INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH AND BIO-SCIENCE

INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH AND BIO-SCIENCE FORMULATION AND EVALUATION OF PAROXETINE HYDROCHLORIDE ORODISPERSIBLE TABLETS USING TAPIOCA STARCH A. BHARATHI *, K N V DEEPTHI, S. BHAGYA LAKSHMI, RAMCHANDRA KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada-520 010, Andhra Pradesh, India Accepted Date: 07/12/2014; Published Date: 27/02/2015 Abstract: Paroxetine hydrochloride is a potent selective serotonin reuptake inhibitor (SSIR) used as an antidepressant. The present investigation involved in preparing and evaluating Paroxetine hydrochloride orodispersible tablets. The present study also involved in introducing and evaluating the super disintegrant action of a natural excipient tapioca starch. Orodispersible tablets of paroxetine hydrochloride were prepared using tapioca starch in different strengths 2.5%, 5%, 7.5%, 10% as superdisintegrant by direct compression and evaluated. Tablets were also prepared by using crospovidone and sodium starch glycolate (in strengths 2.5%, 5%, 7.5%, 10%) as superdisintegrants for comparision. Effect of diluents like dicalcium phosphate and D-mannitol was also evaluated. Flow propertie of powder blends were evaluated. All the formulations prepared were evaluated for post compression parameters like hardness, friability, weight variation, disintegration time and results were found to be within good limits. Paroxetine hydrochloride ODT tablets (200mg) were prepared employing tapioca starch disintegrated within 30sec showing rapid and maximum release of drug in 5min when compared to those tablets prepared by using other synthetic super disintegrants. Tablets containing dicalcium phosphate as diluent shown better results compared to that of D-mannitol. Thus tapioca starch, a natural excipient was found to be promising superdisintegrant in preparation of orodispersible tablets effectively in the strengths of 2.5%, 5%, 7.5%, 10%. Keywords: Paroxetine hydrochloride ODT, Tapioca starch, Crospovidone, Sodium starch glycolate, Dicalcium phosphate, D-mannitol. Corresponding Author: MS. A. BHARATHI Access Online On: www.ijprbs.com PAPER-QR CODE How to Cite This Article: 36

INTRODUCTION Orodispersible tablet dosage form is an useful dosage form for geriatrics, pediatrics, mentally disabled, bed-ridden and patients those experience dysphasia. It does t require water for swallowing. Due to pregastric absorbtion of drug it may also avoid first-pass metabolism 1. European Pharmacopoeia 2 has used the term orodispersible tablet for tablets that disperse readily and within three minutes before swallowing. The US Food and Drug Administration, Center for Drug Evaluation and Research (CDER) defines, in the Orange Book, an ODT as A solid dosage form containing medicinal substances, which disintegrates rapidly, usually within a matter of seconds(30sec), when placed upon the tongue 3. Paroxetine 4,5,6 belongs to selective serotonin reuptake inhibitor category. It is used to treat major depression, obsessive-compulsive disorder, panic disorder, social anxiety, posttraumatic stress disorder, generalized anxiety disorder and vasomotor symptoms (e.g. hot flashes and night sweats) associated with menopause in adults. It undergoes extensive first pass metabolism in liver. Some patients have difficulty in swallowing and are less like to continue dosage regimen. Navvaro et al 7 found that orodispersible type of tablets may improve patient compliance for depressive patients who undergo swallowing difficulties, nausea, limited liquid intake and also preffered for patients without these difficulties. There are synthetic excipients like crospovidone, croscarmellose sodium, sodium starch glycolate used as superdisintegrants. Natural excipients like banana powder, sago starch, corn starch, rice starch, yam starch, potato starch were also tried as superdisintegrants 8,9. But less or no works were reported using tapioca starch as superdisintegrant, a natural excipient which is mostly available in various parts of the world, having nutritional values, cost effective 10,11. In the present study an attempt was made to introduce tapioca starch, a natural excipient as superdisintegrant in the preparation of orodispersible tablets of paroxetine hydrochloride by direct compression and evaluate for its activity. The disintegrant action of tapioca starch was also compared with synthetic superdisintegrants like crospovidone, sodium starch glycolate. The present study also involved in evaluating effect of diluents like dicalcium phosphate, D- mannitol on tapioca starch activity. The results of the present investigation were reported in the following sections of this paper. MATERIALS AND METHODS Materials: Paroxetine hydrochloride was a gift sample from Aurobindo Pharma Limited. Tapioca starch was a gift sample from Life line formulations, Vijayawada. Crospovidone, sodium starch 37

