Research J. Pharm. and Tech. 1(4): Oct.-Dec.

2008, ,

ISSN 0974-3618

www.rjptonline.org

RESEARCH ARTICLE

Design, Development and In-vitro Evaluation of Sustain Release Rubia cordifolia Matrix Tablet.
NM Bhopale*, PB Aswar, NB Banarase and SS Khadabadi
Government College of Pharmacy, Amravati 444 604 (MS) India *Corresponding Author E-mail: nileshbhopale@yahoo.co.in

ABSTRACT:
The purpose of the present investigation was to develop the sustained release matrix tablet of Rubia cordifolia using the various polymers like HPMC (Hydroxy-Propyl-methyl-cellulose), Ethyl cellulose, of different viscosity grade. Tablet formulations were developed using wet granulation method. Water extract of Rubia cordifolia was used. Addition of different diluents like lactose, magnesium stearate and cab-o-sil were used for improving flowability and compressibility. Binder such as polyvinyl pyrrolidone was used for optimization of the formulations. Sodium starch glycolate was used as disintegrating agent. Pre and post formulation parameters were studied for all the batches. HPMC KM4 shows better result for matrix tablet in terms of sustained drug release with comparison to different viscosity grade of HPMC and ethyl cellulose. The dissolution study, of the Rubia cordifolia tablets exhibited 99.54% release of total polyphenol.

KEY WORDS: Rubia cordifolia extract, matrix released tablet, HPMC, Ethyl cellulose INTRODUCTION:
Inflammation is a key feature in autoimmune disease. Inflammation occurs as the immune system reacts to injury, infection, environmental agents, malignancy, and cellular changes. In skin, inflammation is most visible because it causes noticeable swelling, redness, discomfort and pain. The process leading to inflammation, which is known as the inflammatory response, also induces changes that aren't seen but influence the effects of inflammation and their severity. Rubia cordifolia used traditionally in Ayurvedic medicine to alleviate symptoms of chronic rheumatic inflammation which acts by inhibiting the lipoxygenase pathway and production of cumene hydroperoxides 2. Various marketed formulations containing Rubia cordifolia extract include Cystone tablet, Rumalaya tablet, and Septilin tablet, etc. They are available in conventional dosage forms which are prone to various problems like fluctuation in drug blood level, patients inconvenience, etc. These problems can be overcome by formulating sustained release matrix tablet using Rubia cordifolia extract. UV Spectrophotometer (Shimadzu) and tablet punching machine (Rimek minipress) were used for the present study. Rubia cordifolia was obtained from local sources and authenticated by Dr. Prabha Y. Bhogaonkar (Director, Government Vidarbha Institute of Science and Humanities, Amravati). Rubia cordifolia root was extracted by using water as solvent. Preliminary physicochemical parameters and photochemical test of the Rubia cordifolia extract (Table no.1, 2) were carried out. Same extract was used for the formulation. The total polyphenol in extract was estimated by Folin Ciocalteu method using UV Spectrophotometer 3. Formulations of Rubia cordifolia extract 4: Tablets of Rubia cordifolia extract were prepared by wet granulation method. PVP-K30 (10%) and sodium starch glycolate was added as binder and disintegrating agent respectively. for the preparation of matrix tablet various viscosity grades of HPMC and ethyl cellulose were used (Table no.3). The extract, lactose and the polymer were passed through 60# sieve and then granulated using PVP K-30 in isopropyl alcohol as granulating agent, the wet mass was passed through 8# sieve. Granules were air dried for one hour and dried granules were passed through 16# sieve. These granules were lubricated in poly bag using talc and cab-o-sil. Desired quantity of granules were weighed and fed manually to compression machine. The flat faced

MATERIAL AND METHODS:

HPMC (K4M, K15M, K100M), Ethyl cellulose (75cps, 100cps), and PVP (K30) were purchased from Loba chem. (Mumbai, India). All other chemical used were of analytical grade. Received on 13.09.2008 Accepted on 15.10.2008 Modified on 30.10.2008 RJPT All right reserved

Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008;Page 475-477

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punch i.e. upper punch with break line and plane lower punch of diameter 10 mm was used for compression.
Table 1- Result of physical constants Parameters of physical constant 1) Total Ash 2) Acid insoluble ash 3) Water soluble Ash 4) Moisture content % w/w 6.9 % 4.065 % 5.6 % 13.25 %

RESULTS AND DISCUSSION:

Phytochemical study shows presence of carbohydrates, glycosides, anthraquinone, saponin glycosides, tannins and phenolics, mucilage and fixed oil. (Table no. 1,). Extractive values such as water soluble extractive value was found to be 10.26% and alcohol soluble extractive value was found 6.6%. Ash values such as total ash, acid insoluble ash, and water soluble ash were found to be 6.9%, 4.065 %, 5.6 % respectively. Moisture content was found to be 13.25%. Total polyphenol content was found to be 41.55%.
Table 3- Results of phytochemical tests. Sr. No. Chemical tests performed 1. Carbohydrates Proteins 2. Amino acids 3. Glycosides 4. I)anthraquinone Ii)cardiac Iii)coumarins Iv)cyanogenetic Saponin glycosides 5. Alkaloids: 6. Flavonoids: 7. Steroids and Triterpenoids: 8. Tannins and Phenolics 9. Mucilage: 10. Gums: 11. Fixed oil 12. Volatile oil 13. WE + + + + + + + -

Table 2- Extractive values of different solvents, with percentage Extractability and color of extract Extract Extractive value % Colour of extract Water soluble 10.26 % Reddish black extractive Alcohol soluble 6.6 % Reddish black extractive

Evaluation of rubia cordifolia tablet 5: The tablets of rubia cordifolia extract prepared by wet granulation were evaluated for preformulation and post formulation parameters. Angle of repose, total porosity, Carrs index, bulk density, tap density, friability, weight variation, hardness, disintegration were measured. (Table no.4) Fig. 1- In vitro release profile of all formulations showing sustained effect for twelve hours.
overlain dissolution profile of all 6 formulation 120 % released of drug 100 80 60 40 20 0 0 5 time 10 15 Series1 Series2 Series3 Series4 Series5 Series6

Since, polyphenol constitute are major chemical entity in Rubia cordifolia, we thought it logical to evaluate our formulation with respect to total polyphenol content. Polyphenol content can be taken as a reliable and reproducible parameter for the dissolution study of the Rubia cordifolia formulation. From the dissolution study (table no 6) it was found that HPMC K4M shows better drug release, as compared to other polymers. In the current research work an attempt was made to formulate a matrix tablet of Rubia cordifolia Extract. From the results it can be concluded that, the matrix tablet prepared using extracts of Rubia cordifolia is found to be a novel one. Sustained release matrix tablets of Rubia cordifolia were prepared successfully using ethyl cellulose and hydroxyl propyl methyl cellulose as release retarding polymers by wet granulation method. Various evaluation parameter for the granules like bulk density, tap density, angle of repose, total porosity and Carrs index suggest that granules has good flow property. Various evaluation parameters for tablets like thickness, hardness, friability and disintegration of all formulations were found to be satisfactory. In case of formulations containing HPMC, viscosity was a major factor affecting the drug release. An

In-Vitro dissolution study of rubia cordifolia tablet 6: The in vitro release of total polyphenol from formulation batches was carried out in 0.1N HCl for 2 hours and continued in pH 6.8 phosphate buffer for remaining 10 hours. The studies were performed using USP dissolution apparatus II at 37 0.5 C and 50 rpm. Samples were taken at interval of one hour each and analyzed for drug content at 765 nm by Using UV- Spectrophotometer. Dissolution study was carried out for each 6 tablet per batch for 12 hours and drug release study was carried out on the basis of total polyphenol contents. Since, polyphenol constitutes the major chemical entity in Rubia cordifolia; we thought it logical to evaluate our formulation with respect to total polyphenol content. With respect to total polyphenol contents present in extract, the drug release study was carried out. The results of dissolution study were given in table no. 5.

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inverse relationship existed between polymer viscosity and drug release; thus higher the polymer viscosity lower was the drug release. From stability studies (as per ICH guidelines) no significant change was observed in stability of optimized formulation batches.
Table 4- Formulation table showing composition of each matrix tablet using various different polymers. Formulation F1 F2 F3 F4 F5 F6 code. Ingredients (mg) Extract of rubia 250 250 250 250 250 250 cordifolia HPMC-K-M4 32 HPMC-K-M15 32 HPMC-K-100M 32 E.C-75cps 30 E.C-100cps 30 S.S.G 12 12 12 12 12 12 PVP-K-30 40 40 40 40 40 40 TALC 10 10 10 10 10 10 CAB-O-SIL 10 10 10 10 10 10 LACTOSE 46 46 46 46 46 77 Tablet weight (mg) 400 400 400 400 400 400 Table 5-Evaluation parameters of granules. Parame Loose Tapped Carrs Angle ters bulk bulk index of Formula density density (I) Repose tions (LBD) (TBD) () F1 0.506 0.589 14.89 37.44 + 0.02 +0.036 +0.95 +0.12 0.337+ 14.53 37.02 F2 0.290 0.04 +0.05 +0.01 +0.03 0.351 11.95 37.72 F3 0.306 +0.019 +0.33 +0.43 +0.02 F4 0.290 0.338 14.35 36.56 +0.04 +0.032 +0.14 +0.01 F5 0.309 0.354 13.11 35.75 +0.04 +0.023 +0.89 +1.68 0.579 12.14 36.89 F6 0.509 +0.002 +0.008 +0.94 +0.58

