The drug delivery technology has certainly infused new interest incitingly, traditional of old drugs by providing them new life specially through their therapeutic targets1.Recent developments in the technology have presented viable dosage alternatives from oral route for paediatrics, geriatrics, bedridden, nauseous or non-compliance patients2. A fast dissolving drug delivery system in most cases, is a tablet that dissolves or disintegrants in the oral cavity without the need of water or chewing3-4.
The basic approach used in development of fast dissolving tablet by the use of synthetic superdisintegrants like Croscarmellose, sodium starch glycolate, poly vinyl pyrrolidone, etc.5-8 Number of natural, semi synthetic and synthetic polymer material are used in the various drug delivery system. Recent trend towards the use of vegwetable and non- toxic products demands the replacement of synthetic additives with natural one9. Aceclofenac is a potent inhibitor of the enzyme cyclo-oxygenase, which is involved in the production of prostaglandins. Aceclofenac can be administered twice daily as 100mg orally in the treatment of rheumatoid arthritis. Geriatric patients may have difficulty in swallowing and chewing the tablets resulting in patient non compliance and ineffective theraphy10-12. Objective of my study to formulate and evaluate Aceclofenac fast dissolving tablets by direct compression method and to increase the drug release profile in short duration of time. Evaluation of formulated tablets was done using various quality parameters like hardness, friability, wetting time, DT, in vitro dissolution study.
An annual plant, namely Trigonellum foenum – graecum, (Fam:-Fabaceae) which is commonly called as Fenugreek. in tamil – vendhayam. The plant has small round leaves, cultivated in worldwide as semi-acrid crop13. It has been used since ancient times both as food and medicine by the people living on the shores of Mediterranean and across Asia.The seeds are brownish yellow and have peculiar odor14.
MATERIALS AND METHODS
Aceclofenac, Sodium Starch Glucollate, cross carmellose sodium, cross povidone, Microcrystalline cellulose was obtained as gift nsamples from Microlabs, Hosur. Fenugreek seeds was purchased in the local market. Magnesium stearate was obtained as gift sample from central drug House pvt.Ltd. Talc, Dextrose was purchased from Spectrum reagents and chemicals pvt, Ltd.
Method of Preparation
Fast dissolving tablets containing 300mg of Aceclofenac were prepared by direct compression method, each tablet containing 100mg of Aceclofenac was prepared by using direct compression as per formula given in the superdisintegrants SSG, MCC, Cross povidone, Cross Carmellose Sodium (5%, 10%, 15%) and Fenugreek (5%, 10%, 15%) were used in different combination. All the ingredients were passed through sieve #60 and kept in hot air oven at 60⁰ C to make anhydrous and accurately weighed. The drug, superdisintegrants, MCC, dextrose, were mixed to improve drug distribution and content uniformity and triturated well in a mortor. Then magnesium stearate, and talc was passed through sieve #80 mixed and blended well with initial mixture. The mixed blend of drug and excipients was compressed using single punching machine to produce tablet weighing 300mg having diameter 4.5mm, following the procedure six batches of MDT of Aceclofenac sodium in different ratio of superdisintegrants were prepared.
Evaluation of Powder Blends
Bulk density (ρb) to a measure used to describe a packing of particles. It is (gm/ml) and was determine using a balance and measuring cylinder. Initially the weight of the measuring cylinder was taken. Then, 4 gm pre sieved (40#) bulk drug were poured into the measuring cylinder using a funnel and weighed (M). Then volume of the powder (Vb) was taken. Bulk density of the granules was calculated using following formula.
Bulk density = Weight of powder/ Volume of powder
ρb = M / Vb
Tapped Density16, 17
The granular powder mixture was tapped for a fixed (500) number of taps. The minimum volume (Vt) occupied in the cylinder and the weight (M) of the blend was measured. The tapped density (Electro Lab ETD 1020) (ρt) was calculated using following formula.
Bulk density = Weight of powder/ Volume of powder
ρb = M/ Vt
Carr’s Index (Ci)18
Tapped and bulk density measurements can be used to estimate the carr’s index of a material. Carr’s index was determined by,
Carr’ index = ((Tapped density – bulk density) / Tapped density) %
Angle of Repose
Angle of repose (α) was determined by funnel method. The blend was poured through a funnel that can be raised vertically until a maximum cone height (h) was obtained. The radius of the heap (r) was measured and angle of repose was calculated. It is used to determine the flow property of powder
α = tan ‐1 (h/r)
Hausner’s ratio is a guide of ease of powder flow; it is calculated by following formula.
