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Kelvin Bucktowar, et al., 2017/ Formulation and Evaluation of Fast Dissolving Tablets

International Research Journal of Pharmaceutical and Biosciences (IRJPBS) 4 (1) 44

RESEARCH ARTICLE

International Research Journal of Pharmaceutical and Biosciences

Pri -ISSN: 2394 - 5826 http://www.irjpbs.com e-ISSN: 2394 - 5834

Formulation and Evaluation of Fast Dissolving Tablets of Paracetamol using Ocimum basilicum Seed Mucilage as Superdisintegrant Kelvin Bucktowar1*, Sandeep Bucktowar2, Mili Bucktowar3, Luchmee Devi Bholoa4, Ganesh N.S5

1*,4 Department of Pharmaceutics, T. John College of Pharmacy, Gottigere, Bannerghatta Road, Bangalore-560083, Karnataka, India. 2Swinburne University of Technology, Melbourne, Victoria, Australia. 3Nanjing Medical University, Nanjing, Jiangsu Province, China. 5Professor and HOD of Pharmaceutics, T. John College of Pharmacy, Gottigere, Bannerghatta Road, Bangalore-560083, Karnataka, India.

Article info Abstract

Article history: Received 24 FEB 2017 Accepted 27 FEB 2017

*Corresponding author: [email protected]

Fast dissolving tablets (FDTs) are novel types of tablets that disintegrate or disperse in saliva within few seconds without water. The purpose of the present study was to develop a Fast dissolving tablet using Ocimum basilicum mucilage as a natural superdistintegrant obtained from pericarp of Ocimum basilicum seed (Sweet Basil Seed). Paracetamol was used as a model drug in this formulation. Paracetamol is a widely prescribed antipyretic and analgesic drug for all age groups. Several types of paracetamol products in the form of tablets, dispersible tablets, suspensions, syrups and FDTs are available commercially. Preformulation properties of tablet blend shows that the blend has good flow properties. Six formulations were prepared and post compression properties shows that the formulation F2 was the best formulation as it disintegrated within 18±0.01 seconds and drug release was 99.6% at 10minutes. It was subjected to accelerated stability studies at RH 75% and 400 C for a period of one month. The formulation was found to be stable.

KEYWORDS: Fast Disintegrating Tablet, Natural Superdisintegrant, Ocimum basilicum Seed Mucilage, Sweet Basil Seed, Paracetamol.

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INTRODUCTION Plant products serve as an alternative to synthetic products because of local accessibility, environment friendly nature and lower prices compared to imported synthetic products. India is one of the 12-mega biodiversity centers having about 10% of the world’s biodiversity wealth [1]. Many products from natural sources like plant exudates, gums, mucilage, and starches are utilized for preparation of pharmaceutical dosage forms like tablets, syrups, suspensions, emulsions, ointments and sustained drug release systems [2]. Sweet Basil Seeds are a boon and are considered to be a super food due to its tremendous qualities it possesses in terms of medicinal uses thanks to its different chemical constituents. Ocimum basilicum (Family: Lamiaceae) is also known as Sweet Basil. It has been used in traditional medicine due to its medicinal properties like antibacterial, antifungal, antispasmodic, carminative, diaphoretic, digestive, emmenagogue, expectorant, stimulant, stomachic [3]. Tablets are oral solid dosage forms which are conveniently self administrable, and are stable among various dosage forms. Hence, an accurate dose can be administered effectively. Fast dissolving tablets are designed to increase the bioavailability of the poorly soluble drugs[4]. Paracetamol is a NSAID used in various pain managements alone or in-combination with other anti-inflammatory drugs. It is available without a prescription since 1959 and it is known to be a common household drug [5]. The present work involves the formulation of Paracetamol fast disintegrating tablets using Ocimum basilicum mucilage obtained from the pericarp of the seeds of Ocimum basilicum(Family: Lamiaceae) as a superdisintegrant. MATERIAL AND METHODS MATERIALS Paracetamol (Acetaminophen), Superdisintegrant - Ocimum basilicum seed mucilage, Mannitol, Microcrystalline cellulose (PH102), Magnesium stearate, Talc, Peppermint flavor. All reagents are of analytical grade. METHODS [1,2,3,6,7] Isolation of Mucilage from Ocimum basilicum seeds: Sweet Basil seeds were rinsed with water to remove foreign particles. Seeds were soaked in water (seed: water= 1:10) for 20 minutes. The swollen seeds subjected to high agitation using homogenizer at 1500 rpm to separate gel layer from seeds. The separated gel layer was passed through muslin cloth to remove unwanted particles and then precipitated using acetone. The precipitate was washed with ethanol and dried in Hot air oven at 400C. The dried mucilage was powdered and stored in airtight containers. Organoleptic Evaluation: It was done to evaluate colour, odour, taste of the Isolated mucilage. Morphology: It was determined by X- ray diffraction, Scanning electron microscopy.



