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Water soluble mucilage was isolated from the fruits of Cordia dichotoma ( Boraginaceae family). The physical Characteristics of the gum such as solubility, swelling index, loss on drying, PH, viscosity and microbiological properties were studied. The gum was found take non-toxic when evaluated for acute toxicity in mile (LD50>5 gm/kg body weight P.O). The mucilage was evaluated for their granulating and binding properties in tablets, using Nimesulide as model drug. The mucilage were used at 4 different concentrations viz. 4,6,8 and 10% w/w. Wet granulation techniques was used for preparation of granules. The prepared granules were evaluated for % fines, average particle size, Bulk density and Angle of repose. These properties were compared with starch, which was used as a standard binder at 10% concentration. The tablets were punched by using a cadmach single punch machine and were evaluated for weight variation, Hardness, friability and Disintegration time. The Caesalpinia pulcherrima mucilage was found to possess excellent binding property and could be used as a binder in conventional tablet formulation.
KEY WORDS: Cordia dichotoma, mucilage, Binder, tablets.
Binders are agents used to impart cohesive qualities to the powdered material during the production of tablets. They impart cohesiveness to the tablet formulation, which ensures that the tablet remains intact after compression as well as improving the free flowing quality. Mucilages are most commonly used adjuvant in pharmaceutical preparations. They possess a variety of pharmaceutical properties, which include binding, disintegrating, suspending, emulsifying and sustaining properties. Natural mucilage are preferred over semi-synthetic and synthetic materials due to their non-toxic, low cost, free availability, emollient and non-irritating nature. The present study deals with the isolation of the gum from the seeds at Caesalpinia pulcherrima and its application as binding agent in tablet formulation. The binding properties of this gum were compared with starch which was used as a standard binder at 10% concentration.
MATERIALS AND METHODS
The plant fruits of Cordia dichotoma were collected from surrounding area of Anantapur, Andhra Pradesh, India. The collected plant was authenticated by department of Botany, Sri krishnadevaraya University, Andhra Prasesh, India. Nimesulide was obtained as a gift sample from Walkman and Selman labs, Antapur, Andhra Prasesh, India. Micro crystalline cellulose was obtained from Sd Fine chemicals, Mumbai, India. All other materials used in the study were of analytical grade.
ISOLATION OF MUCILAGE
3.1 Extraction of mucilage:
Fresh Cordia dichotoma fruits were procured. The seeds do not contain any mucilage and were removed prior to extraction. The fruits were sliced, homogenized with five times its weight of water, centrifuged at 4000 rpm for 15 min and the clear, viscous solution decanted. The mucilage was precipitated with three volumes of ethanol and washed with more ethanol followed by acetone. The mucilage so obtained was dried under vacuum (less than 1 Torr at 25°C for 12 h).
3.2Purification of the Mucilage
General methods of isolation of gums from food were used. The crude mucilage (1 %) was homogenized (Potter homogenizer) with cold dilute tri chloro acetic acid solution (5%). The solution was centrifuged (3500 rpm for 20 min), neutralized with sodium hydroxide by drop wise addition and then dialyzed for 30 h against distilled water. The mucilage was precipitated with ethanol (in the quantities of three times the volumes) and washed successively with ethanol, acetone and diethyl ether.
PHYSICOCHEMICAL PROPERTIES OF GUM
The physicochemical properties, such as solubility, swilling index, loss on drying, viscosity, pH and microbial load8 (No. of CFU/gm of gum) were determined according to Indian Pharmacopoeial procedure7, Using air dried powder of gum. The pH of the mucilage was determined using a digital pH digital meter. The viscosity of 1% gum solution was determined at 25oC using ostwalds viscometer after 24 hr of hydration.
Drug-Excipient compatibility studies
Differential Scanning Calorimetry (DSC)
DSC analysis was performed using Shimadzu DSC-60, Shimadzu Limited Japan. A 1:1 ratio of drug and excipient was weighed into aluminum crucible. The sample was analyzed by heating at a scanning rate of 200C over a temperature range 200-3000 under nitrogen environment.
