Evaluation of Binding Property of Remusatia vivipara (Roxb) Mucilage in Tablet Formulation

Mayur R. Bhurat^1,2*and Dr. S. D. Barhate¹

¹Shree Sureshdada Jain Institute of Pharmaceutical Education and Research, Jammer

²J.J.T. University, Zunzunu, Rajasthan

*Corresponding Author E-mail: _{bhuratmayur@gmail.com}

ABSTRACT:

Remusatia vivipara is a common herbaceous belongs to the family of Araceae. Tubers of plant contain mucilage hence attempt to evaluate the tubers for suitability as tablet binder is considered and the present investigation repots the isolation of mucilage of Remusatia vivipara tubers. The DSC and FTIR thermograms of drug and mucilage indicated no chemical interaction. Phytochemical and Physiochemical characteristics of mucilage were studied which confirmed the mucilage nature. The mucilage was evaluated for its granulating and binding properties in compressed tablet using Metformin HCl as model drug. The granules prepared by mucilage with different concentration such as 1%, 3%, 5% and 10% were compared with starch paste, which was used as standard binder. The tablets had good physiochemical properties and the drug release was more than 95% within 24hr. It was observed that decreasing the concentration of mucilage increases hardness and the disintegration time. The tablet prepared using 1% and 3% shows drug release rate in sustained manner and that of standard binder 10% starch paste used for comparison. Remusatia vivipara mucilage could be used as a good binding agent at very low concentrations. This can be used for sustaining the drug release from tablets, since the prepared tablets produced a sticky film of hydration on the surface, which ultimately reduces drug release rate and hence it can be evaluated for its efficacy to sustain the drug release.

KEY WORDS: Remusatia vivipara, Mucilage, Binder.

INTRODUCTION:

Medicinal plants constitute main source of new pharmaceuticals and healthcare products. The family Araceae, commonly known as aroids consists of 105 genera and more than 3300 species. (Bhurat M. R. et al., 2011) Excipients are the additives used to convert active pharmaceutical ingredients into pharmaceutical dosage form suitable for administration to patients (Kibbe A.H., et al., 2000). New and improved excipients continue to be developed to meet the needs of conventional drug delivery systems and to meet the needs of advanced tablet manufacturing. Mucilage and gums have been known since ancient times for their medicinal uses. In the modern era also they widely used in pharmaceutical industries as tablet binders, emulsions and thickeners in cosmetics and suspensions as film-forming agents and traditional colloids (Monif T., et al.,1992, Kapoor V.P., etal., 1992).

Hence the demand for these substances is increasing and new sources are getting tapped (Kakrani H.K., et al., 1981, Bhunvara N.S., et al., 1985). Though, India, due to geographical and environmental positioning has traditionally been a good source for such products among the Asian countries, a large quantity of this still being imported from the European countries to meet up the ever- increasing demand (Kulkarni G. T., et al., 2002).

Remusatia vivipara Roxb. Family Araceae is terrestrial herb with fleshy subglobose tubers. The plant has been used medicinally for anti inflammatory, analgesic, antioxidant, depressant etc. (Bhura M. R. et al., 2011, D. Asha et al., 2013, Bhurat M. R., 2011) In the present study an effort was made to extract the mucilage from the tubers of Remusatia vivipara Roxb. Family Araceae and investigate the pharmaceutical properties of the mucilage to assess its suitability as an excipient in the pharmaceutical formulation. Here the potential binding capacity of the mucilage has been evaluated with the standard starch paste as a tablet binder.

Materials and Method Plant Procurement and Authentication of plants

The plant was collected from Toranmal, Dist. Nandurbar in the month of October. The plant was authenticated by Dr. Tanvir A. Khan, Department of Botany, M. J. College, Jalgaon, Maharashtra.

Materials

Metformin hydrochloride obtained as gift sample from Lupin pharmaceuticals, Aurangabad. Mucilage extracted from tubers and talc, magnesium. stearate, lactose obtained as gift sample from In care pharmaceuticals, Aurangabad.