Absorbance at 292 nm Research Article CODEN: IJPRNK ISSN: 2277-8713 glycolate, D-mannitol, dicalcium phosphate, magnesium stearate, talc were procured from S.D. Fine chemicals Ltd, Mumbai. All other materials used were of analytical grade. Methods: Analytical method An UV-VIS spectrophotometric method was used for the estimation of Paroxetine hydrochloride in this work. A stock solution of Paroxetine HCl (1000µg/mL) was prepared in methanol and the absorbance of Paroxetine hydrochloride was measured at 292nm using Elico UV-VIS spectrophotometer SL 150. As the dissolution studies were carried out in 0 N HCl buffer 12, the standard concentrations were prepared using the same medium for dilution in the range of 2-10µg/mL of drug which obeyed Beer s law and calibration curve was constructed. The calibration data was given in table 1 and curve was shown in figure 1. Table 1 : Calibration curve data of Paroxetine Hydrochloride in 0N HCl buffer Concentration (μg/ml) Absorbance at 292nm 2 0.038 4 0.064 6 0.087 8 011 10 036 05 0 y = 0.0122x + 0.0143 R² = 0.9997 0 0 0 2 4 6 8 10 Concentration(µg/mL) Figure 1 : Calibration curve of Paroxetine Hydrochloride in 0N HCl buffer 38

Compatibility Study Characterization by FTIR spectroscopy- Drug Excipient Compatibility was investigated by Fourier transform infrared (FTIR) spectroscopy. The samples for FTIR were prepared by KBr disc method. The infrared spectra of pure drug paroxetine hydrochloride, drug with excipients were collected over a spectral region from 4000 to 1000 cm -1. The characteristic peaks of drug were also found in optimized formula which indicated the absence of interactions between drug and excipients (table 2 and figure 2, 3). Table 2: FTIR spectral wave numbers and functional groups of Paroxetine Hydrochloride FUNCTIONAL GROUP PRESENT PEAK OBSERVED AT WAVE NUMBER(cm -1 ) Amine N-H Aromatic Bending C-O stretching C-N Aryl C=C 3500-3100 900-690 1300-1000 1350-1000 1600-1475 Fig 2: FTIR Spectrum for Paroxetine Hydrochloride pure drug 39

Fig 3: FTIR Spectrum for Optimized formulation (F3) Preparation of ODTs of Paroxetine hydrochloride Direct compression method was used due to ease of manufacture, product stability and high efficiency, easy to scale up, cost effectiveness of the method. Compressed tablets of Paroxetine Hydrochloride using different superdisintegrants were prepared by direct compression method, as per formulae given in tables 3, 4. Accurately weighed quantities of drug (equivalent weight i.e., 44.4mg), super disintegrant were passed through sieve no #40 and remaining ingredients were added to the blend in a polybag and mixed homogeneously for 10 minutes. Sufficient quantities of diluent (Dicalcium phosphate/d-mannitol) was used to raise the total bulk of the tablet to a weight of 200mg each. The resulting powder blend was compressed on 8 station punching machine (ELITE mini press) using 7 mm round punches to the hardness of 3-3.5 kg/cm 2. Table 3: Formulae of Orodispersible Tablets of Paroxetine Hydrochloride using DCP as diluent Formulation Ingredients Quantity of Ingredients(mg) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12 Paroxetine HCl 44.4 44.4 44.4 44.4 44.4 44.4 44.4 44.4 44.4 44.4 44.4 44.4 Tapioca starch 5 10 15 20 - - - - - - - - 40

Crospovidone - - - - 5 10 15 20 - - - - Sodium glycolite starch - - - - - - - - 5 10 15 20 DCP 142.6 137.6 132.6 127.6 142.6 137.6 132.6 127.6 142.6 137.6 132.6 127.6 Magnesium stearate 4 4 4 4 4 4 4 4 4 4 4 4 Talc 4 4 4 4 4 4 4 4 4 4 4 4 Saccharin q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s Total 200 200 200 200 200 200 200 200 200 200 200 200 Table 4: Formulae of Orodispersible Tablets of Paroxetine Hydrochloride using D-mannitol as diluent Formulation Quantity of Ingredients(mg) Ingredients F13 F14 F15 F16 F17 F18 F19 F20 F21 F22 F23 F24 Paroxetine HCl 44.4 44.4 44.4 44.4 44.4 44.4 44.4 44.4 44.4 44.4 44.4 44.4 Tapioca starch 5 10 15 20 - - - - - - - - Crospovidone - - - - 5 10 15 20 - - - - Sodium glycolite starch - - - - - - - - 5 10 15 20 D-mannitol 142.6 137.6 132.6 127.6 142.6 137.6 132.6 127.6 142.6 137.6 132.6 127.6 Magnesium stearate 4 4 4 4 4 4 4 4 4 4 4 4 Talc 4 4 4 4 4 4 4 4 4 4 4 4 Saccharin q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s Total 200 200 200 200 200 200 200 200 200 200 200 200 EVALUATION Precompression parameters were carried out for powder blends like Angle of repose, Bulk density, Tapped density, Carr s index, Hausner s ratio as per pharmacopoeia methods 13. Postcompression parameters like thickness, hardness, friability, weight variation, drug content, wetting time, in-vitro disintegration time, in-vitro dissolution studies were carried out for compressed tablets as per pharmacopoeia methods 14. 41

