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ejbps, 2015, Volume 2, Issue 6, 08-19.

SJIF Impact Factor 2.062

2349-8870 European Journal Biomedical Europeanof Journal of Biomedical and Pharmaceutical ISSN sciences Volume: 2 Issue: 6 AND Pharmaceutical sciences

Faruki et al.

08-19 Year: 2015

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UNEXPECTED DIFFERENCES IN DISSOLUTION BEHAVIOR OF TABLETS PREPARED FROM FENOFIBRATE SOLID DISPERSIONS AND STRONGLY ENHANCED DISSOLUTION RATE, EXCLUSIVELY BETTER THAN MARKETED PRODUCTS Md. Zakaria Faruki1,2*, Mohiuddin Ahmed Bhuiyan1, Md. Fakrul Alam3, Rishikesh1, Rehana Akhter1, A K M Mofasser Hossain4 1

Department of Pharmacy, University of Asia Pacific, Dhanmondi, Dhaka-1209, Bangladesh. Quality Assurance Department, Healthcare Pharmaceuticals Ltd., Dhaka-1205, Bangladesh. 3 Production Department, Healthcare Pharmaceuticals Ltd., Dhaka-1205, Bangladesh. 4 Department of Wine, Food and Molecular Biosciences, Lincoln University, New Zealand.

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*Author for Correspondence: Md. Zakaria Faruki Senior Officer, QA,Quality Assurance Department, Healthcare Pharmaceuticals Ltd., Dhaka-1205, Bangladesh.

Article Received on 25/08/2015

Article Revised on 16/09/2015

Article Accepted on 07/10/2015

ABSTRACT Fenofibrate is used to reduce cholesterol levels in patients at risk of cardiovascular disease. As it is poorly water soluble drug, solid dispersions were prepared by different methods in our previous studies and were then formulated into 600 mg tablet equivalent to 40 mg of Fenofibrate. Different polymers like poloxamer 188, PVP, poloxamer 407, HPMC 6cps, PEG 6000 and mannitol were used to prepare the solid dispersions. Characterization of pre-compression (angle of repose, bulk density, tapped density, compressibility index, hausner ratio) and compression (thickness, hardness, weight variation, friability, drug content and disintegration tests) properties of the granules, powder and tablets were evaluated. In this study, it was shown that the incorporation of super disintegrant, sodium starch glycolate (SSG), in solid dispersion tablets containing a high drug load can strongly enhance the dissolution rate of the highly lipophilic drug fenofibrate. In addition, the dissolution rate was increased when SSG was incorporated in the tablet containing solid dispersions than when it was physically mixed with the solid dispersions. Solid dispersion tablets based on poloxamer 188 (99.37%), PVP (92.68%), poloxamer 407 (92.58%) showed a much faster dissolution than those based on HPMC 6 cps (85.23%), PEG 6000 (79.20%) and mannitol (72.32%). But Tablet which prepared only physical mixing with excipients without any technique released only 26.31%. The differences in dissolution behavior of tablets prepared from solid dispersions were very much unexpected. The dissolution rate enhancement strongly depended on super disintegrants and type of hydrophilic polymers used in the formulations. Maximum formulations displayed highest fitting with Higuchi release pattern and some formulations also displayed with Korsmeyer release model for solid dispersion. Lowest number fitted with zero order kinetic model of drug release. The dissolution profiles of formulated tablets were compared with the marketed products which showed exclusively better release profile than marketed products. KEYWORDS: Fenofibrate, solid dispersion technique, dissolution, tablet, marketed products.

INTRODUCTION The poor solubility and low dissolution rate of poorly water soluble drugs in the aqueous gastro-intestinal fluids often cause insufficient bioavailability rather than the limited permeation through the epithelia[1] and the formulation of poorly soluble drugs for oral delivery now presents one of the major challenges to formulation scientists in the industries.[2] Poorly water-soluble drugs often require high doses in order to reach therapeutic plasma concentrations after oral administration. Improvement in the extent and rate of dissolution is highly desirable for such compounds, as this can lead to

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an increased and more re-producible oral bioavailability and subsequently to clinically relevant dose reduction and more reliable therapy. Now-a-days, pharmaceutical technology provides many approaches to enhance the dissolution rate of poorly soluble drugs. Physical modifications often aim to increase the surface area, solubility and/or wettability of the powder particles and are therefore focused on particle size reduction or generation of amorphous states.[3,4] Fenofibrate is a drug of the fibrate class. It is mainly used to reduce cholesterol levels in patients at risk of

