FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETSOF TENOXICAM

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1 Page4074 Indo American Journal of Pharmaceutical Research, 2014 ISSN NO: FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETSOF TENOXICAM Ramesh KVRNS *1, Shahnaz Usman 1, Omar Sarheed 1, Fasiha Shah 1, Tahera Parveen 2, B.VenkataKameswara Rao 2, M.Vinay Kumar 3 1 RAK College of Pharmaceutical Sciences, RAK Medical & Health Sciences University, Ras Al Khaimah, UAE. 2 Julphar Gulf Pharmaceutical Industries, Ras Al Khaimah, UAE 3 Aditya Institute of Pharmaceutical Sciences & Research, India. ARTICLE INFO Article history Received 02/10/2014 Available online 30/10/2014 Keywords Tenoxicam, Solvent Deposited System, Gelucire, Hydroxypropyl Cellulose, Dissolution, Flow Property. ABSTRACT Tenoxicam is a nonsteroidal anti-inflammatory drug belonging to the oxicam group.the drug is slightly soluble in water. In the present investigation, solvent deposited systems of the dispersions of tenoxicam in Gelucire 50/13 (G) and Hydroxypropyl cellulose(hpc) on Microcrystalline cellulose (MCC) were prepared to enhance the dissolution of tenoxicam. Dispersions were prepared employing different proportions of the carriers. The prepared dispersions were characterized by infra-red spectroscopy, x ray diffraction and differential scanning calorimetry. The dispersions exhibited higher dissolution compared to the pure drug and there were no interactions with the carriers. Dispersion in gelucire showed much higher dissolution than the dispersion in hydroxypropyl cellulose. There was an 8 and 4.8 fold increase in dissolution rate and dissolution efficiency respectively with the T-G-MCC (1:2:7) solvent deposited system when compared with the pure drug tenoxicam. When the dispersions were deposited on microcrystalline cellulose it resulted in products with not only much higher dissolution but also having better flow properties enabling easy compression into tablets. Fast dissolving tablets of tenoxicam wereformulated by employing the solvent deposited systems of the dispersions of the drug in gelucire and hydroxypropyl cellulose. All the tablets showed good pharmaceutical characteristics and exhibited rapid dissolution. From the results of the investigation in may be concluded that employing solvent deposited systems of the solid dispersions of tenoxicam is a useful approach to prepare the fast dissolving tablets of tenoxicam. Corresponding author K.V.R.N.S.Ramesh, Professor, RAK Medical & Health Sciences University, Ras Al Khaimah, UAE. venkatramesh@rakmhsu.ac.ae Please cite this article in press as K.V.R.N.S.Ramesh, et al. Formulation and Evaluation of Fast Dissolving Tabletsof Tenoxicam. Indo American Journal of Pharm Research.2014:4(10). Copy right 2014 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 Page4075 INTRODUCTION Tenoxicam is 4-hydroxy-2-methyl-N-(2-pyridyl)-2-Hthieno [2, 3e][1,2] thiazine-3-carboxamide-1,1-dioxide[1]. It is used in the treatment of rheumatoid arthritis and osteoarthritis and employed in the short term management of musculoskeletal disorders. It is administered in a dose of 20 mg daily for 7 days. [2]. It is acrystalline BCS class II drug and is very slightly soluble in water (0.045 mg / ml)[1]. Drugs with low solubility show poor bioavailability after oral administration and their absorption is dissolution rate limited. Poorly soluble compounds when converted into high energy amorphous forms demonstrate improved dissolution when compared to the crystalline state [3]. There are reports that amorphous compounds with their enhanced dissolution exhibit enhanced bioavailability [4-6] as their absorption is dissolution rate limited. Of the various approaches employed to enhance the dissolution of poorly soluble drugs, solid dispersion technology continues to be the most widely employed technique because of ease of preparation and the variety of polymers that can be utilized. Some of the polymers used include polyvinylpyrrolidone (PVP), poloxamer, hydroxypropyl methylcellulose (HPMC), polyethylene glycols (PEGs) etc. There are some reports on the dissolution enhancement of tenoxicam by employing solid