Extraction and Evaluation of Linseed Mucilage as Binding Agent in Prednisolone Tablet 20 mg

Alaa Balla Suliman Abuelrakha*, Elnazeer I. Hamedelniel

1 Faculty of Pharmacy, University of Omdurman Islamic (OIU), P.O. Box 382 Omdurman, Sudan

Received: 06-Dec-2018 , Accepted: 16-Jan-2019

Keywords: Extraction, Evaluation, Linseed, mucilage, Binding agent

DOI: http://dx.doi.org/10.20510/ukjpb/7/i1/179296

 

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Abstract

Great interest been have develop to discover new excipients to solve problem that faced us during formulation like incompatibility and compressibility that lead to slow down manufacturing processes. Linseed mucilage has properties that suggested it as useful additives and binding agent like inertness, nontoxic and viscosity. The purpose of the present study was to extract and evaluate linseed mucilage as binding agent in prednisolone tablets. The Linseed mucilage was extracted and evaluated for physicochemical properties using official procedures. Tablet was prepared by wet granulation. Granules evaluation revealed satisfactory results. Three formula were prepared that contain three different percent from linseed mucilage 3%, 5% and 7%.The hardness test result show great increase in tablet hardness 4.23, 5.59 and 7.76, respectively. The dissolution test was carried in Ph 1.2 for 2 hours and cumulative drug release 20.33%, 17.88% and 14.49% respectively .And at Ph 6.8 for 4 hours cumulative drug release 78.18%, 75.43% and 69.19%. The tablets formulated showed acceptable general appearance. Formula mucilage 7% showed the best flowbility of granules, hardness and friability when compared with formulas 3% and 5%.In weight variation test indicated that the type and concentration of mucilage used were not significant. When increase the percent of mucilage in formula combined with increase in tablet hardness. Invitro dissolution study indicated that the main factors which influence the amount of drug released were the pH of the medium used and concentration of the mucilage.

1 Introduction

Solid dosage prepared with aid of suitable additives dependent on intended use and method of manufacture. Examples of excipients that can be used fillers, binders, disintegrants and lubricants¹. There are many types of binders from natural source or synthetics. Added to drug mixture to insure granules and tablets can be formed with the required strength.They can be added in the form of powder in dry granulation method or in liquid in wet granulation method it included in formulation in low concentrations typically 2%-10% by weight2.

Factors related to drug or related to other additives used in the formulation or related to the binders its self influence the strength and friability of granules and tablets, example of that particles size that effect granules strength and porosity and solubility of drug and excipients in granulations solvent³ also mechanical and film forming behaviors affect the strength and binder matrix4.

The application of polymers in pharmaceuticals sciences growing greatly in the field of drug delivery system and control of drug release and that because of unique properties which have not attained by other materials5. There are two type of polymers synthetics and natural, natural polymers have advantage of been environmental friendly processing, biodegradable, nontoxic, better patient tolerance, from edible source and low cost6.

Mucilage is most commonly used excipient in pharmaceutical preparations has high molecular weight, sticky and gummy substance; they are esters of sulphoric acid which is a polysacharide7.There are two methods of mucilage isolations hot and cold, in cold method seed soaked in distilled water for 5 hours and then boiled for 30 min and allowed to settled, acetone was added in the same volume after marc removing to precipitate the mucilage, separated and dried in oven , sieved and stored in desiccators. Hot method plant is soaked for twelve hour in distilled water and crushed in blender for fifteen min the dispersion is boiled for thirty min and passed through eight fold muslin cloth8.9.

Mucilage have a variety of application as tablet binder, disintegrant, emulsifiers, suspending agent, gelling agent, stabilizing agent, thickening agent, film forming agent, and as sustain agent in matrix tablet10.

Linseed Mucilage extracted from the seed of Linumusitatissimumfrom the family Linaceae, varieties grown for fibers are tall, little branched and early maturing and those for seed are not tall, more branched and high seed yield11, linseed mucilage evaluated as a release retardant of drug matrix tablet in some studies 12.