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European Journal of Biomedical and Pharmaceutical sciences

cardiovascular disease. Like other fibrates, it reduces both low-density lipoprotein (LDL), very low density lipoprotein (VLDL) and triglycerides levels whereas increases high-density lipoprotein (HDL) level. It also appears to have a beneficial effect on the insulin resistance featured by the metabolic syndrome. It is used alone or in conjunction with statins in the treatment of hypercholesterolemia and hypertriglyceridemia. So it has been used for many years to lower cholesterol levels and its pharmacokinetic profile is well understood.[5.6] It is practically insoluble in water[7,8] and has high lipophilicity[2] (logP=5.24). Thus the dissolution rate of fenofibrate is expected to limit its absorption from the gastrointestinal tract. Combinatorial chemistry and High Throughput Screening are modern techniques in drug research. Many of the drugs can be categorized as class II drugs according to the Biopharmaceutics Classification System[9]. These drugs are poorly water soluble, but once they are dissolved they are easily absorbed over the gastro-intestinal membrane.[10,11] Therefore, the bioavailability after oral administration can be improved by enhancement of the dissolution rate.[12] One of the approaches to enhance the dissolution rate is the use of fully amorphous solid dispersions.[13,14] Solid dispersion is a system composed of a hydrophilic matrix in which a poorly soluble drug is dispersed. The enhanced dissolution rate of drugs from these solid dispersions is mainly based on four different mechanisms[15,16 ,17]: (1) wetting of the drug is improved by direct contact of the drug with the hydrophilic matrix, (2) the saturation concentration around small particles is higher than around large particles[18], (3) the surface area is increased and (4) the drug has higher energy in the amorphous state than in the crystalline state, through which the saturation concentration is increased.[19,20,21] Poor water solubility is the major drawback for the various types of drugs and many approaches have been introduced for the solubility enhancement of such drugs. Solid dispersion is one of the techniques adopted for the formulation of such drugs and various methods are used for the preparation of solid dispersion like kneading method, solvent evaporation method, supercritical method, fusion method. Recently various types of carriers like surfactants, disintegrants have been included in the solid dispersion formulations, named as third generation solid dispersion.[22] Polymers incorporated in solid dispersion technologies are usually hydrophilic in nature and also showing compatibility with the drug to enhance the drug solubility. The study also encompasses the criteria of solvent selection, challenges in formulation of solid dispersion dosage forms, future prospects and various types of marketed preparations.[23] To increase the dissolution rate from these solid dispersions, the uncontrolled crystallization in the near vicinity of the dissolving tablet should be prevented.[24] Incorporation of a surfactant in the tablet could be an

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option to achieve this result. So the present experiment was designed to check the effect of preparing tablet with the solid dispersions of fenofibrate on the release profile of the drug. MATERIALS AND METHODS Drugs and chemicals: Fenofibrate (Nexchem Pharmaceutical Co. Ltd., China) was a gift from The White Horse Pharmaceuticals Ltd., Dhaka, poloxamer 188, poloxamer 407, mannitol, lactose, starch, avicel pH 102, purified talc and sodium starch glycollate were procured from BASF, Germany. PEG 6000 and PVP were purchased from Loba Chemicals, India. HPMC 6cps (Samsung, Korea), magnesium stearate (Cabot Sanmar Limited, India), methanol (Merck, Germany), ethanol (Merck, Germany), powdered sodium lauryl sulphate (Merck, Germany) and sodium starch glycolate (SSG) were procured from local vendors and purified water from own research laboratory of the Department of Pharmacy, University of Asia Pacific. Instruments and Equipments: UV-VIS spectrophotometer (UV-1601, Shimadzu, Japan), tablet dissolution tester USP XIII (TDT-06T, Electrolab, India), electronic balance (AY120, Shimadzu, Japan), water bath (Shimadzu, Japan), sonicator (Power Sonic 505, Hwashin Technology Co., Korea), pH Meter (pH 211 Microprocessor, Hanna Instruments, Germany), vortex mixer (VM-2000, Dig system laboratory Instrument Inc, Taiwan), hair dryer (Miyako Super 1200W, China), oven (Precision Scientific Co. Bangladesh), KBr press-single punch tablet compression machine (M-15, Techno Search Instruments, Technological Essentials, India). Characterization of Powders and Granules Fenofibrate tablets were prepared with direct compression process. Prior to compression, granules and powders were evaluated for their characteristic parameters. Angle of repose[25] was measured by fixed funnel method. Bulk density and tapped density were determined by cylinder method, and Carr’s Index (CI) and Hausner ratio were calculated. Preparation of Fenofibrate Immediate Release Tablet by Direct Compression All the ingredients were accurate weighed and taken in a mortar and blended well with pestle for about 5 minutes. Then lubricants (talc & magnesium stearate) were added and mixed by vortex mixer. Appropriate amounts of the mixture were accurately weighed and taken in a PerkinElmer hydraulic press equipped with 13 mm diameter flat faced punch and die set (punch & die were previously lubricated with a 1% dispersion of magnesium stearate in ethanol) for compression using normal hand pressure (NMT 4 tons). A round shaped immediate release core tablets of fenofibrate were then prepared.