dispersions and co- precipitates using polyvinyl pyrrolidone [7], sorbitol [8], sodium benzoate [8], and L-arginine [9] The aim of the present investigation is to employ solid dispersions and solvent deposited systems of tenoxicam to prepare fast dissolving tablets. Gelucire (50/13) [G] and hydroxypropyl cellulose (HPC) were used to prepare the solid dispersions and microcrystalline cellulose (MCC) was used as a substrate to deposit the solid dispersions to prepare the solvent deposited systems. Solid dispersion systems prepared many times are unhandable and cannot be easily converted into tablets. So the other major objective of the study is to modify the solid dispersion systems of tenoxicam into free flowing forms suitable for direct compression. MCC is incorporated not only to prepare a solvent deposited system with higher dissolution of the drug but also to improve the flow properties of the prepared dispersions for easy compression and also to increase the bulk of the prepared dispersion as tenoxicam is a low dose drug. MATERIALS AND METHODS Materials Tenoxicamwas a gift sample from Julphar Gulf Pharmaceutical Industries, UAE; Gelucire (50/13) [G] was obtained as a gift sample fromgenova Life Sciences, Bangalore, India. Hydroxypropyl cellulose SL (HPC) Nisso: having a viscosity of cps in a 2% aqueous solution at 20 o C, microcrystalline cellulose (Avicel, FMC Type ph 105), and methanol procured from commercial sources were used. All other chemicals and solvents used were of analytical grade. Methods Preparation of solid dispersions of tenoxicam Solid dispersions were prepared by solvent method. Solid dispersions of tenoxicam (T) in gelucire (G) and hydroxypropyl cellulose (HPC) were prepared in different ratios as shown in Table 1. Tenoxicam (900 mg) was dissolved in 100 ml of methylene chloride. To the clear solution of the drug, gelucire (100 mg) or HPC (100mg) were added and stirred to dissolve. MCC was then dispersed as fine particles in the solution and the solvent was removed under vacuum and the mass obtained was scrapped and dried in a desiccator over anhydrous calcium chloride overnight and was crushed, pulverized and sifted through mesh No. 100 and stored in a desiccator until further use. In case of dispersions employing HPC the solvent system was a mixture of methylene chloride and methanol (1:1). Preparation of physical mixtures Physical mixtures of T-G and T- HPC in a ratio of 1:1 were prepared by mixing thoroughly the accurately weighed quantities of tenoxicam and the carriers by trituration in a mortar and sifted through mesh No Evaluation of solid dispersions Drug content uniformity From each batch, four samples of 50 mg each were taken and analyzed for tenoxicam content. 50 mg of solid dispersion was weighed into a 50 ml volumetric flask. 40 ml of methanol was added and contents were thoroughly mixed to dissolve tenoxicam from the solid dispersions. The solution was made up to volume with methanol and suitably diluted with phosphate buffer of ph 7.4and assayed for tenoxicam content by measuring the absorbance at 368 nm using phosphate buffer of ph 7.4 as blank. The results are given in Table 1. Dissolution studies The dissolution tenoxicam in pure form and from various solid dispersions was studied using USP Type I dissolution rate test apparatus (Lab India Model DISSO) employing a paddle stirrer. In 900 ml of dissolution medium(phosphate buffer of ph 7.4), a sample equivalent to 20 mg of tenoxicam was added and a speed of 50 rpm and a temperature of 37 o C ± 1 o C were employed in each test. A 5 ml aliquot of dissolution medium was withdrawn at different time intervals, filtered, suitably diluted and assayed spectrophotometrically at 368 nm using Labomed Model UVD 2950 spectrophotometer. The percent of tenoxicam dissolved at various time intervals was calculated and plotted against time. The results are given in Table 1 and shown in Fig. 1 & 2