X- Ray diffraction: A Powder XRD (PXRD) pattern of mucilage was recorded using X-ray diffractometer (Figure 3). Scanning Electron Microscopy: The surface topography, morphology was determined by Scanning Electron Microscopy (Figure1 and Figure 2). Physicochemical Evaluation: These parameters are useful for the identification of purity of the compound. The Ocimum basilicum seed mucilage was evaluated for total ash, water soluble ash, acid insoluble ash and swelling index, alcohol soluble extractive, ether soluble extractive, loss on drying. Phytochemical Evaluation: 1% w/v solution of extract was prepared with distilled water. The extract was evaluated for carbohydrates, gums and mucilage. pH: pH of 1% w/v solution of Ocimum basilicum seed mucilage was determined using pH meter. PREFORMULATION STUDIES: Solubility studies: Solvents like distilled water, ethanol, 0.1N HCl, pH 7.2 phosphate buffer were used for the solubility determination of Paracetamol. Drug, Superdisintegrant Compatibility studies: FT-IR spectroscopy was used for compatibility study. Drug and Ocimum basilicum seed mucilage were mixed in 1:1 ratio and kept at 400C for 15 days. Drug and excipient mixture was taken and added with KBr (1:10) ratio and made a pellet. Spectrum of the drug, excipient mixture was scanned using FT-IR spectrophotometer in a range 4000-400cm-1. Determination of Bulk Density, Tapped density and compressibility index: All the materials were passed through sieve no. 60. Required quantity of each ingredient was taken for each specified formulation (Mentioned in Table 2) and all the ingredients were subjected to grinding to a required degree of fineness (except magnesium stearate). The powdered blend was evaluated for flow properties as follows:

• Angle of repose [8]

Angle of repose was determined using fixed funnel method. The blend was poured through a funnel that can be raised vertically until a maximum cone height (h) was obtained. Radius of the heap (r) was measured and the angle of repose (ө) was calculated using the formula. θ = tan -1 (h / r) • Bulk density [9] Bulk density was determined by pouring the blend into a graduated cylinder. The bulk volume (V) and weight of the powder (M) was determined. The bulk density was calculated by using the below mentioned formula,



Mass of granules(M) Bulk density = ---------------------------- Volume of granules(V)

• Tapped density [10] The measuring cylinder containing a known mass of blend was tapped for a fixed time. The minimum volume (Vt) occupied in the cylinder and the weight (M) of the blend was measured. The tapped density was calculated using the following formula, Weight of the blend Tapped density = ------------------------------------------ Volume occupied in the cylinder (Vt)

• Compressibility Index (Carr’s Index) [11] The compressibility index is determined by measuring both bulk density and the tapped density of a powder. Tapped density – Bulk density Compressibility Index (%) = -------------------------------------- × 100 Tapped density

• Hausner’s Ratio[12]

Hausner’s Ratio is determined by using the tapped density and the bulk density of the powder. Tapped density Compressibility Index (%) = -------------------- Bulk density EVALUATION OF THE FDTs:

• Weight variation [13] Twenty tablets were randomly selected from each formulation and average was determined. Then individual tablet was weighed and individual was compared with average weight.



• Friability [14] The friability of tablets was determined using friability test apparatus (Roche Friabilator) About 6 tablets (Initial Weight) were transferred into the Roche Friabilator. The apparatus was operated at 25 rpm for 4 minutes or 100 revolutions. The tablets were weighed again (Final Weight). The percentage friability was calculated by using following formula Initial Weight – Final Weight Friability = ------------------------------------- × 100 Initial Weight

• Hardness [4] The hardness of the tablets was determined using Pfizer hardness tester. Ten tablets were randomly selected from each formulation and hardness of the same was determined .The results are expressed in average value.