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Table 1: Formulations of 600 mg tablet for the equivalent weight of fenofibrate 40 mg from pure fenofibrate & solid dispersions for all carriers in different ratios (1:1, 1:3, 1:5, 1:7 and 1:10) with qs excipients

Sl. No.

Compositions

Fenofibrate 40 1. mg or equivalent to 40 mg 2. Lactose 3. Starch 4. Avicel pH 102 5. Talc Magnesium 6. stearate Sodium starch 7. glycolate Total weight per tablet

Fenofibrate Tablet

Tablet of solid dispersion (mg) Different ratio of drug & carriers 1:3(F2) 1:5(F3) 1:7(F4)

1:1(F1)

40

80

160

240

320

440

460 10 45 10

420 10 45 10

340 10 45 10

260 10 45 10

180 10 45 10

60 10 45 10

5

5

5

5

5

5

30

30

30

30

30

30

600 mg

600 mg

600 mg

600 mg

600 mg

600 mg

Characterization of Formulated Fenofibrate Tablets Single punch compression machine with 13 mm diameter punch and die was used to compress fenofibrate mixture as stated earlier. The properties of the compressed tablet, such as hardness, friability were determined. A slide calipers was used to measure the diameter and thickness of the tablet discs. Hardness of 5 tablets from each formulation was tested using Veego hardness tester. The hardness of tablets was measured in kg. Twenty tablets were randomly selected from each batch individually weighed, the average weight and standard deviation of 20 tablets was calculated. Friability means the ability to reduce a solid substance into smaller pieces with little effort. The integrity of the tablet formulation was assessed by rotating 10 tablets from each formulation in a tablet friability tester. Tablet friability tester equipped with a specific rotating disk. Weight of 10 tablets was taken. The tablets were introduced into the rotating disk and it was allowed to rotate at 25 rpm for 4 minutes. At the end of the rotation, tablets were collected and weigh of the tablets were taken. Disintegration time was calculated taking 6 tablets from each formulation. It was found within the range of 5 to 12 minutes.

In vitro dissolution study of Formulated Fenofibrate Tablet In vitro dissolution study of fenofibrate tablet was performed in a dissolution test apparatus (Electrolab, India) type II (Paddle) at rotation speed of 75 rpm was used for the study. Dissolution of every tablet was carried out on an equivalent of 40 mg of the fenofibrate in 900 ml 0.75% sodium lauryl sulfate in distilled water as dissolution media and the temperature was set at 37±0.5oC. At different intervals (5, 10, 15, 20, 30, 45 and 60 min) samples of 5 ml were withdrawn and the samples were replaced with fresh dissolution medium. Then the sample was filtered and diluted for 2 times and then assayed by UV spectrophotometer (Shimadzu 1601, Shimadzu Corporation, Japan) at 291 nm. It was made clear that none of the ingredients used in the formulations interfered with the assay. To increase the reliability of the observations, the dissolution studies were performed in triplicate. RESULT AND DISCUSSION Physical Parameters of Powder Average angle of repose, bulk density, tapped density, CI, Hausner ratio etc. of powder formulations prepared for the compression of fenofibrate tablets are summarized in Table 2.