Hausner ratio = Tapped density/ Bulk density
Hausner ratio = ρt/ ρb
Evaluation of Fast Dissolving Tablets
Quality Control tests for FDTs of all formulations were performed, and the average values were calculated. All the tablets were evaluated for different parameters as appearance, weight variation, hardness, thickness, friability, wetting time, water absorption ratio, disintegration time, and In vitro dissolution study
Tablets from each formulation were randomly selected and organoleptic properties such as colour, odour, taste, and shape were evaluated.
Twenty tablets were selected randomly from each batch weighed individually on electronic balance (Shimadzu). The individual weighed is then compared with average weight for the weight variations.
For each formulation, the hardness of tablets was determined using the Monsanto hardness tester.
A piece of tissue paper (10.75×12 mm) folded twice was placed in a culture dish (d=6.5cm) containing 6ml of water. A tablet was put on the paper and the time for complete wetting was measured.
Water Absorption Ratio20
The test was done with the same procedure as that of wetting time.in this test initial weight of the tablet was taken before placing on petridish. After complete wetting the wetted tablet was taken and then weighed. Water absorption ratio, R was determined using the equation
R=100(Wb-Wa) / Wa
Where Wa is the weight of tablet before water absorption
Wb is the weight of tablet after absorption
It was determined by USP tablet disintegration test apparatus (electrolab USP ED-2AL) using 900 ml of distilled water without disk at room temperature. Test was performed on 6 tablets. Limit for the disintegration time of FDTs: Not more than 30 seconds according to USP.
In Vitro Drug Release21, 22
In vitro drug release of aceclofenac from fast dissolving tablets was determined using USP Dissolution Apparatus II (Paddle type) (Electrolab TDT- 08l U.S.P). The dissolution test was performed using 900 ml of phosphate buffer (pH 7.4) at 37 ± 0.5 0 C. The speed of rotation of paddle was set at 50 rpm. At a predetermined time interval (5 min); 5 ml samples were withdrawn, filtered through whatman filter paper. Absorption of solution was checked by UV spectrophotometer at 276 nm and drug release was determined from standard curve.
Determination of Drug Content23, 24
Amount of drug present in each tablet was determined by taking 20 tablets, and then it was crushed in a mortar. Then the powder equivalent to 100mg of drug was transferred to 100ml standard flask. The powder was dissolved in 5ml of methanol and made upto volume with phosphate buffer pH 6.8. The sample was mixed thoroughly and filtered the solution was diluted suitably and analyzed for drug content by UV spectrophotometer at 274nm using phosphate buffer pH 6.8 as blank.
Table 1: Different Types of Formulation F1-F6
|2.||Fenugreek seeds powder||10||20||30||–||–||–|
|3.||Soduim Starch Glycollate||–||–||–||10||20||30|
|5.||Cross Carmellose Sodium||–||–||–||–||–||–|
Table 2: Different Types of Formulation F7-F12
|2.||Fenugreek seed powder||–||–||–||–||–||–|
|3.||Soduim Starch Glycollate||–||–||–||–||–||–|
|5.||Cross Carmellose Sodium||–||–||–||10||20||30|
RESULTS AND DISCUSSION
Fast Dissolving tablets were designed to disintegrate rapidly on contact with saliva and enables oral administration without water or chewing, these formulations offer increased convenience and ease of administration. The tablets were prepared by Direct Compression method by using natural and synthetic superdisintegrants such as Fenugreek seed powder, Sodium starch glycollate, Cross povidone, Cross carmellose sodium etc to optimize the disintegration, in-vitro dissolution, drug content.
The preformulation studies are the first step in the development of any formulation. The goal of this study is to establish physical characteristics. The absorption maxima shows the λ max at 285nm.
The weight variation for the Aceclofenac fast dissolving tablets passes the I.P limit.
The hardness of the tablet shows 3-4kg/cm found to be optimum and also the tablets were showed around then only.
Table 3: Derived Properties of Formulations F1-F6
|1.||Angle Of Repose||28040’ ± 0.769||26060’ ± 0.317||28050’±0.057||28090’± 0.692||24094’±0.577||26011’±0.080|
|2.||Bulk Density||0.56 ± 0.0065||0.57 ± 0.040||0.58 ± 0.004||0.62 ± 0.007||0.64 ± 0.008||0.65 ± 0.008|
|3.||Tapped Density||0.64 ± 0.008||0.64 ± 0.008||0.65 ± 0.008||0.73 ± 0.001||0.75 ± 0.0.017||0.76 ± 0.0.017|
|4.||Carr’s Index||11.56 ± 0.152||11.23 ± 0.635||11.30 ± 0.70||15.03 ± 0.251||15.06 ± 0.850||14.05 ± 0.360|
|5.||Hausners Ratio||0.88 ± 0.001||0.89 ± 0.006||0.89 ± 0.007||0.84 ± 0.002||0.84 ± 0.008||0.85 ± 0.009|
The friability test showed for all the formulations i.e from F1-F12 should not more than 1%.