• Thickness [4] Twenty tablets were randomly selected from formulations and thickness was measured individually by using a Vernier caliper. It was expressed in millimeter and average was calculated.

• In vitro disintegration time [15] In the disintegration time study, the tablets were taken and introduced in each tube of disintegration apparatus, and the tablet rack of the disintegration apparatus was positioned into a 1-litre beaker containing 900ml of distilled water and time of disintegration was recorded at 37 ± 2°C.

• Wetting time [16] Five circular tissue papers of 10cm diameter are placed in a Petri dish with a 10cm diameter. Ten millimeters of water-containing Eosin, a water-soluble dye, is added to Petri dish. A tablet is carefully placed on the surface of the tissue paper. The time required for water to reach upper surface of the tablet is noted as a wetting time.

• Water Absorption Ratio: A piece of tissue paper folded twice was placed in a small Petri dish containing 6 ml of water. A tablet was put on the tissue paper and allowed to completely wet. The wetted tablet was then weighed. Water absorption ratio(R) was determined using following equation. Wa – Wb Water absorption ratio(R) = -------------- × 100 Wa Where, Wa = Weight of tablet after water absorption Wb = Weight of tablet before water absorption.



• Dissolution Rate Study [17]

In-vitro dissolution rate study was done by using USP Type I apparatus which was rotated at 150 rpm. Phosphate buffer pH 7.2 (900 ml) was taken as dissolution medium. Temperature of the dissolution medium was maintained at 37±0.5°C. Aliquots of dissolution medium were withdrawn at specific time interval and it was filtered. Absorbance of filtered solution was determined by Spectrophotometer at 249 nm and drug concentration was determined from standard calibration curve. The dissolution rate studies for all designed formulations were done as presented in table 5.

• Stability studies [18] Stability of a drug has been defined as the ability of a particular formulation, in a specific container, to remain within its physical, chemical, therapeutic and toxicological specifications. The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity and light and enables recommended storage conditions, re test periods and shelf life to be established. In the present study, the FDTs are packed in suitable packaging and stored under the following conditions for a period as prescribed by ICH guidelines for accelerated studies 40±20C, RH 75%±5%. The tablets were withdrawn after period of one month and analyzed for physical characterization (visual defects, hardness, friability, disintegration, dissolution etc) and drug content. RESULTS AND DISCUSSION Pre Compression studies The prepared tablets were evaluated for their flow properties, the results for the blends of compression tablets were shown in Table 3. The bulk density and the tapped density for all formulations were found to be almost similar. The Carr’s index and Hausner’s ratio were found to be in the range of ≤ 20 % and 1.13 to 1.24 respectively, indicating good flow and compressibility of the blends. The angle of repose for all the formulations was found to be 28.120 to 32.220 indicating very good flow. Post Compression Studies for Formulation of Fast Dissolving Tablets of Paracetamol The Post Compression Studies for Formulation of Fast Dissolving Tablets of Paracetamol was illustrated in Table 4. The weight variations of tablets were within the range of ±7.5% complying with pharmacopoeia specifications of IP. The thickness of tablets was found to be 3.80 mm. The hardness for different formulations was found to be between 3.70 ±0.18 to 3.99 ±0.18 Kg/cm2, indicating satisfactory mechanical strength. The friability was < 1.0% w/w for all the formulations, which is an indication of good mechanical resistance of the tablet. The drug content was found to be within limits from 99.1±0.02 to 99.8±0.01%. The Invitro disintegration time (s) was found to be between 18±0.01 to 196±0.03. The wetting time was between 16-60 seconds. Water Absorption Ratio was found to be from 90 to 153. In-vitro dissolution studies of Paracetamol tablets in phosphate buffer 7.2: The absorbance of the solution was measured at 249nm using UV spectrometer with Phosphate buffer pH 7.2 as blank. The values are shown in Table No 5. A dissolution graph was plotted by taking



absorbance on Y-axis and concentration (µg/ml) on X-axis as shown on Table No 6. The percentage drug release was found to be from 80.2 to 99.6. Characterization of Ocimum basilicum seed mucilage Table 1: Characterisation of Ocimum basilicum seed mucilage.