3 Page4076 X-ray diffraction studies X-ray powder diffraction patterns of tenoxicam and its solid dispersions were obtained by using X-ray powder diffractometer, PANalytical, Model No. X Pert pro employing Cu K α radiation. The diffractograms were run between 2 o and 40 o at 2 o /min in terms of 2θ angle. The operation data were as follows: generator tension (voltage) 40 kv; generator current 30 ma. The diffractograms of tenoxicam and various solid dispersions are shown in Fig.3. DSC Studies Tenoxicam and the solid dispersions were subjected to differential scanning calorimetric analysis to know about the physical state of the drug in the dispersion and any interaction between the drug and carriers. The calorimeter (TA Instruments, Bangalore Model Q 20)was operated at a scanningrate of 10 O Cper minute and heated between 25 O C to 400 O C.The samples were sealed in aluminum pans and heated in a constant inert atmosphere maintained by purging nitrogen gas at a flow rate of 10 ml/min. The thermograms obtained on various products are shown in Fig. 4. FTIR studies Tenoxicam and the solid dispersions prepared were subjected to FTIR analysis using Fourier transform infrared spectrophotometer (Agilent Model Cary 630). Attenuated total reflectance (ATR) sampling interface was used to obtain the spectra. The IR spectra are shown in Fig. 5. Determination of solubility The solubility of tenoxicam in distilled water alone and in the presence of gelucire and hydroxypropyl cellulose was determined. An excess amount of tenoxicam was placed in tightly closed bottles containing 100 ml of distilled water (ph6.8) or distilled water containing 1% gelucire or HPC. The bottles were thoroughly shaken at 120 rpm for 48 hoursat25±1 O C. At the end of this period the solutions were filtered and the filtrate was collected into dry containers. The solutions were suitably diluted and assayed for tenoxicam content. Evaluation of flow properties of dispersions The flow properties of the prepared dispersions were evaluated bydetermining the bulk density, tapped density, compressibility index (Carr index), angle ofrepose and Hausner ratio. The flowability and compaction behavior of the dispersions werealso studied by using Kawakita plot. The details of flow properties are given in Table 2. Construction of Kawakita Plot 5 grams of tenoxicam or the prepared product was weighed accurately and transferred to a measuring cylinder. The initial volume V o wasnoted. The measuring cylinder was now subjected to standard tapings of 10, 20, 30, 40, 50 and 60 and the reduction in volume of the powder bed was noted after each set of tapings. Kawakita et al [10] studied about the flowability and compaction behavior of powders. Kawakita plot was used to analyze the behavior of powder from the bulk density state to the tapped density state. The reduction in volume after tapping (using measuring cylinder) was noted. The plot of number of tapings (n) vs the degree of volume reduction (n/c) was plotted and the values of a and b was calculated by using equation: n/c = n/a+1/ab where, n is the number of tapings and 'c' is the degree of volume reduction equal to c = (V 0 -V)/V 0 where, V 0 is initial volume before tapping and V is volume after taping, a and b are constants. The constants of Kawakita equation can be used to estimate the flow and cohesiveness properties of powders. Constant a, describes the compressibility and constant 1/b describes cohesive properties of powders. The constants a and b of Kawakita plot were determined (Table 3) from the slope and intercept of the plot of n/c versus number of tapings. Formulation of tablets Preparation of fast dissolving tablets containing solid dispersions of tenoxicam Fast dissolving tablets containing 20 mg of tenoxicam were prepared by direct compression method and the formulae used in the study are shown intable 4. Two different superdisintegrants sodium starch glycollate and croscarmellose were used. The dispersion equivalent to 20 mg of tenoxicam was mixed in geometric proportions with theother ingredients of the formula and the blend was screened and compressed on Cadmach rotary punching machine Evaluation of Fast Dissolving Tablets All the tablets were evaluated for different parameters such as hardness, uniformity of weight, friability, disintegration time and in vitro dissolution study. The prepared tablets were kept for accelerated stability studies (resultsare not included in this investigation ).

