INTRODUCTION:

Glucosamine is a naturally occurring substance composed of sugar and amine used for the treatment of Osteo-arthritis, Rheumatoid-arthritis and Inflammation ^1,2. GS believed to produce the cartilage cells as Glucosamine glycons and proteoglycans which are the building blocks of the cartilage tissue. GS has a short biological half-life and the usual oral dose is 2.5gm in three divided dose after meals. To reduce the frequency of administration and to improve the patient compliance sustained release formulation of Glucosamine is desirable.

The most commonly used method of modulating the drug release is to include it in a matrix system ³. It composed of polymers and other exepients as vehicle for drug delivery are extremely popular in controlling the release rate in which drug that is dissolved or dispersed. Matrix tablets are having excellent advantage like reduced frequency of administration, increased patient compliance and also involve least processing variables, utilizing the conventional facilities and accommodate large dose of drug⁴.

Hence, in the present work, an attempt has been made to develop sustained release matrix tablet of G.S using hydrophilic materials such as Luctaman (xanthone gum) and Xanulac (guar gum) ⁵. The objective of the study were to investigate the performance of hydrophilic matrix system and to reduce the dose frequency there by improve the patient compliance.

MATERIALS:

Glucosamine sulphate 2KCl was procured from Pharma Medicare, Bangalore. Luctaman (xanthone gum) and Xanulac (guar gum) were purchased from Lcid colloids Ltd, Mumbai, India. Microcrystalline cellulose (MCC) and magnesium stearate were obtained from Merck, Ltd, Mumbai, India. All the other ingredients used were of high analytical grade.

METHODS:

Preparation of SR Matrix tablet:

Glucosamine SR matrix tablet were prepared by wet granulation technique ⁶. Drug and different concentration of Polymers (10, 15, 20, 25 and 30%) at 1:1 ratio and Mcc were accurately weighed, sieved through 40 mesh and mixed in a poly bag. Sufficient value of granulating agent (water and methylene chloride) was added. After enough cohesiveness was obtained, the mass was sieved through 12 mesh and dried at 60^oc for 1hr. The dried granules were blended with magnesium stearate and talc as lubricant and glident. The blend was compressed using 19.5X9.1mm punch in 16 stations, single rotary compression machine.

Table: 01 Evaluation of tablet

S.N.	Formulation (Batch No.)	Bulk Density (g/cm³)	Tapped Density (g/cm³)	CI (%)	Angle of Repose (θ)	Hard ness (Kg/ cm²)	Avg. Thick ness (mm)	Friability (%)	Drug Content
1	001	0.445	0.549	17.12	36.31	5.5	5.56	0.1097	100.78
2	002	0.640	0.745	14.09	40.13	6.5	5.60	0.1922	100.46
3	003	0.635	0.725	12.41	33.30	6.0	5.56	0.0540	100.78
4	004	0.562	0.690	18.55	37.9	6.5	5.58	0.6441	103.11
5	005	0.600	0.731	17.80	38.65	7.0	5.60	0.1959	99.04
6	01	0.586	0.719	18.52	40.13	5.0	5.56	0.0724	97.58
7	02	0.630	0.745	15.43	37.95	5.0	5.54	0.2159	103.78
8	03	0.572	0.695	17.65	33.30	5.5	5.54	0.1070	103.80
9	04	0.632	0.740	14.59	39.8	6.0	5.58	0.0267	103.98
10	05	0.493	0.599	17.69	37.9	6.5	5.60	0.173	101.41
11	1	0.532	0.648	18.05	33.82	5.5	5.58	0.1741	100.39
12	2	0.568	0.678	16.22	33.32	5.5	5.56	0.0989	98.78
13	3	0.630	0.745	15.43	33.82	6.0	5.58	0.4397	100.38
14	4	0.492	0.595	17.32	38.65	6.5	5.54	0.2481	100.75
15	5	0.658	0.772	14.76	36.31	6.5	5.58	0.6570	98.47

EVALUATION OF GRANULES:

Angle of repose:

The Angle of repose was measured according to the Funnel method. This indicates the flow ability of granules. The Angle of repose calculated by using the following equation ⁷.

tan= h/r

Where h and r are the height and radius of the powder.

Bulk density:

Loose Bulk density (LBD) and tapped Bulk density (TBD) were calculated by following formulas ⁸,

Compressibility index:

The Compressibility index of the granules was determined by Carr’s Compressibility index ⁹.