Disintegration time for tablets prepared with Fenugreek was greater to that prepared with sodium starch glycollate, cross povidone, cross carmellose sodium indicating that Fenugreek had good disintegrating property. This rapid disintegration of the fast dissolving tablets was due to the penetration of saliva into the pores of the tablet which lead to the swelling of superdisintegrants to create enough hydrodynamic pressure for quick and complete disintegration of the tablet. Fenugreek was effective at concentration i.e 30%.
Fenugreek was effective at concentration at 30%. In –vitro dissolution study reveals that F3 was an optimized formulation that releases more than 90% of drug within 5minutes as compared with other formulations.
Table 4: Derived Properties of Formulations F7-F12
|1.||Angle Of Repose||27027’ ± 0.300||26004’± 0.753||27038’± 0.344||27038’± 0.835||28003’± 0.837||28030’± 0.663|
|2.||Bulk Density||0.58 ± 0.007||0.59 ± 0.003||0.60 ± 0.004||0.58 ± 0.007||0.57 ± 0.006||0.57 ± 0.010|
|3.||Tapped Density||0.64 ± 0.0127||0.64 ± 0.0080||0.65 ± 0.0085||0.64 ± 0.0126||65.00 ± 0.0215||0.63 ± 0.0080|
|4.||Carr’s Index||10.01 ± 0.781||09.06 ± 0.665||08.08 ± 0.529||09.73 ± 0.757||11.06 ± 0.776||08.53 ± 0.585|
|0.89 ± 0.007||0.90 ± 0.006||0.91 ± 0.007||0.90 ± 0.007||0.88 ± 0.035||0.91 ± 0.005|
Table 5: Evaluation of Various Parameters from F1-F6
|1||Hardness||3.41 ± 0.0601||3.54 ± 0.3234||3.79 ± 0.2516||3.55 ± 0.0763||3.58 ± 0.0907||3.57 ± 0.1331|
|2||Friability||0.48 ± 0.0288||0.45 ± 0.050||0.33 ± 0.0288||0.23 ± 0.0288||0.25 ± 0.05||0.28 ± 0.0288|
|3||Weight Variation||0.302 ± 0.002||0.305 ± 0.004||0.313 ± 0.011||0.306 ± 0.002||0.304 ± 0.001||0.303 ± 0.001|
|4||Disintegration Time||0.59 ± 0.01||0.42 ± 0.023||0.33 ± 0.032||0.79 ± 0.017||0.75 ± 0.011||0.67 ± 0.005|
|5.||Wetting Time (s)||45||43||40||90||80||70|
|6.||Water Absorption Ratio(%)||81 ± 0.23||85 ± 0.71||89 ± 0.81||60 ± 0.42||70 ± 0.41||75 ± 0.31|
Table 6: Evaluation of Various Parameters from F7-F12
|1.||Hardness (kg/cm3)||3.30 ± 0.076||3.69 ± 0.236||3.84 ± 0.153||3.81±0.136||3.66±0.176||3.76±0.332|
|2.||Friability (%)||0.36 ± 0.057||0.43 ± 0.057||0.43 ± 0.057||0.46±0.057||0.35±0.050||0.33±0.057|
|3.||Weight Variation||0.3017 ± 0.0002||0.3045± 0.0045||0.3043 ± 0.0036||0.3028±0.0157||0.3083±0.082||0.3033±0.016|
|4.||Disintegration Time (minutes)||0.89 ± 0.01||0.82 ± 0.020||0.63 ± 0.015||0.72±0.026||0.65±0.023||0.48±0.015|
|6.||Water absorption ratio(%)||65 ± 0.32||69 ± 0.51||77 ± 0.25||80±0.36||76±0.85||67±0.68|
Table 7: In-Vitro Dissolution Study of F1-F6
Table 8: In-Vitro Dissolution Study of F7-F12
|S. No||Time (min.)||F7||F8||F9||F10||F11||F12|
Our study showed a significant and enthusiastic report by achieving a Aceclofenac formulations which is rendering a fast dissolving aptitude as tablets by direct compression method by enhancing an excellent bioavailability. Apart from that the formulations of aceclofenac showed better drug releasing tendency which was
obtained only by the natural superdisintegrants, Fenugreek than other synthetic formulations. This may owing to the penetration of saliva fluid into the pores of the accessed tablet which increases the swelling ability of superdisintegrants to create enough hydrodynamic pressure for quick and complete disintegration. Finally from our reports it was confirmed that the natural superdisintegrants have amicable caliber in fast dissolving nature of Aceclofenac and still the future work on this natural superdisintegrants is under process.
The author is thankful to our guide for her guidance, valuable support and providing necessary facilities to carry out the research work.
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Last Udpated: 19-10-2018