Fourier Transform Infrared (FTIR) Spectroscopy
FTIR spectra were recorded on samples prepared in potassium bromide (KBr) disks using a Shimadzu Corporation, (Tokyo, Japan) Model-1601 PC. Samples were prepared in KBr disks by means of a hydrostatic press at 6-8 tons pressure. The scanning range was 500 to 4000 cm-1.
PREPARATION AND EVALUATION OF GRANULES
All the materials were passed through a mesh sieve with aperture of 250μm before use. The tablets were prepared by wet granulation method. The compositions of tablets were given in table 1. Diclofenac sodium and lactose were thoroughly mixed and the solution of the mucilage of specified concentration was prepared by dispersing the mucilage in water. The mucilage solutions were used for moistening the powder mixture, for preparing tablets to evaluate the binding potential. The wet mass was then passed through sieve no. 16 and dried at temperature not exceeding 500C in a hot air oven for 30minute. The dried granules were rescreened through a sieve no 20. The same method was followed in the preparation of standard formulation (ST I) using starch mucilage 10% w/w concentration as a binder. The granules were evaluated for their particle size, the particle size were estimated by sieving method, sieves were arranged in a nest with coarsest at the top a sample of 15g of the granules were placed on the top sieve. The sieve set were fixed and shaken for a sudden period of time (20minutes) the granule retained on the each sieves were weighed. Frequently, the granules were assigned the mesh number of the screen through which it passed or on which it was retained. It was expressed in terms of arithmetic mean of the two sieves
The powdered blend was evaluated for flow properties viz., Angle of repose, loose bulk density (LBD), tapped bulk density (TBD), Carr's compressibility index, and hausner's ratio
Table 1: Flow properties of dried Cordia dichotoma fruit mucilage
Angle of repose (0)
Loose Bulk Density (g/ml)
Tapped Bulk Density (g/ml)
Compressibility index (%)
Number of experiments (n)= 3
Table 2: Formulae of matrix tablets
Cordia dichotoma fruit mucilage
Micro crystalline cellulose (Avicel)
Total weight of tablet
PREPARATION OF TABLETS
The granules were lubricated with 2% w/w magnesium stearate and talc. The tablets were
compressed by using Cadmach single punch machine using 6mm round flat faced punches. The tablets of average weights 220mg were prepared. 9 batches of tablets were prepared by using isolated mucilages of five different concentration (2%, 4%, 6% 8% and 10%) were used, starch mucilage (10% concentration) was used as a standard binder for comparison.
Post compression parameters:
The thickness of the tablets was determined using a thickness screw gauge (Mitutoyo, New Delhi, India). Five tablets from each batch were used and average values were calculated.
Hardness indicates the ability of a tablet to withstand mechanical shocks while handling. The hardness of the tablets was determined using Monsanto hardness tester. It is expressed in kg/cm2. Three tablets were randomly picked and analyzed for hardness. The mean and standard deviation values were also calculated.
The friability of tablets was determined using Roche Friabilator. The friabilator was operated at 25 rpm for 4 minutes or run up to 100 revolutions. The % friability was then calculated by eq.1.
F= Winitial - Wfinal / Winitial X 100 ……………. (1)
F= friability (%), Winitial = initial weight, Wfinal = Final weight
Weight variation test
To study weight variation, 20 tablets of each formulation were weighed using an electronic balance (Denver APX-100, Arvada, Colorado) and the test was performed according to the official method.
Drug content uniformity
Tablet containing 8mg of drug is dissolved in 100ml of 0.1N HCl taken in volumetric flask. The drug is allowed to dissolve in the solvent. The solution was filtered, 1ml of filtrate was taken in 50ml of volumetric flask and diluted up to mark with 0.1N HCl and analysed spectrophotometrically at 284 nm. The concentration of Domperidone in mg/ml was obtained by using standard calibration curve of the drug. Claimed drug content was 10mg per tablet. Drug content studies were carried out in triplicate for each formulation batch.