EVALUATION TABLET:

Thickness:

The thickness of the tablet was determined using a thickness gauge (Mitutoya, Japan). Five tablets of each tablet were used and average values were calculated.

Weight Variation test:

To study the weight variation, 20 tablet of each formulation were weighed using an electronic balance (ES -10 Balance) and the test was performed according to the official method ¹⁰.

Hardness and Friability:

For each formulation, the hardness and friability of six tablets were determined using the Monsanto hardness tester (Cadmach, Ahamedabad, India) and Rouche friabilator (Electro lab, Mumbai, India) respectively.

Drug Content:

Five tablets were weighed individually and the drug extracted with water. The absorbance was measured at 240nm by using UV-visible spectrophotometer ¹¹. (Shimadzu, Japan)

Invitro release studies:

The invitro dissolution studies were carried out using USP apparatus type-ll (Electro lab, India) at 100rpm ¹². The dissolution medium consisted of 0.1N hydrochloric acid for the first 2hrs and the phosphate buffer pH 7.4 from 3 to 12hrs (900ml), maintained at 37^oC± 0.5^oC. The drug release at different time intervals was measured at 240nm by using UV- Visible spectrophotometer.

Aging Studies:

Stability studies carried out at 25^oC /60^o C RH and 40^oC/75^oC RH for the best formulation up to 8 weeks according to the ICH guidelines.

RESULTS AND DISCUSSION:

The SR matrix tablet of GS was conceptualized based on the fact that, in clinical practice GS is used as an anti-inflammatory agent in the treatment of Osteo-arthritis and GS is usually supplemented for its reported cartilage rebuilding ability. The mechanism of action of GS and its pharmacokinetics after oral administration is not clearly understood. Hence, the sustained release form of GS was expected to be more beneficial. Because GS is mucopolysaccharides with higher molecular weight, there is difficulty in transportation of drug across the gastrointestinal mucosa; therefore it was thought that if drug were released slowly, the absorption would be better. The granules were evaluated for Angle of repose, Bulk density, and Carr’s index. The Bulk density, Angle of repose and Carr’s index for all the formulation were lies between the range of 0.445 - 0.772, 33^o- 40^o and 2.41 ± 0.09%- 18.55 ± 0.05% respectively. The values of Bulk density indicated good packing characteristic, Angle of repose indicated good flow property and Carr’s index indicated free flowing ability.

All the formulations were subjected to thickness, weight variation, hardness, friability and drug content. The results of all the formulations complied with official pharmacopoeia. The hardness was found to be 5.50-7.0 Kg/cm². The loss in total weight in friability was less than 1%, indicates that matrix tablet are compact and hard. The drug content was found to be 95-105% of the labelled amount. The results were reproducible, even tablets (Batch IV) that had been stored about 6months at 25^oC and 60% RH.

FIG. 1 Dissolution Profile Of Glucosamine Matrix Tablet Using Luctaman

FIG.2 Dissolution Profile of Glucosamine Matrix Tablet Using Xanulac

The dissolution profile revealed that the drug release was found to influence by the polymer concentration employed in the formulation. The content of polymer present as a low concentration shows the drug release within a shorter time.

While increasing polymer concentration the release of drug from the formulation take place prolonged period of time. Batch 004 showed the required release when compared to the marketed product. The best concentration of the polymer is 25% at 1:1 ratio of Luctaman (xanthone gum) and Xanulac (guar gum), which sustained the drug release up to 12hrs. This may be due to synergistic effect exhibited by Xanthone gum with guar gum in the ratio of 1:1.

To know the drug mechanism of drug release, the dissolution data was employed by zero order, first order, and Higuhi and Peppas equation. The correlation co-efficient values revealed that the dissolution profile followed zero order kinetics and the mechanism of drug release was predominantly controlled by non-fickian diffusion.

FIG.3Dissolution Profile of Glucosamine Matrix Tablet Using Luctaman and Xanulac Combination (1:1)

In conclusion the release rate of the drug from matrix tablet governed by the concentration of polymer. Thus the required release of GS attributed by using 25% concentration of Luctaman and Xanulac at 1:1 ratio. This system provides a significant and convenient method for achieving sustained release in oral dosage forms.

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Received on 24.12.2008 Modified on 29.01.2009

Research J. Pharm. and Tech.2 (3): July-Sept. 2009,;Page 463-465