant in the manufacturing of different pharmaceutical dosage forms. They possess a variety of pharmaceutical properties, which include binding, disintegrating, suspending, emulsifying, and sustaining properties at different proportion in different pharmaceutical dosage forms. [10],[11],[12],[13] Traditionally used in medicine for its demulcent properties and serving as a cough suppressant, the synthetic polymers used as excipients suffer from many disadvantages such as high cost, toxicity, nonbiodegradability, and environmental pollution caused during their synthesis. Natural mucilages are preferred over semisynthetic and synthetic materials being nontoxic, low cost, freely available, and being emollient and nonirritating nature. [14],[15] The present work was performed to study the disintegrant property of Trigonella foenum-graceum and Leucaena leucocephala mucilage in comparison with crospovidone (CP) by formulating fast DTs of glibenclamide.


  Materials and Methods Top


Materials

Glibenclamide was a gift sample from Neon Pharmaceuticals, Mumbai. Crospovidone was a gift sample from Wockhardt Research Centre, Aurangabad. Micro-crystalline cellulose was a gift sample from Alkem Labs Private Limited, Mumbai. Directly compressible mannitol and sodium stearyl fumarate (SSF) were obtained as generous gifts from Strides Arco Labs, Bangalore. All the other chemicals used were of analytical grade.

Methods

Isolation of mucilage by the conventional method

For the isolation of mucilage seeds of plants, L. leucocephala and T. foenum-graceum seeds were soaked in distilled water for 48 h and then boiled for 1 h for complete release of mucilage into water. [16] The material was filtered by squeezing into a muslin cloth to remove marc. Then, equal volume of acetone was added to the filtrate to precipitate the mucilage. The mucilage was separated and dried in hot air oven at a <60°C, powdered (through #60 mesh), weighed, and stored in a desiccator until further use.

Formulations of glibenclamide FD tablets by the direct compression method

FD tablets of glibenclamide were prepared by the direct compression method using mucilage of L. leucocephala, T. foenum-graceum seeds as natural disintegrant, CP as a synthetic superdisintegrant in different ratios, and directly compressible mannitol as the diluent to enhance the mouth feel according to the formulae given in [Table 1]. [17] All ingredients were passed through #60 mesh separately. The drug and mannitol were mixed in small portions both each time, blended to get a uniform mixture, and kept aside. Then, the ingredients were weighed and mixed in geometrical order and tablets were compressed using 7-mm-round flat punches to get a tablet of 150 mg weight using a 10-station rotary tablet machine (Clit, Ahmadabad). A batch of 60 tablets was prepared for the designed formulations.
Table 1: Composition of formulations of glibenclamide fast dissolving tablets

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Evaluation of tablets

The prepared batches of tablets were evaluated for weight variation, thickness, tablet hardness, friability, drug content uniformity, in vitro dispersion time, in vitro drug release, and stability studies. [ 18],[19]

Weight variation

Twenty tablets were selected at random and weighed individually. The individual weights were compared with average weights for determination of weight variation.

Tablet thickness

Thickness of the tablet is important for uniformity of tablet size. Thickness was measured using vernier calipers. It was determined by checking the thickness of three tablets of each formulation.

Tablet hardness

The resistance of tablets to chipping or breakage under the conditions of storage, transportation, and handling before usage depends on its hardness. The hardness of each batch of tablet was checked using a digital hardness tester. The hardness was measured in terms of kg/cm 2 . Randomly, three tablets were selected and tested for hardness. The average hardness of three determinations was recorded.

Friability

Friability generally refers to loss in weight of tablets in the containers due to removal of fines from the tablet surface. Friability generally reflects poor cohesion of tablet ingredients. Ten tablets were weighed, their initial weights were recorded, they were placed in the Roche friabilator and rotated at the speed of 25 rpm for 100 revolutions. Then, the tablets were removed from the friabilator, dusted off the fines, and weighed again; the final weight was recorded.