In-vitro disintegration time
The process of breakdown of a tablet into smaller particles is called as disintegration. The in-vitro disintegration time of a tablet was determined using disintegration test apparatus as per I.P. specifications. Place one tablet in each of the 6 tubes of the basket. Add a disc to each tube and run the apparatus using pH 6.8 (simulated saliva fluid) maintained at 37±20C as the immersion liquid. The assembly should be raised and lowered between 30 cycles per minute in the pH 6.8 maintained at 37±20C. The time in seconds taken for complete disintegration of the tablet with no palpable mass remaining in the apparatus was measured and recorded.
In-vitro dissolution studies
In vitro release studies were carried out using tablet dissolution test apparatus USP XXIII. The following procedure was employed throughout the study to determine the in-vitro dissolution rate for all the formulations. The parameters in-vitro dissolution studies were tabulated in table 5.
Accelerated Stability studies:
The promising formulations (F4 and F5) were tested stability for a period of 3 months at accelerated conditions of a temperature 400C and a relative humidity of 75% RH, for their drug content12.
RESULTS AND DISCUSSION:
Infrared Spectrum of Nimesulide Pure drug, Infrared Spectrum of Cordia dichotoma fruit mucilage, Infrared Spectrum of Nimesulide with Cordia dichotoma fruit mucilage, shows the formation of matrix material without any negative interactions which were represented in Fig. 1, 2 and 3 respectively.
The Cordia dichotoma fruit mucilage was yellow in colour, soluble in water and forms hage viscous solution. The % yield was 23 ±2.173 g /kg with average particle size of 165.15±10.265µm and the weight loss on drying was found to be 4.20±2.573. The Swelling ratio was found to be 45±3.841, pH was found to be 7.0±0.56 and the Charring was found to be 220±4.520 C. The density of 0.5% w/v liquid was found to be 0.997±0.055 and microbial count of bacteria was 5cfu/g and Fungi were 2 cfu/g. The Angle of repose of Cordia dichotoma fruit mucilage were found to be 27.96±1.6840, Loose Bulk density was found to be 0.604±0.018 g/cm3, Tapped bulk density was found to be 0.866±0.021 g/cm3, Compressibility Index was found to be 0.302±0.023%, Hausner's ratio was found to be 1.434±0.047. All the above were conducted in 5 trials. The thickness of formulated tablets was uniform and ranged from 5.8±0.41 to 6.2±0.15, the hardness of formulated tablets were more than 5 kg/cm2 indicating good mechanical strength and the loss on friability was less than 1% which indicates the formulated tablets can withstand the physical stress while transportation.
In-vitro drug release profile of Nimesulide from formulated matrix tablets were studied using zero order, first order, Higuchi, Korsmeyer Peppa's and Hixson-Crowell's Models which were shown in Fig. 5, 6, 7, 8 and 9 respectively. The rate of release was faster in F-1 and slower in F-5. The kinetic plots were perfectly fitting to the formulated Cordia dichotoma fruit mucilage- Nimesulide matrix tablets. This result shown that as the proportion of Cordia dichotoma fruit mucilage increased, the overall time of release of the drug from the matrix tablet was also increased. Drug releases from matrix tablets were by drug dissolution, drug diffusion or a combination of both.
The present study revealed that Cordia dichotoma fruit mucilage appears to be suitable for use as a release retardant in the manufacture of prolonged release matrix tablets because of its good swelling, good flow and suitability for matrix formulations. From the dissolution study, it was concluded that dried Cordia dichotoma fruit mucilage can be used as an excipient for making prolonged release matrix tablets.
The authors are thankful to Walkman and Selman Pharmaceuticals, Anantapur, India for providing the pure drug sample.
Table 1: Physicochemical characterization of Cordia dichotoma fruit mucilage
Slowly soluble in water
produces hage viscous solution
% yield (g /kg)
Ave. particle size
Weight loss on drying
Density of liquid (0.5% w/v)
Microbial count (cfu/g)
Bacteria:6 ; Fungi: 3
Angle of repose (q°)
Loose Bulk density (g/cm3)
Tapped bulk density(g/cm3)
Number of trials (n)=5
Figure No. 10: Infra Red Spectrum of Nimesulide
Figure No. 15: Infra Red Spectrum of Formulation