Serial Number Test Observation 1 Colour Brownish yellow 2 Odour Characteristic 3 Physicochemical Evaluation Total Ash 3.465%w/w Water Soluble Ash 1.4%w/w Acid Insoluble Ash 0.2%w/w Ethanol Soluble Extractive 4%w/w Ether soluble extractive 4.2%w/w Loss on drying 2% Swelling Index 1712.5 4 Phytochemical Evaluation Test for carbohydrates

Molisch Test: To the test solution add few drops of alcoholic α- naphthol, and then add few drops of concentrated sulphuric acid through sides of test tube.

Purple to violet color ring appeared at the junction

Gums and Mucilages a) Treat the test solution with Ruthenium red solution. b) The extract is treated with 25ml of absolute alcohol, and filtered.

Pink colour was observed Swelling of extract was observed

Flow properties Angle of repose 190.42” Bulk density 0.732g/CC Tapped density 0.732g/CC Compressibility Index 12.75% Hausner’s ratio 1.14 6 pH 7.8



Table 2: Formulation of Fast disintegrating tablets of Paracetamol using Ocimum basilicum seed Mucilage as superdisintegrant.

Ingredients F1 F2 F3 F4 F5 F6 Acetaminophen 325 325 325 325 325 325 Microcrystalline cellulose

77.5 77.5 77.5 77.5 77.5 77.5

Superdisintegrant-Ocimum basilicum seed mucilage

32.5 65.0 97.5 130 162.5 195.0

Talc 5 5 5 5 5 5 Magnesium Stearate 5 5 5 5 5 5 Peppermint Flavour 1 1 1 1 1 1 Mannitol 204 171.5 139.0 106.5 74.0 41.5 Total Weight 650 650 650 650 650 650

Table 3: Pre-formulation parameters.

Parameters F1 F2 F3 F4 F5 F6 Angle of repose(Ө) 32.220 30.010 29.530 28.120 28.230 29.350 Bulk density(g/cm3) 0.38 0.42 0.39 0.38 0.39 0.40 Tapped density(g/cm3) 0.47 0.50 0.46 0.43 0.44 0.45 Carr’s Index(%) 19.1 16.0 15.2 11.6 11.3 11.1 Hausner’s Ratio 1.24 1.19 1.18 1.13 1.13 1.13

Table 4: Post formulation parameters.

Ingredients F1 F2 F3 F4 F5 F6 Hardness Test (Kg/cm2)

3.99 ±0.18 3.92 ±0.24 3.70±0.18 3.86±0.20 3.75 ±0.18 3.88 ±0.18

Thickness (mm) 3.8 3.8 3.8 3.8 3.8 3.8 Friability (%) 0.85 0.88 0.79 0.82 0.76 0.77 Invitro disintegration time (s)

30.00±0.02 18±0.01 35±0.03 58±0.03 120±0.04 196±0.03

Wetting time (s) 21 16 30 42 55 60 Water Absorption Ratio

90 96 102 120 131 153



Table 5: Percentage Drug Release.

Percentage Drug Release

Time(mins) F1 F2 F3 F4 F5 F6

0 0 0 0 0 0 0 1 84.2 90.1 82.3 75.4 35.9 22.2

2 87.3 92.2 84.3 77.4 72.5 30.9

3 89.8 95.0 86.8 78.1 76.0 55.5

4 92.4 97.1 87.7 78.7 77.1 75.1

5 95.6 98.5 89.9 80.3 77.8 78.3

10 99.0 99.6 94.6 87.1 83.0 80.2

Table 6: Percentage Drug Release Graph.



Figure 1: SEM of Ocimum basilicum seed mucilage.

Fig 2: SEM surface view of Ocimum basilicum seed mucilage.

SEM photographs shows that the mucilage powder is irregular in shape and has porous nature.



Fig 3: XRD of Ocimum basilicum seed mucilage

CONCLUSION Mucilage from Ocimum basilicum was successfully extracted and characterised. Pre formulation studies revealed that there is no incompatibility between drug and excipients. Six batches of Paracetamol fast disintegrating tablets using different percentages of Ocimum basilicum seed mucilage were prepared and evaluated for pre compression and post compression parameters. Among them, formulation F2 was the best formulation as it disintegrated within 18±0.01 seconds and drug release was 99.6% at 10 minutes. In this study, it was found that on increasing the concentration of Ocimum basilicum seed mucilage above 65.0mg there is decrease in disintegration due to the formation of viscous plug around the surface of the tablet. REFERENCES 1. Kadam P V, Yadav KN, Jagdale SK, Shivatare RS, Sumeet K, Patil MJ. Evaluation of Ocimum sanctum

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