Percentage friability was calculated by using the following formula:



Drug content uniformity

At random, 10 tablets were weighed and powdered from each batch. The powder equivalent to 5 mg of the drug was weighed accurately and dissolved in 25 mL of methanol. The solution was shaken thoroughly. The undissolved matter was removed by filtration through Whattman No. 41 filter paper. Dilutions were made to obtain a solution of 10 μg/mL. The absorbance of the diluted solutions was measured at 229 nm using a UV spectrophotometer. The concentration of the drug was computed from the standard curve of the glibenclamide in methanol.

Wetting time and water absorption ratio

A piece of tissue paper, folded twice, was placed in a small petri-dish containing 6 mL of water. [ 20] A tablet was put on the paper and the time required for complete wetting was measured. The wetted tablet was then weighed.

Water absorption ratio "R" was determined using following equation:

R = 100 × (Wa - Wb )/Wa ,

where Wa is the eight of the tablet after water absorption and Wb = weight of the tablet before water absorption.

In vitro dispersion time

A tablet was added to 10 mL of phosphate buffer solution, pH 6.8, at 37 ± 0.5°C. Time required for complete dispersion of a tablet was measured. [21]

In vitro dissolution study

In vitro dissolution of glibenclamide FDT was studied in a USP XXII type-II dissolution apparatus (Electro Lab model TDT06N) employing a paddle stirrer at 50 rpm using 900 mL pH 6.8 phosphate buffer at 37 ± 0.5°C as the dissolution medium, one tablet was used in each test. [22] Five milliliters of the sample of dissolution medium were withdrawn by means of a syringe fitted with a prefilter at known intervals of time and analyzed for drug release by measuring the absorbance at 229 nm. The volume withdrawn at each time interval was replaced with fresh quantity of dissolution medium and the cumulative percentage of glibenclamide released was calculated and plotted against time.

Accelerated stability studies on promising glibenclamide formulations

Stability studies on the promising formulations (FG 3 and FCP 3 ) were performed by storing 15 tablets in an amber-colored screw-capped bottle at elevated temperatures of 40 ± 2°C/75 ± 5% relative humidity (Stability chamber, Oswald) over a period 90 days (3 months). At the interval of 1 month, the tablets were visually examined for any physical changes, percentage drug content, and in vitro dispersion time.

Drug-excipients interaction studies

Infra red (IR) spectra of glibenclamide and its formulation were obtained by the KBr pellets method using a Shimadzu FTIR series (Model 8400S) spectrophotometer in order to rule out drug carrier interactions.


  Results and Discussion Top


In present research work, FDT of glibenclamide were prepared by the direct compression method, employing natural disintegrants such as mucilage of T. foenum-graceum and L. leucocephala and then compared with CP as a synthetic superdisintegrant in different ratios and mannitol as a diluent to enhance the mouth feel. Ten formulations with a control formulation FC 0 (without superdisintegrant) were designed. The tablets were evaluated for various physicochemical parameters, and the blends were also evaluated for various precompression parameters. These blends displayed angle of repose and Carr's index values of <28° and <16% indicating good flow properties of the blends prepared.

The tablets prepared were of uniform weight (due to uniform die fill) with acceptable variation as per Indian Pharmacopoeia specification i.e., <±7.5%. The weight variation values were as shown in [Table 2]. The hardness of tablets was found to be 2.6-2.9 kg/cm 2 , indicating that there is no significant variation in hardness of all the formulations and the values are as shown in [Table 2]. Friability values of prepared tablets were found to be <1% (an indication of good mechanical resistance of tablets) and the values were shown in [Table 2]. Drug content was found to be 90-110%, which is within acceptable limits. Drug content values were as shown in [Table 2].
Table 2: Postcompression parameters of formulations of glibenclamide

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Water absorption ratio and wetting time that are important criteria for understanding capacity of disintegrant to swell in the presence of little amount of water were found to be 71.02-87.70% and 15.66-58.06 s, respectively, and were as shown in [Table 2]. Among all of the designed formulations, FG 3 and FCP 3 were found to be promising and displayed an in vitro dispersion time ranging from 12.98 to 47.79 s, which facilitated their faster dispersion in mouth (as shown in [Table 2]). Formulation FG 3 containing 12% w/w of T. foenum-graceum was found to be promising and showed an in vitro dispersion time of 24.8 s, wetting time of 29.79 s, and water absorption ratio 71.02% as compared with its conventional commercial formulation. The experimental data also revealed that the results obtained from the T. foenum-graceum mucilage are comparable with those of conventional commercial formulation and even slightly better than those of conventional commercial formulations.