Extraction Methodology

The tubers are separated from plant and then tubers are washed and clean with water. Then tubers are then cut into slices then dried in sunlight and then grind it to convert it into powder form.

Isolation of mucilage:

The tubers of Remusatia vivipara(100gm) were soaked in distilled water for 24 hour, boiled for 1 hour and kept aside for 2 hour to release mucilage in to water. The material was squeezed in a muslin bag to remove the marc from the filtrate. Then, equal volume of acetone was added to filtrate to precipitate the mucilage. The mucilage was separated, dried in oven at temperature less than 50°C, powdered and passed through sieve number 80. The powder was stored in desiccator until further use. (Trease G.E.et al., 2003)

Purification of mucilage:

The mucilage is purified by shaking in beaker on shaker with Ethanol. Percentage yield was Found to be 30.02%.

Evaluation of mucilage for flow properties

The mucilage was evaluated for flow properties using Tapped density, Bulk density, Angle of repose, Hausner’s ratio, Carr’s index.It was found to be good to flow.( Martin A.et al.,2008) It was calculated by following formulae-1) Tapped density=Mass/Tapped volume 2) Bulk density= Mass/volume 3) Angle of repose (ø) =1/tan h/r4) Hausner’s ratio= Tapped density/ Bulk density 5) Carr’s index= Tapped density- Bulk density/ Tapped density.

Preparation of granules

Lactose and starch powder were passed through sieve No: 40. Metformin IP was mixed with lactose and starch powder and was homogeneously dry-mixed. The granules prepared by wet granulation method using Remusatia vivipara mucilage and starch binders in concentration of 1%, 3%,5% and 10%. the moistened friable mass was passed through sieve No: 16 and granules were dried at 50°C for 30 min. the dried granules were re-sieved through sieve No: 20.(I.P., 1996, Martin A.et al., 2008)

Evaluation of granules for flow properties

The granules were evaluated for flow properties using Tapped density. Bulk density, Angle of repose, Hausner’s ratio, Carr’s index. It was found to be good to flow. (Martin A.et al., 2008) It was calculated as above mentioned in evaluation of mucilage.

Preparation of tablets

Magnesium stearate and talc were mixed with prepared granules. This uniformly mixed blend was compressed into 300 mg tablets using flat face round tooling on a Jaguar rotary tablet machine by using RVM as 1%, 3%, 5% , 10% & S.P.. The tablets were stored in tightly closed glass container and evaluated for following parameters. (Martin A.et al., 2008, I.P., 1996)

Evaluation of prepared tablets

Compressed tablets were then evaluated for shape, diameter and thickness, weight variation, disintegration, hardness, friability study. Diameter and thickness were measured by using Vernier Caliper. Hardness was measured by Monsanto type hardness tester. Friability was determined in friabilator (Electrolab EF-2, USP). For disintegration test, one tablet was placed in each tube of disintegration apparatus (Electrolab ED-2L, USP) and the test was carried out using distilled water as a disintegrating media.(I.P., 1996)

In Vitro Dissolution Studies

Release of Metformin from the tablets was studied using a six basket IP I dissolution apparatus taking 900 ml of phosphate buffer (pH 6.8) for 24 h. The dissolution media were maintained at a temperature of 37±0.5°C.The speed of rotation of basket was maintained at 50 rpm. The basket was covered with 100 mesh nylon cloth to prevent the escape of the beads. The samples were withdrawn at specified intervals. The samples were filtered by Whatman filter paper No.41 and suitably diluted to determine the absorbance at 233 nm using UV/ Visible single-beam spectrophotometer (Electrolab, Mumbai, India). The in vitro dissolution rates were further tested using pharmacokinetic models. The % of drug released vs. time (zero order release plot) was shown in fig. (I.P.1996)