Thickness: Thickness was measured using Vernier calipers. Hardness: Hardness of tablets was measured using Monsanto hardness tester. Weight variation: Randomly selected twenty tablets were weighed collectively and individually using digital balance. Then the individual weight was compared with average weight. Friability: The Roche friability test apparatus was used to determine the friability of the tablets. Wetting time: Five circular tissue papers of 10cm diameter are placed in a petridish. Ten milliliters of water soluble dye solution is added to petridish. 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 the wetting time. In-vitro disintegration time: Six tablets were collected randomly and introduced each tablet into each tube of tablet disintegrating apparatus. Suspended the assembly in the beaker containing a medium of 900ml of water at temperature 37± 0.5 0C. Operated the disintegration apparatus and the time required for complete dispersion of a tablet was measured. In vitro Dissoluion studies: In vitro dissolution of orally disintegrated tablets of Paroxetine was studied in USP type-ii dissolution apparatus employing a paddle stirrer at 50 rpm. 900 ml of 0N HCl was used as dissolution medium. The temperature of dissolution medium was maintained at 37± 0.5 0C throughout the experiment. One tablet was used in each test. Samples of dissolution medium (5ml) were withdrawn by means of syringe fitted with pre-filter at known intervals of time and analyzed for drug release by measuring the absorbance at 292 nm. The volume withdrawn at each time interval was replaced with fresh quantity of dissolution medium. The dissolution studies were carried out in triplicate and the results were given in mean ± standard deviation values. 42

In-vitro release kinetics: Dissolution data of above formulations was fitted in Zero order, First order equations. Zero-Order Kinetics- Zero order as cumulative amount of drug released vs time, C = K 0 t Where K 0 is the zero-order rate constant expressed in units of concentration/time and t is the time in hours. A graph of concentration vs time would yield a straight line with a slope equal to K 0 and intercept the origin of the axis. First order kinetics- First order as log cumulative percentage of drug remaining vs time, l o g C = l o g C 0 K t / 2.303 Where C 0 is the initial concentration of drug, K is the first order constant, and t is the time. RESULTS AND DISCUSSION Paroxetine orodispersible tablets were prepared by direct compression method according to the formulae showed in tables 3, 4. Evaluation parameters were performed in triplicate and the results were given in mean ±SD values. Pre compression parameters were performed inorder to evaluate the flow properties of powder blend. The results of various pre compression parameters were furnished in tables. The Angle of repose of the powder blend of drug and excipients was found to be (< 25 0 ) indicate excellent flow properties. Compressibility (%) index or Carr s index values ranged from 1 to 18.3 %. The Hausner s ratio values ranged from 114 to 196. The values of angle of repose, Hausner s ratio, Carr s index indicate the good flow property of powder blend of drug, excipients according to the specifications mentioned in USP. The results were furnished in tables 5, 6. 43

