Evaluation of binding property of mucilage from Litsea glutinosa wall

Background: Litsea glitinosa is an evergreen tree of medium size which grows to a height of about 20 to 30 feet. It belongs to family Lauraceae. In India it is found mainly in North Eastern region. The leaves and the mucilage from the bark of plant is utilized in the gum for poultices. Methods: Mucilage of Litsea glutinosa was isolated from powdered bark by continuous hot extraction technique using water and precipitation by absolute alcohol (38% w/w yield). The mucilage was evaluated for binding properties in tablets and granules, using paracetamol as a model drug. The granules were prepared using 4 different concentrations of mucilage (4%, 6%, 8%, and 10%) and evaluated for percentage of fines, average particle size, total porosity, compressibility index, and flow properties. The prepared tablets were evaluated for content uniformity, hardness, friability, disintegration time, and in vitro dissolution profiles. Results: The results obtained with the lower concentrations of mucilage, that is, less than 6% were not so encouraging. The tablets prepared by using 10% mucilage of L. glutinosa as binder exhibited more hardness as compared with the starch. Conclusion: It may be concluded that the concentration ranging from 6% to 8% of L. glutinosa mucilage may be considered as better option as a binding agent for the preparation of tablets as compared to the starch (10%).


INTRODUCTION
Litsea glutinosa is an evergreen tree of medium size, which grows to a height of about 20-30 ft. It belongs to the family Lauraceae. L. glutinosa is found in mixed primary and secondary forest and thickets. Distributed from India through Indo-China toward the Malesian area where it grows in all parts, and northern Australia. In India it is found mainly in North Eastern region. The seeds contain an aromatic oil, which has been used to make candles and soap. The roots yield fibers used in Thailand for rope manufacture and for paper pulp. The fruits have a sweet creamy edible pulp that can be taken as food. The young leaves are used as fodders. The powdered seeds are also applied medicinally against boils. The leaves and the mucilage in the gum from the bark have been used for poultices. The bark also acts as a demulcent and mild astringent in diarrhea and dysentery. [1] The essential oil of the plant is reported to have psychopharmacologic actions. [2] Kar et al also reported that the essential oils of L. glutinosa have beneficial effects on the isolated tissue of the cardiovascular system. [3] The methanolic extract of the bark have antibacterial activity against 16 different microorganisms as reported by Mandal et al. [4] The bark of the plant L. glutinosa also contains alkaloids that have been identified and reported by Yang et al. [5] Mucilages of L. glutinosa is a hetero-polysaccharide, polyuronides consisting of sugar and uronic acid units. [6] They are usually formed from the cell wall or deposited on it in layers. They swell in water and form a gel. [6] The usefulness of mucilages as emulsifying, gelling, and suspending agents has been well documented. [7] Some of the mucilages have also been used in tablet formulations as binding agents and also to sustain the drug release. [8] The present investigation is carried out to study the binding property of the mucilage obtained from L. glutinosa in tablet manufacturing.

Plant material
The bark of L. glutinosa was collected from Guwahati. The Background: litsea glitinosa is an evergreen tree of medium size which grows to a height of about 20 to 30 feet. It belongs to family Lauraceae. In India it is found mainly in North Eastern region. The leaves and the mucilage from the bark of plant is utilized in the gum for poultices. Methods: Mucilage of Litsea glutinosa was isolated from powdered bark by continuous hot extraction technique using water and precipitation by absolute alcohol (38% w/w yield). The mucilage was evaluated for binding properties in tablets and granules, using paracetamol as a model drug. the granules were prepared using 4 different concentrations of mucilage (4%, 6%, 8%, and 10%) and evaluated for percentage of fines, average particle size, total porosity, compressibility index, and flow properties. The prepared tablets were evaluated for content uniformity, hardness, friability, disintegration time, and in vitro dissolution profiles. Results: the results obtained with the lower concentrations of mucilage, that is, less than 6% were not so encouraging. the tablets prepared by using 10% mucilage of L. glutinosa as binder exhibited more hardness as compared with the starch. Conclusion: It may be concluded that the concentration ranging from 6% to 8% of L. glutinosa mucilage may be considered as better option as a binding agent for the preparation of tablets as compared to the starch (10%).

Key words:
barks were cut into small pieces and dried in a hot air oven at 60°C. The chips were powdered in a mechanical grinder. Paracetamol was used as a model drug in the study. All the chemicals and other reagents used in the study were of AR grade.

Isolation of mucilage
The weighed quantity (30 g) of bark powder was extracted with solvent ether in a soxhalate apparatus for about 6-8 h. The marc was dried and macerated overnight with absolute alcohol. The supernatant liquid was discarded after maceration. Again the defatted and decolorized powder was macerated for about 18-20 h with 5% aqueous acetic acid solution. Maceration process was repeated three times for complete extraction of mucilage. The extract was filtered and concentrated to about 50 mL by evaporation on a water bath. Lastly, the mucilage was precipitated completely by the addition of an excess of absolute alcohol. The mixture was filtered and washed repeatedly with absolute alcohol. The filtrate was dried till constant weight at 100°C and the percentage of mucilage with reference to air-dried bark was calculated. The percentage of mucilage found was 38% w/w. The mucilage was powdered and passed through sieve number 80. The powdered mucilage was stored in a desiccator until further use. [9] Physicochemical and microbial properties of mucilage The physicochemical properties, such as solubility, swelling index, loss on drying, viscosity, and microbial load of the mucilage, were determined according to the Indian pharmacopoeial procedures. [10] The pH of the mucilage was determined using a digital pH meter.