Drug-excipient compatibility and FTIR studies

This study has been done to check whether there is any compatibility related problems are associated with drug and excipients used for the formulation of tablet. The drug and excipients must be compatible with one another to produce a product that is stable, efficacious, attractive and easy to administer and safe. If the excipients are new and not been used in formulations containing the active substance, the compatibility studies are of paramount importance. Thermal analysis and FTIR can be used to investigate and predict any physicochemical interactions between components in a formulation and can therefore be applied to the selection of suitable chemically compatible excipients. (Beckett A.H.et al., 2004, Sharma Y.R.et al., 2009). The IR spectral analysis of a drug and other excipients were taken using Press pellet technique (using KBr). The IR spectra’s were determined by using Shimadzu 8400S, USA FTIR (Beckett A.H.et al., 2004, Sharma Y.R.et al., 2009)

Table No.1

Sr. no.	Ingredients	RVM 1%	RVM 3%	RVM 5%	RVM 10%	Std S.P. 10%
1	Metformin	150mg	150mg	150mg	150mg	150mg
2	RVM	3gm	9mg	15mg	30mg	-
3	Powder Starch	20mg	20mg	20mg	20mg	20mg
4	Lactose	115mg	109mg	103mg	88mg	88mg
5	Talc	6mg	6mg	6mg	6mg	6mg
6	Magnesium Stearate	6mg	6mg	6mg	6mg	6mg
7	Starch Paste	-	-	-	-	30mg
8	Total Weight	300mg	300mg	300mg	300mg	300mg

Differential Scanning Calorimeter Studies (DSC)

DSC was performed on a Shimadzu DSC-60 (Shimadzu Limited Japan). A 1:1 ratio of drug and excipient was weighed into aluminum crucible and sample was analyzed by heating at a scanning rate of 100C/min over a temperature range 200-3000C under a nitrogen flow of 40ml/ min. Reproducibility was checked by running the sample in triplicate18.( Beckett A.H.et al.,2004, Sharma Y.R.et al.,2009)

Formulation of tablets

Tablets were formulated with different concentration of mucilage as 1%, 3%, 5%, 10% and S.P. and other excipients are given in table 1.

Phytochemical analysis

The presence of carbohydrate and mucilage was substantiated with the positive result upon the treatment with Molisch’s Test (formation of purple color) and Ruthenium red test (formation of pink color on powdered particles), respectively.

Flow Property of Mucilage

By studying various parameters for flow property it was found that mucilage is good to flow and values are shown in table 2.

Table.2 - Flow Property of Mucilage

Sr .No.	Properties	Values
1	Bulk density g/cm3	0.62±0.01
2	Tapped density g/cm3	0.74±0.03
3	Carr’s index (%)	15.18±1.67
4	Hausner’s ratio	1.26±0.09
5	Angle of repose	25.99±1.82

All values are expressed in mean. (n=3)

Flow Property of Prepared Granules

By studying various parameters for flow property it was found that granules is good to flow and values are shown in table 3.

Table .3 Flow properties of prepared granules

Sr .No.	Properties	Values
1	Bulk density g/cm3	0.60±0.02
2	Tapped density g/cm3	0.71±0.03
3	Carr’s index (%)	14.98±1.35
4	Hausner’s ratio	1.11±0.05
5	Angle of repose	24.40±1.60

All values are expressed in mean. (n=3)

Evaluation of tablets

After studying the chemical-chemical interaction the mucilage was selected as tablet binder in the formulation of Metformine tablets, and the tablets were formulated with various percentages of this mucilage. The standard binder starch paste was also used for the comparison study (Table-4). The physical tests for all the formulated tablets were shown in Table-4. All the batches of tablets exhibited the diameter and thickness, uniformity in weight, hardness and friability values were within the pharmacopoeial limits.

In-vitro release study

The in-vitro dissolution profile of with different concentrations of Remusatia vivipara mucilage and Starch paste is shown in Figure. (Figure no.1) It was found that release of drug from tablet using RVM is extended as compared to tablet using starch paste. Also found that as concentration of mucilage is increased the release of drug is also extends. Table no. 5 shows the % drug release drug with different concentration of mucilage and starch paste used as standard for comparison.