Table 2: Results of pre-compression properties Average Angle of Bulk Density Formulations Repose (θ) (in (gm/cm3) * Degree) * FP188-I (F1) 22.88 0.576 FP188-III (F2) 22.60 0.561 FP188-V (F3) 21.03 0.558 FP188-VII (F4) 20.40 0.553 FP188-X (F5) 22.68 0.569 FP407-I (F1) 22.00 0.574 FP407-III (F2) 23.45 0.572 FP407-V (F3) 22.28 0.538 FP407-VII (F4) 20.46 0.559

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1:10(F5)

Tapped Density (gm/cm3) * 0.721 0.718 0.731 0.732 0.741 0.724 0.730 0.682 0.712

Compressibility Index (%) * 21.866 20.111 18.463 18.025 16.13 23.212 21.644 21.489 20.830

Average Hausner Ratio* 1.212 1.220 1.231 1.234 1.302 1.231 1.246 1.270 1.294

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FP407-X (F5) 21.75 FPEG-I (F1) 20.62 FPEG-III (F2) 21.46 FPEG-V (F3) 21.45 FPEG-VII (F4) 23.24 FPEG-X (F5) 24.38 FPVP-I (F1) 23.42 FPVP-III (F2) 24.12 FPVP-V (F3) 25.06 FPVP-VII (F4) 25.65 FPVP-X (F5) 26.89 FHPMC-I (F1) 24.44 FHPMC-III (F2) 22.46 FHPMC-V (F3) 21.84 FHPMC-VII (F4) 21.13 FHPMC-X (F5) 20.42 FMAN-I (F1) 20.08 FMAN-III (F2) 20.18 FMAN-V (F3) 24.12 FMAN-VII (F4) 22.62 FMAN-X (F5) 23.55 *All values are expressed as mean ± SD, n=3


0.574 0.568 0.539 0.558 0.542 0.526 0.547 0.534 0.576 0.551 0.547 0.573 0.560 0.529 0.526 0.572 0.556 0.573 0.580 0.551 0.562

0.725 0.708 0.716 0.730 0.705 0.722 0.716 0.728 0.731 0.687 0.720 0.723 0.671 0.726 0.691 0.732 0.708 0.735 0.696 0.708 0.713

19.718 24.635 24.124 23.562 23.121 22.142 26.648 25.671 23.666 21.845 21.624 24.713 23.761 23.327 21.458 24.015 25.823 24.704 20.175 24.243 16.052

1.304 1.246 1.278 1.308 1.301 1.321 1.250 1.363 1.263 1.308 1.352 1.262 1.310 1.324 1.259 1.224 1.264 1.256 1.304 1.309 1.316

Physical Parameters of Formulated Fenofibrate Tablets The average diameter and thickness were found as 13.00 ±0.1 mm and 3.2 ± 0.05 mm for all formulations. Hardness of all the formulated tablets ranged from 6.2 Kg to 10.50 Kg (Figure 1A). The average weight was found within the range of 600±5 mg. So the uniformity of weight was found within acceptable range as according to compendial requirement tablets having weight more than 250 mg should not more 5% for uncoated tablet. The average % friability was found less than 0.8%, which was well within the acceptable range of 1% and indicates the tablet surfaces are strong enough to withstand mechanical shock or attrition during storage and transportation until they are consumed. The disintegration time was also well within the acceptable range of 15 minutes for uncoated tablets (Figure 1B).

A)

B)

Figure 1: Comparison of A) average hardness and B) in-vitro disintegration time for various formulations of fenofibrate tablet

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Table 3: Results of post compression properties of fenofibrate tablets Formulations