4 Page4077 Hardness Hardness of the tablets was determined using the Monsanto hardness tester. The lower plunger was placed in contact with the tablet and a zero reading was taken. The plunger was then forced against a spring by tuning the threaded bolts until the tablet fractured. Then the final reading was recorded. The hardness was computed by deducting the initial reading from the final reading. Uniformity of Weight The uniformity of weight of the tablets was determined by weighing 20 tablets individually and determining the average weight and the standard deviation. Friability The Roche friability test apparatus was used to determine the friability of the tablets. Twenty tablets were selected, de-dusted and weighed. Then these were placed in a drum and rotated for 100 times in 4 minutes. The tablets were de-dusted to remove any loose dust and were re-weighed. The percentage friability was calculated by the formula. Percent friability = [initial wt. - final wt. / initial wt.] x 100 The details of hardness, friability and weight, and disintegration time are given in Table 5. Disintegration and dissolution study of tablets The disintegration test of tablets was performed as per compendial guidelines employing disintegration test apparatus. The dissolution study of the formulated tablets is performed as per the procedure previously described for the dispersions. The results of the dissolution studies of the formulated tablets are given intable 6 and shown in Fig.7 RESULTS AND DISCUSSION All the dispersions prepared were found to be fine and free flowing. However there is a marked improvement in the flow properties (discussed in detail latter) of the dispersion deposited on microcrystalline cellulose compared with the dispersions prepared employing gelucire or hydroxypropyl cellulose. Low s.d. values in the percent drug content ensured uniformity of drug content (Table1) in each batch. The solid dispersions gave fast and rapid dissolution when compared to pure drug tenoxicam and the physical mixtures(fig.1&2). Table 1 Drug Content and Dissolution Parameters of various Solid Dispersions. Solid Dispersion Tenoxicam content T 50 D.E 30 K 1 Cube root dissolution (% ) (min) (%) (min -1 ) rate constant (r 2 ) (mg 1/3 min -1 ) (r 2 ) Tenoxicam -- > (0.977) (0.912) T-G (1:1) 49.75± (0.981)0.015 (0.899) (PM) T-HPC (1:1) ± (0.935)0.010 (0.902) (PM) T-G (1:1) ± (0.944)0.022 (0.918) T-HPC (1:1) ± (0.965)0.017 (0.922) T-G (1:2) ± (0.957)0.043(0.934) T-HPC (1: 2) ± (0.976) (0.914) T-G-MCC ± (0.966) (0.908) (1:2:7) T-HPC -MCC ± (0.982) (0.921) (1:2:7) PM Physical Mixture;D.E. Dissolution Efficiency

5 Page4078 Fig 1 Dissolution profiles of various solid dispersions. Fig 2 Dissolution profiles of various solid dispersions and solvent deposited systems. As the proportion of the carrier gelucire or hydroxypropyl cellulose is increased there is also an increase in the dissolution rate. But the proportion of the carrier could not be increased beyond 1:2 ( drug : carrier ) as with increased amount of carrier, the dispersion became less free flowing and also is found to be sticky and less handable. Since the prepared dispersion needs to be converted into a dosage form such as a tablet and as such the dispersion should possess good flow characteristics, so the dispersions were converted into a solvent deposited system by depositing the product on microcrystalline cellulose. The objective of this modification is to serve 2 purposes a. to increase the flow property of the dispersion by obtaining discrete particles of the dispersions avoiding any aggregates andb. to further improve the dissolution of tenoxicam due to enhanced surface area upon deposition on microcrystalline cellulose.when gelucire or HPC alone were used as carriers, at 1:2 ratio, about 6 and 3 fold increase in the dissolution rate of tenoxicam was observedrespectively. But solvent deposited system employing combined carriers G MCC or HPC MCC gave much higher dissolution ratesthan the dispersions prepared in individual carriersalone. The solvent deposited system prepared by employing gelucire (1:2:7) gave highest dissolution rate ( min -1 ). The dissolution efficiency as described by Khan[11],was also increased from 16.66% for the pure drug to 80.12% in case of T-G-MCC and % in case of T-HPC-MCC. The dissolution of tenoxicam in pure form and from various solid dispersions obeyed Hixson Crowell 12 cube root