Name of the Drug = Metformin

Loading Dose in mg = 150mg

Volume of Dissolution Medium (ml) = 900

Volume of Sample removed (ml) = 1

Dilution Factor = 10

Table No.4 - Comparison of evaluation of formulated Metformin tablets using RVM and starch binders (SP)

Formulations	Diameter (mm)	Thickness (mm)	Weight Variation (mg)	Disintegration Time (min)	Hardness (Kg/cm)	Friability %±SD
RVM 1%	9±0.1256	4±0.1798	300.1±0.0163	41±0.89	4±0.2840	0.6±0.29
RVM 3%	9±0.1389	4±0.1814	299.5±0.0178	32±0.32	4±0.3211	0.5±0.07
RVM 5%	9±0.1651	4±0.1428	301.3±0.0398	30±0.55	4±0.4512	0.4±0.12
RVM 10%	9±0.1421	4±0.0934	301.2±0.0772	24±0.49	4±0.2431	0.5 ±0.08
STD. S.P. 10%	9±0.1181	4±0.1054	299.9±0.1643	23±0.34	4±0.1298	0.5 ±0.11

All values are expressed in mean. (n=3)

% DRUG RELEASE

Fig. No. 1- Comparison of In vitro drug release from tablets prepared using different concentration of RVM and Std. Starch Paste

Figure No.2 - IR analysis of Metformin

Figure No.3 - IR analysis of RVM and Metformin

Table No. 5- Comparative effects of different concentration levels of Remusatia vivipara mucilage and Standard Starch Paste used as the binding agents on the release rate of Metformin tablets

TIME (HOUR)	RVM 1%	RVM 3%	RVM 5%	RVM 10%	STD.S.P. 10%
0	0.00	0.00	0.00	0.00	0.00
0.5	39.522	43.993	31.869	32.155	40.592
1	43.411	46.239	34.361	33.578	66.939
2	50.180	57.104	44.635	42.827	73.411
4	53.564	62.553	50.178	47.883	78.792
6	67.195	63.829	57.088	57.566	82.951
8	72.375	76.351	72.041	63.736	92.672
10	80.006	82.208	80.346	74.599	95.683
12	87.00	91.347	84.696	78.236	99.407
14	93.00	94.291	87.805	83.687	-
16	97.086	98.273	95.463	87.334	-
18	99.430	98.381	96.430	90.274	-
20	-	-	-	94.348	-
22	-	-	-	95.452	-
24	-	-	-	96.555	-

All values are expressed in mean. (n=3)

CONCLUSION:

As per Pharmacopoeia, It was found that the tablets prepared using 1%,3%,5% & 10% w/ v concentration of Isolated Remusatia vivipara mucilage passes disintegration test, hardness test and other evaluation tests for tablets. The formulations have enough hardness to withstand the mechanical shocks of handling in manufacturing and packing. Taking all the above parameters into consideration, the study has revealed a good potential of Remusatia vivipara mucilage as a binder for conventional tablet formulations. From the present investigation, it can be concluded that the mucilage of Remusatia vivipara can be used in low concentration as a binder in comparison with standard binder. The results suggested that RVM could be a potential binder in low concentration level. It can also be used for sustaining the drug release from tablets at lower concentration. Also from In vitro dissolution profile it is conclude that tablets prepared using RVM 10% shows extended release of drug as compared to tablets prepared using starch paste of same strength as standard binder. From this study it is conclude that tablet prepared with 10% RVM shows extended drug release that is for 24 hours as compared to 10% standard S.P which for 12 hours.

REFERENCES:

1. Bhurat M. R., Sapakale H. S., Salunkhe K.G., Sanghavi R. S., Kawatikwar P.S., Asian Journal of Biochemical and Pharmaceutical Research 2011a, 2, 303-306.

2. Bhurat M.R.; Bagad Y.M.; Waghmare R.U.; Wankhede U.W.; Salunkhe P.S., IJPS’s Journal of Pharmacology and Toxicology 2011b, 1, 61-66.