Prednisolone is glucocorticoids act by inhibiting leukocyte infiltration at the site of inflammation, used for the treatment of adrenocortical insufficiency and rheumatoid arthritis13.

The development of new tablet binder to achieve the optimum quality of the tablet,  the objective of this study starting by extracting linseed mucilage, prepare the tablet using three different concentrations of the mucilage and then tablet evaluations.

2 Materials and Methods

Materials are illustrated in table 1.

2.1 Extraction of linseed mucilage

The linseeds were washed with water to remove dirt`s and debris, seeds were powdered and soaked in water for six hour, boiled for forty five min and left stand for one hour to allow complete release of mucilage into water, the mucilage was extracted using multilayer muslin cloth bag to remove the marc from the solution, acetone (in the volumes of three times to the volume of filtrate) was added to precipitate the mucilage, the mucilage was separated, dried, in an oven at 40°c collected, sieved and stored14.

2.2 Physiochemical properties of mucilage

Physiochemical properties such as swelling index, pH, bulk density, tapped density, Hausners ratio, compressibility index and angle of repose were determined according to official procedures 12.

2.3 Pre-compression parameters

The powder blend was evaluated by determination of bulk density, tapped density, angle of repose, compressibility index and Hausner ratio according to the BP guidelines.

2.4 Preparation of the tablet

The tablets were prepared by wet granulation method, prednisolone, linseed mucilage and MCC were mixed together and the mixture was passed through mech(no.60), granulation was done using a sufficient amount of distilled water the wet mass passed through mesh (no.35) and mixed with magnesium state and talc, tablets were compressed using single rotary tablet press (lab press-1/Shakti pharmatech Pvt Ltd).

Three different formulas having different concentrations of linseed mucilage (3%, 5% and 7% w/w) were developed and total tablet weight 200mg.the composition of the designed formulations were showed in Table 2.

2.5 Evaluation of the tablets                           

All tablets were evaluated for following different parameters which include15

2.5.1 General appearance

Five tablets from different batches were randomly selected and organoleptic properties such as color, odor and shape were evaluated.

2.5.2 Hardness test

Hardness indicate the ability of a tablet to withstand shocks will handling, the hardness of the tablets were determined using Erweka hardness tester, it was expressed in kg/cm2, ten tablets were randomly picked from each formuland hardness of the tables wasdetermined.

2.5.3 Weight variation test

Randomly twenty tablets were selected after compression weighed individually and average was determined.

2.5.4 Friability test

Friability of the tablets was determined using Roche Friabilator. This device subjects the tablets to the combined effect of abrasion and shock in a plastic chamber revolving at 25 rpm and dropping the tablets at a height of 6 inches in each revolution. Pre weighed sample of ten tablets was placed in the friabilator for 4 minutes. Tablets were de dusted using a soft wiper and re weighed.

The friability (f) is given by the formula:

Friability (f) = 100 (Wo -W) / Wo

Where Wo is weight of the tablets before the test and W is the weight of the tablet after the test.

2.5.5 Disintegration test

The disintegration test was performed in a BP Basket rack assembly using 1000ml pH 6.8 phosphate buffer maintained at 37±0.5°C.

2.5.6 Swelling index

The extent of swelling was measured in terms of % weight gain by the tablet. The swelling behavior of formulations F1, F2 and F3 were studied. One tablet from each formulation was kept in a Petri dish containing pH 6.8 phosphate buffer  at the end of 2 h, 4 h and 6 h, kept on tissue paper and weighed and the process was continued till the end of 24 h, the percent weight gain by the tablet was calculated by formula:

S.I = {(Wt-W0) / W0} X 100

Where; S.I = swelling index, Wt = weight of tablet at time (t), Wo = weight of tablet at time t = 0

2.5.7 In vitro drug release studies

Release of Prednisolne from the formulated  tablets was studied in phosphate buffer of pH 6.8 and acidic buffer 1.2 (900ml) using a United State Pharmacopoeia (USP) 6- station Dissolution Rate Test Apparatus with a rotating paddle stirrer at 50 rpm and 37° ± 0.5°C as prescribed for Prednisolone tablets in USP14. Prednisolone analyzed by UV spectrophotometer at 247 nm15.