dissolution rate equation and hence this equation (givenbelow)was used to obtain corresponding dissolution rate constants and shown in Table 1. (W o ) 1/3 -(W t ) 1/3 = K.t where W o is initial mass and W t is the mass remained at time t. The cube root equation is applicable to the dissolution of powders which are monodisperse consisting of uniform sized particles. A plot of (W o ) 1/3 -(W t ) 1/3 versus time will be linear when dissolution occurs from monodisperse and discrete particles of uniform size. Ideally the dissolution should occur from particles which are discrete and non-aggregating. The aim of solvent deposition of the dispersion onmcc in this work is obtain discrete particles. The Hixson Crowell plots were found to be linear in all the solvent deposited systems prepared indicating that dissolution is probably

6 Page4079 occurring from discrete and uniform sized particles. So deposition of the solid dispersions on MCC has resulted in more uniform particles. The correlation coefficient values are given in Table 1. The r 2 values obtained for the first order kinetics are found to be higher than that of Hixson Crowell cube root model so the drug dissolution is probably occurring majorly by first order process. To evaluate the mechanism of involved in the increased dissolution rate of tenoxicam from the solid dispersions, solubilityand x ray diffraction studies were carried out. The solubility of tenoxicam was found to be mg/ml, 0.71mg/ml and mg/ml in distilled water and in distilled water containing 1% gelucire and 1% HPC respectively. This increased solubility could be attributed to the hydrophilic nature of the 2 carriers which makes the hydrophobic tenoxicam more wetted resulting in increased solubility and dissolution. This higher dissolution of tenoxicam fromthe dispersions couldalso be becauseof the presence of drug in more amorphous form. The x-ray diffractograms of gelucire, HPC, pure drug tenoxicam and the dispersions are shown in Fig.3. It can be seen that the pure drug (A), which is highly crystalline as evident from the sharp diffraction peaks is converted into an amorphous form in the solid dispersions, as the crystalline peaks have significantly disappeared. Thus gelucire and HPC are inhibiting the recrystallization of tenoxicam during the preparation of the dispersions.that the drug might be existing in an amorphous form is also evident from the DSC studies. The thermograms of tenoxicam and the dispersions are shown in Fig4. The endotherm of pure drug tenoxicam showed a sharp peak at 222 o C which is due to its melting point. Gelucire (50/13) showed its endothermic peak around 49 o C and the endothermic peak due to softening was observed at around 80 o C in case of HPC. A small endothermic event occurred at C which could be due to the decomposition of HPC. Whereas the sharp endothermic peak expected of tenoxicam inthe dispersions disappeared almost completely. This could be due to the presence of the drug in soluble amorphous state in the polymersand loss of crystallinity.this finding is in agreement with Agnivesh et al [13] who reported that disappearance of the characteristic peaks of the valsartan dispersed in gelucire (50/13) is due to melting of the drug in the matrix. Thisloss of crystallinity and presence in soluble state resulted in faster dissolution of tenoxicam from the solid dispersions. In addition other factors such as possible reduction in particle size, absence of aggregation and agglomeration and easy dispersibility of tenoxicam dispersion in the dissolution medium might also have contributed to the increased dissolution rate and efficiency.

7 Page4080 Any possibleinteraction between tenoxicam and the excipients gelucire and hydroxypropyl cellulose was verified by comparing the IR spectra of pure tenoxicam with that of dispersions. The IR spectra are shown in Fig 5. Pure tenoxicam (A) exhibited characteristic peaks at 3119 cm -1 and 3092 cm -1 ( N-H and O-H stretching ), 1638 cm -1 ( aromatic C=C stretching ), 1598 cm -1 and 1530 ( Amide C = O, C=N - ), 1436 cm -1 (C-H deformation ), 1388 cm -1 ( - CH 3 deformation ). The solid dispersion (B) in gelucire (50/13) and hydroxypropyl cellulose (C) also exhibited the characteristic peaks of tenoxicam indicating retention of chemical identity of tenoxicam. Hence, there was no interaction between the drug and the carriers used to prepare the dispersions in the study.