3. Bhurat M. R., International Journal of Current Pharmaceutical Research , Vol 3, issue 1, 2011.

4. D. Asha, M. S. Nalini and M. D. Shylaja† Scholars Research Library Der Pharmacia Lettre, 2013, 5 (5):120-128

5. Monif. T, Mahlhtra AK. Kapoor VP. Indian J. Pharm Sci 1992; 54: 234-240. 3. Kapoor VP, Banerji R, Prakash D. J SciInd Res 1992; 51:1-22.

6. Kakrani HK, Jain NK. Indian J Hosp Pharm 1981; 100-102.

7. Bhunvara NS, Khorana ML. Indian Drugs 1985; 22:500-502.

8. Kulkarni. GT, Gowthamarajan K, Rao BG, Suresh. B. Indian Drugs 2002, 38, 422-468.

9. Kulkarni G.T. Gowthamarajan K. Rao B.G. and Suesh B., Evaluation of binding properties of Plantago ovata and Trigonella foenumgraecum mucilages, Indian drugs, 2002, 39(8), 422-425.

10. Sharma Y.R., Element organic Spectroscopy, 4^th edition, Chand S Publication: New Delhi, 2009, 132-133.

11. Beckett A.H. and Stenlake J.B., Practical Pharmaceutical chemistry, Part 2. CBS Publication: New Delhi, 2004, 383-389.

12. Indian Pharmacopeia, Ministry of health and family welfare, New Delhi, 1996, 2, 710,711, A- 89,A-95, A-114-115, A-80.

13. Aulton M.E., Powder flow, In: Pharmaceutics-The design and manufacture of medicines. London New York: Churchill Livingstone, 2007, 176.

14. Martin A. Swarbrick J. and Cammarata A., Micromeritics, In: Physical Pharmacy and Pharmaceutical Sciences, 5th edition, New Delhi: Wolters Kluwer publication, 2008, 492.

15. Khandelwal. K.R, Nirali Prakashan, Practical Pharmacognosy, Techniques and Experiments, 2002, 9th edition, pp 149-156.

16. Evaluation of honey locust (GleditsiatriacanthosLinn.) gum as sustaining material in tablet dosage forms, Melike Üner, Turan Altýnkurt Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Beyazýt, Istanbul 34119, Turkey, Elsevier Publication, April 2004.

17. Trease G.E. and Evans W.C., “Pharmacognosy”, William and Wilkins Co., Baltimore, USA, 14th Ed, 2003 P-349,351.

18. Kokate C.K., “Practical Pharmacognosy”, 3rd Ed, Vallabh Prakashan, Delhi, 1991, PP-107-109.

19. Mukarjee P., “Quality Control of Herbal Drugs”, 1st Ed, Business horizon, New Delhi, 2002, PP- 370-381.

20. Anroop, B., Bhatnagar, S.P., Ghosh, B., Parcha, V., 2005. Studies on Ocimum grattisimum seed mucilage: evaluation of suspending properties. Ind. J. Pharm. Sci. 67, 206–209.

21. Baveja, S.K., Rangarao, K.V., Jagdish, A., 1998. Examination of natural gums and mucilages as sustaining materials in tablet dosage forms. Ind. J. Pharm. Sci. 50, 89–92.

22. Monif, T., Malhotra, A.K., Kapoor, V.P., 1992. Cassia fissula seed galactomanan: potential binding agent for pharmaceutical formulation. Ind. J. Pharm. Sci. 54, 234–240.

23. Girish K Jani, Dhiren P Shah, Vipul D Prajapati, Vineet C Jain, Gums and mucilages: versatile excipients for pharmaceutical formulations, Asian Journal of Pharmaceutical Sciences 2009, 4 (5): 309-323

24. Kibbe AH, editor. Handbook of Pharmaceutical Excipient. London (UK); The Pharmaceutical Press: 2000, 3, 43-55.

25. King’s American Dispensatory, 1898.

26. http://www.henriettesherbal.com/

Received on 21.11.2014 Accepted on 11.01.2015

Asian J. Pharm. Tech. 2015; Vol. 5: Issue 1, Pg 23-28

DOI: 10.5958/2231-5713.2015.00005.7