3 Results and Discussion

3.1 Extraction of Linseed mucilage

The average yield of dried mucilage obtained from linseeds was 31% w/w, the mucilage obtained was yellowish brown color powder and mucilage identified by giving positive results to Rutheinium test16.

3.2 Physiochemical properties of the mucilage

The mucilage studied for its swelling behavior in distilled water in buffer in pH 6.8 and generally the swelling index calculated indicated that the mucilage can act well as binding agent17. Compressibility index, Hausner ratio and Angle of ripose showed good flowability that enhances the quality of manufacturing processes2 (Table 3).

3.3 Pre-compression parameters

Prednisolone granules were prepared by wet granulation method using distilled water in sufficient quantity and evaluated for it physical characterization before compression. The Angle of repose results showed excellent flow, the compressibility index was found to be in the range of 10.3% to 13.8% and the Hausner ratio in the range of 1.1 to 1.16 indicating very good flowability2 (Table 4).

3.4 Evaluation of the tablets

3.4.1 General appearance

Prednisolone tablets were very pale white in color, smooth, and flat shaped in appearance.

3.4.2 Hardness test

Tablet hardness increased follows mucilage percent increasing in the formulation. Table 5 and figure 1 shows the results.

3.4.3 Weight variation

Average weight was determined and stander deviations and tablet mean calculated, none of the tablets deviated from the average weight by more than ±5 according to USP (Table 6).

3.4.4 Friability test

Test of friability was carried in ten tablets from each formula, the result can help to predict that those tablets can withstand other manufacturing process need to be conducted1 (Table 7).

3.4.5 Disintegration test

The tablet disintegrated toke time to disintegrate but it reserved it shape as granules not turn into fine powder (Table 8).

3.4.6 Swelling index

The swelling behavior of all formulation was studied showed the swelling characteristics of linseed mucilage containing tablets; the swelling index was calculated with respect to time, as time increases, the swelling index was increased (Fig 2).

3.4.7 Dissolution test result

Dissolution test results of the tablet formulated in acidic media pH1.2 showed  percent of release 14.49% ,17.88% and 20.33% for f1, f2 1nd f3 respectively in dissolution time two hours. Table8 showed the percentage of release.

The dissolution behavior of the tablet in pH 6.8 presented in table 9 and Figure 3

Further studies must be conducted for different concentrations of the linseed mucilage in different pH medium and carry stability study.

4 Conclusions

The tablets formulations showed acceptable general appearance, formula mucilage 7% showed the best flowability of granules, hardness and friability when compared with formulas 3% and 5%.

In weight variation test indicated that the type and concentration of mucilage used were not significant. Increasing the percent of the mucilage in the formula lead to increase the hardness of the tablet.The tablets swelling index increased when mucilage concentrations were increased.

5 Acknowledgement

Thanks and praise be to Allah to complete this work and prayers and peace be upon the prophet Muhammad peace be upon him.

I extend my profound gratitude to my able supervisor Dr. Elnazeer I. Hamedelniel for his support on the manner and how this research work came to be.

Sincerely my limitless gratitude goes to the family Of Omdurman Islamic University for their relentless support.

6 Competing Interests

Authors have declared that no competing interests exist.

7 Author’s contributions

ABS carried out the study, interpreted the results, and prepared the manuscript. EIM participated in the design of the study and was responsible for its coordination and contributed in the preparation of the manuscript. All authors read and approved the final manuscript.

8 References

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