8 Page4081 The dispersions should be easily handled during manufacture, while they are being converted into tablets. This characteristic of ease of handling is evaluated from the study of the flow properties of the prepared dispersions. The flow properties of the various dispersions prepared were studied by determining the bulk density, tapped density, compressibility index (Carr index), angle of repose and Hausner ratio. The values are reported in the Table 2. The data given in the table indicates that the flow properties of the T-G or T-HPC dispersions as such are not very satisfactory. This could be because of the waxy nature of gelucire and inherent poor flow property of HPC. But however the flow properties of the solvent deposited systems have markedly improved. This clearly showed that the dispersions deposited on MCC possessed good flowability and as such can be more easily handled during the process of tableting by direct compression. Table 2 Flow Properties of Solid Dispersions and Solvent Deposited Systems. Property T T-G T-HPC T-G-MCC T-HPC-MCC (1:2) (1:2) (1:2:7) (1:2:7) Bulk Density 0.35± ± ± ± ±0.03 (g/cm 3 ) Tapped Density 0.66± ± ± ± ±0.07 (g/cm 3 ) Carr index 46.39± ± ± ± ± 0.97 Hausner ratio 1.86± ± ± ± ±0.09 Angle of repose 37.45± ± ± ± ±1.55 Kawakita plot The flowability and compaction behavior of the powders was also studied by using Kawakita plot [10].Plots of n/c against the number of tapings (n) as shown in Fig 6gave a fairly linear relationship with correlationcoefficient values of more than Values of a, i.e. the maximum volume reduction after tapping, obtainedfrom the slope of the straight lines are given in Table 3. The rank order of values of a is T-G (1:2) > T-HPC (1:2)> T-G-MCC (1: 2: 7)>T-HPC-MCC (1: 2: 7). A low value of a indicates that thepowder system has packed more densely on initial pouring intothe cylinder, which implies that the powders were well packedbefore tapping, and tapping will not result in a considerable change in their packing. I l i c [ 1 4 ] in their study onpowder particle rearrangement suggested that powders with values of a less than 0.21 have good flowability while those greater than 0.41 have poor flowability. The solvent deposited systems T G-MCC and T-HPC-MCC gave values of a of and respectively.so as such the deposition of the dispersions on MCC has improved their flow nature and the observed values of a of the solvent deposited systems are quite close to the above reported values Ilic et al., whereas the values of a of the dispersions in gelucire and HPC exhibited quite high values of a of and Also the value of b fordispersions withoutmcc is lower implying that the cohesiveness of these powdersis higher than the powders obtained by solvent deposited systems. The high values of b (low value of 1/b) in solvent deposited systems(0.051&0.058) are indicative of good flowing powders which are more easily directly compressed. Yamashiro et al [15]have in their work reported that the reciprocal values of b will increase with increasing adhesion between the particles. So as such since the solvent deposited systems exhibited favorable flow properties they are employed.in the preparation of tablets. Fig 6 Kawakita plot for various solid dispersions and solvent deposited systems.

9 Page4082 Table 3 Values of a and b from Kawakita plot. Solid Dispersion T-G (1:2) T- HPC (1:2) T-G-MCC (1:2:7) T-HPC-MCC (1:2:7) a b R The post compression properties of the tablets formulated are also evaluated. The composition of various fast dissolving tablets formulated is shown in Table 4. The various prepared tablets were evaluated with respect to their hardness, friability, drug content and weight uniformity and the respective values are shown in Table 5. The hardness of tablets of all formulations was in the range of 2.99 to 3.87 kg/cm 2. The friability of tablets of all formulations wasless than 1 %. The tablet formulations in all the prepared batches containedtenoxicam within 100 ± 5% of expected content. As such, all the batches of the fabricated tablets were of good quality with regard to hardness, friability and drug content. All tablets are found to be uniform in weight with low standard deviation.the dissolution of tenoxicam