In vitro dissolution studies on the promising formulations (FG 3 and FCP 3 ), control (FC 0 ), and CCF were performed in pH 6.8 phosphate buffer. The various dissolution parameter values, namely percentage drug dissolved in 30 min (D30 min ), dissolution efficiency [23] at 10 min (DE 10 ), t50% , t70% , and t90% are shown in [Table 3] and the dissolution profile is depicted in [Figure 1]. These data reveal that overall formulation FG 3 showed faster drug release (t50% = 8 min) than CCF (t50% = 10 min) tablet formulation of glibenclamide.
Table 3: Comparative in vitro dissolution parameters of promising fast dissolving tablet formulations, control, and commercial conventional formulation in pH 6.8 phosphate buffer

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Figure 1: Comparative cumulative drug release versus time plots (zero‑order) of promising fast dissolving tablet formulations, control and conventional commercial formulations in pH 6.8 phosphate buffer

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Stability studies of the above formulation presented in [Table 4] indicated that there are no significant changes in physical appearance, drug content, and in vitro dispersion time at the end of 3-month period (P < 0.05). Statistical analysis for drug content data of promising formulations FLe 3, FG 3 , and FCP 3 showed promising results and are shown in [Table 5]. IR spectroscopic studies indicated that the drug is compatible with all excipients. The IR spectrum of glibenclamide pure drug and promising formulations is shown in [Figure 2]. The IR spectrum of FG 3 and FCP 3 showed all the characteristics peaks of glibenclamide pure drug, thus conforming that no drug-excipients interaction occurred within the ormulations [Table 6] and [Table 7].
Table 4: Stability data of FG3, FLe3, and FCP3 formulation at 40°C/75% relative humidity

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Table 5: Statistical analysis for drug content data of formulations FLe3, FG3, and FCP3

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Table 6: Statistical analysis for drug content data of FG3 formulation

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Table 7: Statistical analysis for drug content data of FCP3 formulation

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Figure 2: IR spectrum of glibenclamide and promising formulations

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  Conclusion Top


The following points can be concluded from this study performed on fast DTs of glibenclamide:

  • The blends prepared using mucilage of L. leucocephala, T. foenum-graceum as natural disintegrants, and CP as the synthetic super disintegrant have shown good flow properties.
  • Tablets prepared by the direct compression method were found to be good without any defects, i.e., chipping, capping, and sticking.
  • As the concentration of mucilage (natural disintegrant) and CP (super disintegrant) increased in the formulation, the water absorption ratio increased and the wetting time decreased, resulting in faster in vitro dispersion of the tablet formulations.
  • Based on the in vitro dispersion time, formulation FG 3 was found to be promising and displayed in vitro dispersion time of approximately 24.8 s and wetting time of 29.79 s, whereas formulation FCP 3 displayed in vitro dispersion time of approximately 12.98 s and wetting time of 15.66 s, which facilitated faster dispersion in the mouth.
  • The promising formulations FG 3 and FCP 3 displayed good water absorption ratio that indicates better and faster swelling ability of the disintegrants in the presence of little amount of water.
  • The promising formulation FG 3 (t50% = 8 min) showed faster drug release as compared to the conventional commercial formulation (t50% = 10 min).


From the above, it can be concluded that the fast DTs of glibenclamide formulated using mucilage L. leucocephala and T. foenum-graceum as natural disintegrants have advantages such as oral safety and low cost.

 
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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