Hardness (Kg) *

Thickness (mm) *

Diameter (mm) *

FP188-I (F1) 6.25 3.20 13.00 FP188-III (F2) 6.58 3.22 13.01 FP188-V (F3) 7.52 3.20 13.00 FP188-VII (F4) 8.05 3.20 13.00 FP188-X (F5) 8.32 3.21 13.01 FP407-I (F1) 7.44 3.20 12.99 FP407-III (F2) 7.56 3.20 13.00 FP407-V (F3) 8.18 3.20 13.00 FP407-VII (F4) 8.36 3.22 13.00 FP407-X (F5) 9.32 3.21 13.00 FPEG-I (F1) 7.41 3.20 13.00 FPEG-III (F2) 7.68 3.20 13.01 FPEG-V (F3) 9.15 3.20 13.00 FPEG-VII (F4) 9.58 3.23 13.00 FPEG-X (F5) 10.48 3.21 12.99 FPVP-I (F1) 8.04 3.20 12.99 FPVP-III (F2) 8.26 3.20 13.00 FPVP-V (F3) 8.83 3.20 13.00 FPVP-VII (F4) 9.68 3.19 13.00 FPVP-X (F5) 10.50 3.24 12.99 FHPMC-I (F1) 6.20 3.20 13.01 FHPMC-III (F2) 7.05 3.20 13.00 FHPMC-V (F3) 7.21 3.20 13.00 FHPMC-VII (F4) 6.36 3.22 13.01 FHPMC-X (F5) 7.34 3.21 13.01 FMAN-I (F1) 8.26 3.20 13.00 FMAN-III (F2) 7.56 3.20 13.00 FMAN-V (F3) 8.35 3.21 13.00 FMAN-VII (F4) 7.75 3.18 13.00 FMAN-X (F5) 8.88 3.20 13.01 *All values are expressed as mean, n=5; **All values are expressed mean, n=6; *** All values are expressed as mean, n=10 In Vitro Dissolution Study of Various Formulated Tablets This study was intended to observe release pattern of drug from the solid dispersion tablets from various formulations by using different carriers which generally change the nature of the insoluble drug to amorphous form and on the other hand super disintegrating agent which helps to enhance the rate of drug release. The complete comparative study of 600 mg various tablets for the equivalent weight of fenofibrate 40 mg various tablets formulated by pure crystal fenofibrate with excipients and solid dispersion (SD) with excipients. The rate of dissolution was excellently increased that tablets which were formulated from SDs. Comparatively tablet prepared from SD showed more drug release then the release of SDs. This is due to technological effect of SD, super disintegrating agents and excipients. Moreover formulations showed their highest release for the tablets formed by SD 1:10 (drug:carrier). Average release

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Weight Avg. % Avg. DT variation Friability (min) (mg) ** *** 600 ±0.03 0.19 10.00 600±0.02 0.18 9.35 601±0.01 0.19 7.46 602±0.02 0.20 6.48 599±0.02 0.16 6.05 600±0.01 0.23 10.51 602±0.02 0.18 11.15 603±0.01 0.21 10.12 598±0.01 0.20 9.50 599±0.03 0.23 8.26 602±0.03 0.19 11.00 601±0.02 0.32 10.22 599±0.02 0.38 10.45 602±0.02 0.27 11.55 600±0.01 0.22 12.00 599±0.01 0.42 11.08 597±0.01 0.35 10.45 598±0.02 0.29 11.42 598±0.01 0.21 11.58 599±0.01 0.18 12.00 596±0.04 0.66 8.52 597±0.03 0.71 8.40 598±0.02 0.52 7.55 595±0.05 0.66 5.28 596±0.05 0.58 5.00 598±0.03 0.44 6.39 600±0.02 0.47 8.42 599±0.01 0.42 9.08 603±0.02 0.38 9.42 602±0.02 0.45 8.30 as mean ± SE, n=20. DT values are expressed as

profile of six tablets from each formulation is shown as a comparative release profile of fenofibrate tablet and tablet from SD. In this study, it was shown that the incorporation of super disintegrants (e.g., SSG) in solid dispersion tablets containing a high drug load can strongly enhance the dissolution rate of the highly lipophilic drug fenofibrate. In addition, the dissolution rate was more increased when the super disintegrant, (SSG) was incorporated in the drug containing solid dispersions than when it was physically mixed with the solid dispersions[26]. The dissolution rate enhancement strongly depended on the type of super disintegrant. The dissolution behavior also depended on the type of hydrophilic carriers. Solid dispersion tablets based on poloxamer 188, PVP, poloxamer 407 showed a much faster dissolution than those based on HPMC 6 cps, PEG 6000 and mannitol (Figure 2).