CONCLUSION:
Present research work deals with the formulation and evaluation of matrix tablet. Rubia cordifolia root were purchased from the local market of Nagpur. Dr. Prabha Y. Bhogaonkar, Director, Vidarbha Institute of Science and Humanities had done the authentication of Rubia cordifolia Linn. Various Physical parameters like, Total ash, Water soluble ash, Acid insoluble ash, LOD, Water soluble extractive value, Alcohol soluble extractive value, of Rubia cordifolia were determined. Various qualitative tests for inorganic elements like Aluminum, Chloride, Copper etc. were determined. Aqueous extract of root was prepared and this extract was tested for presence of various Phytochemicals like Carbohydrates, Proteins, Alkaloids, Glycosides, etc. Formulations were prepared by using aqueous extract of Rubia cordifolia and various sustained release polymers. The granules were prepared by using Wet granulation method and evaluated for various parameters i.e. Bulk density, % Compressibility index, Angle of repose and Total porosity. These granules were then compressed into tablet and evaluated for various parameters i.e. Thickness, Hardness, Weight variation, Friability, Disintegration time. All these formulations passed the criteria of IP. In case of formulations containing HPMC, viscosity was a major factor affecting the drug release. An inverse relationship existed between polymer viscosity and drug release; thus higher the polymer viscosity lower was the drug release. From stability studies (as per ICH guidelines) no significant change was observed in stability of optimized formulation batches. From the results it can be concluded that, the Matrix Tablet prepared using extracts of Rubia cordifolia is found to be a novel one.

Total Porosity 27.43 +0.03 37.03 +0.04 34.27 +0.02 37.03 0+.04 31.25 +0.03 30.23 +0.02

References:
1) 2) 3) 4) 5) 6) 7) Barar FSK. Essentials of Pharmacotherapeutics, S. Chand and Company Ltd, New Delhi, 2004 Page 117-119. Williamson EM. Dabour Ayurvedic Foundation, Major Herbs of Ayurveda, 1st edition, publisher, Churchill Livingstone, page 257-260. Quality standards of Indian medicinal plants. Vol-1 Indian Council of Medicinal Research, New Delhi 2003, page 208-211, 42-46. James Swarbrick and James C Boylan. Controlled and Modified-Release Drug- Delivery system, Encyclopedia of Pharmaceutical Technology. Vol-3, page 281 315. Leon Lachman, Herbert A Liberrman, Joseph L Kanig. The Theory and Practice of Industrial Pharmacy, 3rd edition, Varghese Publishing House, page 298-301, 302, 320, 325-329. Murina Momin, Amin AF and Pundarikakshudu K. Development and Evaluation of Triphala Formulations. Indian J. Pharm. Sci. 2004; 66(4): 427-432. ICH Q1A (R2), Stability Testing Guidelines: Stability Testing of New Drug Substances and Products, Page 1-22.

Table 6- Percent release profiles of formulations of Rubia cordifolia extract containing HPMC and ethyl cellulose % released of Drug Formulation code Time F1 F2 F3 F4 F5 F6 (hrs) 1 37.97 47.29 34.27 40.84 37.1 63.17 2 45.39 52.49 36.07 44.57 42.55 80.11 3 53.3 55.69 47.43 45.72 51.93 97.54 4 60.36 59.46 49.33 47.43 52.34 _ 5 63.17 61.7 53.09 49.12 53.93 _ 6 67.07 66.18 53.81 49.72 61.32 _ 7 70.99 68.66 54.39 62.42 66.66 _ 8 72.73 74.43 58.79 65.43 72.34 _ 9 80.11 78.5 59.9 70.13 82.86 _ 10 80.14 95.61 60.46 72.85 83.05 _ 11 83.79 97.36 61.11 73.01 86.25 _ 12 97.54 97.38 70.1 73.04 87.09 _

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