Preparation and evaluation of granules
Paracetamol was used as a model drug to formulate granules. Starch was used as disintegrant, whereas lactose and talc were used as diluent and lubricant, respectively, as per the guidelines of standard text. The binder solution was prepared by dissolving the mucilage of L. glutinosa in water at 4%, 6%, 8%, and 10% w/v concentrations. The granules of batch size 150 g were prepared by wet granulation method. [11,12] The drug, lactose, talc, and starch were mixed thoroughly, and a sufficient volume of ~30 mL of 4%, 6%, 8%, and 10% w/v of mucilage of L. glutinosa was added slowly to the powder blend, and kneading was performed for ~10 min until formation of a dough mass with enough cohesiveness. The dough mass was forced through a sieve no. 16 (1180 µm) and dried at 50°C in a hot air oven for 12 h. The dried granules were re-sieved through a sieve no. 20 (850 µm). The prepared granules were then evaluated for percentage of fines, particle size, and flow properties (by measurement of angle of repose). [13,14] The bulk and tapped densities of the granules were assessed in accordance with the USP 25 using a tapped volumeter apparatus. Compressibility index of the granules was determined by Carr's compressibility index. [13][14][15] Total porosity was determined as described by measuring the volume occupied by selected weight of a powder and the true volume of granules. [13][14][15]

Preparation and evaluation of tablets
The tablets were compressed by using single punch machine with concave-faced punches. A batch size of 100 tablets was prepared. The prepared tablets were evaluated for content uniformity, hardness, friability, disintegration time, and in vitro dissolution profile by Indian Pharmacopoeia 1996 method. [16]

RESULTS AND DISCUSSION
The dried and coarsely powdered tubers of L. glutinosa yielded a high percentage (38% w/w) of mucilage using absolute alcohol as mucilage-precipitating solvent. The physicochemical properties of mucilage were determined and shown in Table 1. The extracted and purified mucilage was evaluated for pH, which was found to be 7.2.
The prepared granules were evaluated for percentage of fines, particle size, and flow properties [ Table 2]. It was observed that the percentage of fines was reduced as the concentration of mucilage was increased. The percentage of fines was a little higher in granules prepared using 6% w/v mucilage of L. glutinosa as binder but 8% concentration may be considered good as compared with the starch of 10% w/v. The flow property of granules was determined by angle of repose, which was found to be 30° to 32°. The mean particle size (between 0.31 and 0.38 mm) was found to be satisfactory for preparation of tablets. Hence all the granules exhibited good flow properties [ Table 2]. The bulk densities of the prepared granules were found to decrease significantly by increasing the concentrations of L. glutinosa mucilage and was found to be lowest (0.498 ± 0.037) at 10% w/v. This result may be due to the formation of larger agglomerates and the decrease in fines in the granules, because increasing the concentrations of mucilage provides more binding to the granules. The compressibility index [ Table 2] indicates a decrease in flowability with increasing L. Glutinosa mucilage. In general, compressibility index values up to 15% result in good to excellent flow properties. [17] Percentage porosity values of the granules ranged from 30.29% to 38.32%, indicating that the granules are loosely packed and confirming that the particles are not of variable sizes. In general, a percentage porosity value below 26% shows that the particles in the powders are of variable sizes, and a value greater than 48% shows that the particles in the powder are in the form of aggregates or flocculates. [18] All the results indicate that the granules prepared using different concentrations (4%, 6%, 8%, and 10%) possess satisfactory flow properties, compressibility, and porosity.
Four batches of 100 tablets were prepared with mucilage of L. glutinosa of different concentrations (4%, 6%, 8%, and 10%) and evaluated for content uniformity, hardness friability, disintegration time, and in vitro dissolution profiles, and so on [ Table 3].
The tablets exhibited good content uniformity. The hardness of tablets increased with increase in the percentage of binding agent. The tablets prepared with 10% mucilage of L. glutinosa were showing more hardness compared with tablets prepared with 10% starch mucilage. The percentage friability values were constant in all the batches of tablets prepared by using different concentrations of mucilage. Disintegration time of 10% w/v concentration of L. glutinosa mucilage was higher in comparison with the tablets prepared by using 10% w/v of starch mucilage.
The dissolution profile (in vitro) indicates that the 8% w/v concentration of L. glutinosa mucilage is more uniform and almost more than 80% of the drug gets released within 3 h, but in the 10% concentration, drug release is slightly less [ Figure 1]. The trend of drug release was found decreasing with increase in concentration of L. glutinosa mucilage. The result showed that the drug release from the tablets prepared using mucilage of 4%, 6%, and 8% w/v concentrations of L. glutinosa mucilage was more than 85% in 180 min [ Figure 1].
It has been observed from the study that the bark of the plant L. glutinosa has high mucilage content (38% w/w of dried bark), so the plant may be taken as a good natural   source of mucilage. The results also show that the mucilage of L. glutinosa has better binding property as compared with starch and it is also economical compared with starch. Furthermore, L. glutinosa mucilage can also be evaluated for sustained drug release from tablets, since the tablets prepared using mucilage of L. glutinosa produced a sticky film of hydration on the surface, which may reduce the drug release rate. Hence L. glutinosa mucilage can be evaluated for its efficacy in the formulation of sustained release tablets.