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Figure 2: Zero order release kinetics of various tablet formulation from fenofibrate and (series-1: poloxamer 188 based solid dispersion, series-2: poloxamer 407 based solid dispersion, series-3: PEG 6000 based solid dispersion, series-4: PVP based solid dispersion, series-5: HPMC based solid dispersion, series-6: mannitol based solid dispersion) The percent drug release of various tablet formulation from fenofibrate and SDs of different carriers were ranging from 52.44% to 99.37% in 60 min. The lowest was for FPEG-I (F1) and the highest release was for FP188-X (F5). Poloxamer 188 based solid dispersion tablets showed excellent storage stability and highest drug release for its maximum concentration (1:10) with fenofibrate. It is also evident from previous studies that the release profile of the tablet prepared from solid dispersions may be sometimes higher than the solid dispersion due to the presence of super disintegrating agents. It also depends on the pro-portion and properties of the polymer used in the composition of solid dispersion and the proper selection of polymer should be considered.

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Interpretation of release rate constants and Correlation coefficient (R2) values for different release kinetics of Fenofibrate Tablets and Tablets formulated from Solid dispersion: Different release kinetics were studied to find out the release mechanism of fenofibrate from the prepared tablets of the study. Like previous study [22] tablet formulations were also showed highest fitting with Higuchi release pattern that means 17 of 31 formulations fitted with Higuchi, 10 of 31 Korsmeyer and 4 of 31 with First Order Release pattern. In all cases no formulations was fitted with zero order kinetic model of drug release (Table 4). Diffusional exponent or release exponent can also be considered for the characterization of the kinetic models and to determine the mechanism of Fickian transport (case I ) diffusion, Anomalous/ non–Fickian transport (case II)/ zero order transport and super case II transport by diffusion exponent.

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Table 4: Interpretation of release rate constants and correlation coefficient (R2) values for different release kinetics Formulation Code FP188-I(F1) FP188-III(F2) FP188-V(F3) FP188-VII(F4) FP188-X(F5) FP407-I(F1) FP407-III(F2) FP407-V(F3) FP407-VII(F4) FP407-X(F5) FPEG-I(F1) FPEG-III(F2) FPEG-V(F3) FPEG-VII(F4) FPEG-X(F5) FPVP-I(F1) FPVP-III(F2) FPVP-V(F3) FPVP-VII(F4) FPVP-X(F5) FHPMC-I(F1) FHPMC-III(F2) FHPMC-V(F3) FHPMC-VII(F4) FHPMC-X(F5) FMAN-I(F1) FMAN-III(F2) FMAN-V(F3) FMAN-VII(F4) FMAN-X(F5)

Zero Order R2 K0 0.832 1.019 0.817 1.232 0.749 1.343 0.718 1.359 0.720 1.464 0.832 1.019 0.782 1.141 0.771 1.203 0.728 1.304 0.686 1346 0.816 1.087 0.853 1.164 0.822 1.217 0.847 1.318 0.861 1.549 0.816 1.087 0.853 1.164 0.822 1.217 0.847 1.318 0.861 1.549 0.713 0.891 0.747 0.927 0.661 0.962 0.716 1.039 0.671 1.135 0.885 0.800 0.859 0.864 0.862 0.901 0.750 0.877 0.760 0.951

First Order R2 K1 0.9065 -0.0079 0.9164 -0.0109 0.8399 -0.0133 0.8478 -0.0148 0.8611 -0.0309 0.9371 -0.0081 0.8914 -0.0097 0.8841 -0.0106 0.8384 -0.0127 0.8076 -0.0143 -0.005 0.994 0.864 -0.006 0.894 -0.007 0.877 -0.008 0.947 -0.010 0.937 -0.009 0.959 -0.009 0.930 -0.010 -0.011 0.951 -0.018 0.973 0.858 -0.007 0.896 -0.007 0.842 -0.008 0.914 -0.010 -0.016 0.944 0.945 -0.005 0.944 -0.006 0.950 -0.006 0.879 -0.006 0.910 -0.008

Korsmeyer R2 n 0.969 0.474 0.936 0.580 0.885 0.631 0.819 0.632 0.748 0.643 0.422 0.991 0.899 0.542 0.871 0.602 0.822 0.663 0.764 0.688 0.979 0.646 0.839 0.531 0.936 0.398 0.402 0.953 0.944 0.517 0.969 0.442 0.903 0.614 0.863 0.697 0.883 0.808 0.887 0.914 0.289 0.995 0.282 0.991 0.249 0.982 0.261 0.996 0.887 0.914 0.975 0.540 0.406 0.992 0.387 0.989 0.307 0.993 0.921 -0.329