from the formulated tablets is found to be fast. More than 90 % of the drug has dissolved(fig7)within 30minutes from the tablets prepared by employing the solvent deposited systems of tenoxicam. In between the tablets prepared by employing either the gelucire or HPC dispersions the gelucire dispersions exhibited muchhigher dissolution rate values, shown in Table 6. This could be because of higher solubility of tenoxicam in the presence of gelucire. Table 4 Composition of Fast Dissolving Tablets Formulated Employing Solvent Deposited Systems. Ingredient F1 F2 F3 F4 (in mg) T-G-MCC (1:2:7) (Equivalent to 20 mg of Tenoxicam)s T-HPC-MCC (1:2:7) (Equivalent to 20 mg of Tenoxicam) Sodium Starch Glycollate Crosscarmellose Ludipress Talc Magnesium stearate Table 5 Drug content, Hardness, Weight, Friability and Disintegration Time of Different Formulations. Formulation Drug Content a Hardness b Weight c Friability d DT e (%) (kg /cm 2 ) (mg) (%) (sec) F ± ± ± ± ± 0.87 F ± ± ± ± ± 0.35 F ± ± ± ± ± 0.42 F ± ± ± ± ± 0.87 a- mean ± ( n = 10) b- n = 5 c- Mean ± ( n = 20) d- n = 20 e- n = 6 DT Disintegration Time Table 6 Dissolution Parameters of Fast Dissolving Tablets Formulated. Formulation (min). F1 F2 F3 F4 T 90 (min -1 ) (%) K 1 Efficiency Dissolution

10 Page4083 Fig 7 Dissolution profiles of various tablet formulations. CONCLUSIONS Fast dissolving tablets of tenoxicam could be designed by employing solvent deposited systems of the dispersions of tenoxicam in gelucire (50/13) and hydroxypropyl cellulose.the dispersion of tenoxicam in gelucire and HPC reduced the crystallinity of tenoxicam and there are no interactions between the drug and the carriers used. Increasing the proportion of the carrier also increased the dissolution rate however with higher proportion of carrier the dispersions became sticky and unhandable. The dispersions deposited on microcrystalline cellulose exhibited good flow properties to enable easy and convenient manufacture of tablets and also the dissolution rate is significantly increased. Tablets prepared employing T-G-MCC (1:2:7)system gave much higher dissolution than T-HPC-MCC (1:2:7). Thus fast dissolving tablets of tenoxicam could be designed employing the solvent deposited systems of tenoxicam. The future research in this area should focus on the utility of various other carriers for the solvent deposited systems. ACKNOWLEDGEMENT The authors express their gratitude to the Vice Chancellor of RAK Medical & Health Sciences University and the Dean of RAK College of Pharmaceutical Sciences for the encouragement and facilities provided. The authors also express their thanks to Dr.Sunil Dhaneshwar and Dr.Bhoomendra Bhongade of RAKMHSU for their help in the IR Spectral studies. The services of the Central Instrument Facility at Andhra University, India for obtaining the XRD and DSC data are gratefully acknowledged. Author s statements Competing interests - the authors declare no conflict of interest List of Abbreviations G - Gelucire (50/13) HPC - Hydroxypropyl cellulose MCC Microcrystalline cellulose T-G Tenoxicam Gelucire T-HPC Tenoxicam Hydroxypropyl cellulose T-HPC- MCC - Tenoxicam Hydroxypropyl cellulose Microcrystalline cellulose T-G-MCC - Tenoxicam Gelucire Microcrystalline cellulose REFERENCES 1. Maryadale J. O Neil ( Edi) Merck Index, 14 th ed, published by Merck Research Laboratories, division of Merck & co,2006 ; p Lexicomp Drug Information Handbook, 21 st Ed., published by Lexicomp, Ohio, 2012; p Yu L.. Amorphous pharmaceutical solids: Preparation, characterization and stabilization, Adv Drug Delivery Rev2001; 48: Willart JF, DescampsM., Solid state amorphization of pharmaceuticals, Mol Pharm2008; 5: Leuner C., Dressman J., Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 2000 ; 50: JanssensS., Van den Mooter G., Physical chemistry of solid dispersions, 2009 ; J Pharm Pharmacol 61: Manal K. Darwish., Manal M. Foad., Enhancement of the dissolution profile of Tenoxicam by a solid dispersion technique and its analytical evaluation using HPLC,Drug Discov Ther. 2009; 3(1): Omaima N. El-GazayerlyCharacterization and Evaluation oftenoxicam Coprecipitates, Drug DevInd Pharm 2000 ; 26(9) :

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