Higuchi R2 0.9703 0.9494 0.9002 0.8899 0.8842 0.9829 0.9446 0.9283 0.893 0.8634 0.9717 0.9363 0.9562 0.9492 0.9696 0.9755 0.9705 0.9463 0.9465 0.9395 0.9271 0.9394 0.8945 0.925 0.8901 0.9925 0.9889 0.9885 0.9463 0.9481

KH 9.1741 10.935 12.115 12.459 13.354 9.120 10.321 10.859 11.891 12.427 6.7832 7.9912 8.6744 9.3487 10.695 9.7799 10.223 10.749 11.464 13.323 8.3616 8.56 9.215 9.7143 10.762 6.9741 7.6285 7.9412 8.1137 8.7461

Comparative Study of Release Profile of Formulated Tablet and Market Products A Comparative study of release profile of formulated tablets and fenofibrate marketed products of six reputed brands of Bangladesh has been revealed by the Bar diagrams which were obtained from the dissolusion studies (Figure 3-8).

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Figure 3: Comparative Study of percent Release of Fenofibrate for Tablet formulated from Pure Fenofibrate, with excipients, Solid dispersion of Poloxamer 188 with excipients and Market Products

Figure 4: Comparative Study of percent Release of Fenofibrate for Tablet formulated from Pure Fenofibrate with excipients, Solid dispersion of Poloxamer 407 with excipients and Marketed Products.

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Figure 5: Comparative Study of percent Release of Fenofibrate for Tablet formulated from Pure Fenofibrate with excipients, Solid dispersion of PEG 6000 with excipients and Marketed Products

Figure 6: Comparative Study of percent Release of Fenofibrate for Tablet formulated from Pure Fenofibrate with excipients, Solid dispersion of PVP with excipients and Marketed Products

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Figure 7: Comparative Study of percent Release of Fenofibrate for Tablet formulated from Pure Fenofibrate with excipients, Solid dispersion of HPMC 6cps with excipients and Marketed Products.

Figure 8: Comparative Study of percent Release of Fenofibrate for Tablet formulated from Pure Fenofibrate with excipients, Solid dispersion of Mannitol with excipients and Marketed Products. After observation of comparative studies, it has been found that the tablet formulated from solid dispersions can show much higher drug release at the same time (60 min) than that of pure fenofibrate, fenofibrate tablet and six marketed products of Bangladesh. This is extremely

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exclusive output from the solid dispersion technique which was the great challenge and promise of the study. CONCLUSION In this study, it was found that the addition of super disintegration agent like SSG to formulations containing

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solid dispersions is a suitable technology to improve the dissolution behavior of poorly water soluble drugs when the drug load is high. However, SSG must be incorporated in the solid dispersion to obtain the desired effect of an increased dissolution rate. The following features are fairly distinguished from the present study: 1. Comparatively tablets formulations from solid dispersion showed the higher drug release than that of solid dispersion formulations due to incorporation of super disintegrating agent. 2. Polymers incorporated in solid dispersion technologies are usually hydrophilic in nature and also showing compatibility with the drug to enhance the drug solubility. The study encompasses the criteria of solvent selection, challenges in formulation of solid dispersion dosage forms, future prospects and various types of marketed preparations containing poor soluble and water insoluble drug. 3. Crystallization is effectively prevented resulting in a higher dissolution rate. Therefore, more extensive in vitro-in vivo correlation (IVIVC) study on similar formulations deemed necessary to establish a successful formulation from biopharmaceutical point of view. Despite many advantages of solid dispersion, issues related to preparation, reproducibility, formulation, scale up, and stability limited its use in commercial dosage forms for poorly water-soluble drugs. Successful development of solid dispersion systems for preclinical, clinical, and commercial use has been feasible in recent years due to the availability of surface-active and selfemulsifying carriers with relatively low melting points. Because of the simplicity of manufacturing and scale up processes, the physicochemical properties and, as a result, the bioavailability of solid dispersions is not expected to change significantly during the scale up. For this reason, the popularity of the solid dispersion system to solve difficult bioavailability issues with respect to poorly water-soluble drugs will grow rapidly. ACKNOWLEDGEMENT The authors would like to acknowledge the support received from the Pharmaceutical Technology Research Laboratory of the Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh.

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