Table 5: Pre compression properties of formulations (F1-F12) containing DCP as Diluent Parameters Formulation code Bulk Density(ρ b ) gm/cc Tapped Density(ρ t ) gm/cc Angle of Repose(θ) Carr s index (%) Hausner s ratio F1 0.674±0.004 0.786±0.003 27.41±0.47 14±09 16±0.004 F2 0.686±0.006 0.782±0.002 25.72±0.43 12±5 139±0.003 F3 0.694±0.003 0.795±0.003 25±0.52 12.7±2 146±0.004 F4 0.694±0.005 0.788±0.001 26.3±0.025 11.9±07 135±0.005 F5 0.642±0.003 0.732±0.002 27.6±0.45 12.3±2 140±0.002 F6 0.636±0.007 0.769±0.003 25.5±9 17±06 133±0.001 F7 0.645±0.005 0.714±0.005 24.3±8 10.9±7 122±0.003 F8 0.656±0.003 0.731±0.006 28.7±3 15±08 114±0.004 F9 0.664±0.002 0.755±0.001 27.6±3 12±05 137±0.001 F10 0.681±0.001 0.759±0.003 24.67±0.51 1±3 114±0.004 F11 0.665±0.002 0.789±0.005 24.43±0.48 15.7±06 186±0.003 F12 0.645±0.003 0.745±0.002 24.3±0.59 12.6±4 155±0.001 Table 6: Pre compression properties of formulations (F13-F24) containing D-manntiol as Diluent Parameters Formulation code Bulk Density(ρ b ) gm/cc Tapped Density(ρ t ) gm/cc Angle Repose(θ) of Carr s index (%) Hausner s ratio F13 0.628±0.004 0.770±0.003 27.4±0.47 18.3±0.03 126±0.004 F14 0.664±0.006 0.780±0.001 26.4±0.43 14.8±0.06 174±0.003 F15 0.676±0.003 0.796±0.004 25.32±0.43 15.0±0.07 177±0.004 F16 0.691±0.003 0.803±0.003 28.85±0.52 13.9±0.03 162±0.004 F17 0.694±0.004 0.779±0.006 24.56±8 10.9±0.02 127±0.005 F18 0.642±0.003 0.754±0.004 25.34±1 14.8±.0.04 174±0.003 F19 0.646±0.004 0.773±0.007 288±3 16.42±0.03 196±0.001 F20 0.617±0.002 0.734±0.004 256±1 15.9±0.01 189±0.001 44

F21 0.636±0.007 0.753±0.001 26.35±03 15.5±0 183±0.003 F22 0.678±0.003 0.763±0.002 28.56±0.51 11±0.02 125±0.001 F23 0.657±0.002 0.758±0.005 27.67±0.4 12.9±0 153±0.004 F24 0.654±0.003 0.768±0.002 28.59±09 14.8±0.01 174±0.001 All the tablets were evaluated for post compression parameters like thickness, hardness, friability, weight variation, drug content, wetting time, in vitro disintegration time and the results were found to be within the pharmacopoeial limits. The results were furnished in tables 7, 8, 9, 10. Table 7: Post -compression properties of formulations (F1-F12) containing DCP as diluent Parameters Formulation code Thickness (mm) Hardness (Kg/cm 2 ) Weight variation (mg) Friability (%) Drug content (%) F1 35±0.03 34±0 200±03 49± 99±0 F2 38±0.03 3.33±05 200±0.51 34±0 99.8±0 F3 35±0.02 3.45±01 200±02 0.450± 99.9±0 F4 35±0.01 3.48±04 199±03 0.514±0 100±0 F5 30±0.03 3.46±04 200±0.04 0.438± 99.7±0 F6 37±0.02 3.48±03 199±00 0.452± 98.9±0 F7 3.33±0.01 3.50±05 200±05 0.513±0 98.9±0 F8 3.35±0.02 3.45±06 200±04 0.532± 99.9±0 F9 35±0.02 3.45±04 200±0.51 0.453± 99.8±0 F10 39±0.01 3.49±05 200±5 0.422±0 99.9±0 F11 32±0.03 3.34±03 200±0.04 0.429±0 99.8±0 F12 33±0.02 3.49±02 199±0.68 0.501± 98.9±0 Table 8: Post -compression properties of formulations (F13-F24) containing D-manntiol as diluent Formulation code Thickness (mm) Hardness (Kg/cm 2 ) Weight variation (mg) Friability (%) Drug content (%) F13 3.99±0.02 3±0.73 200±4 49 ± 99.9±0 F14 3.60±0.03 3.3± 200±04 68 ± 99.8±0 F15 3.9±0.01 3.45±0.45 200±0.54 0.414 ±0 98.9±0 45

F16 3.98±0.01 3.4±0.5 200±2 0.506 ± 100±0 F17 3.54±0.02 3.36±03 199±03 0.464 ±0 99.8± F18 3.55±0.02 3.48±04 200±05 0.432 ± 99.9±0 F19 3.43±0.01 3.36±0 200±04 0.416 ± 99.9±0 F20 35±0.02 3.4 ±0.7 199±04 0.515 ±0 99.9±0 F21 3.94±0.01 3± 200±2 53 ±0 99.9±0 F22 3.95±0.01 3.4± 200±0.5 0.438 ± 99.8±0 F23 3.95±0.02 3.3±0.79 199±0.6 0.514 ± 99.9±0 F24 3.94±0.01 3.4±0.8 200±0.4 0.449 ± 99.9±0.04 Hardness of all the tablets was maintained in the range of 3-3.5kg/cm 2. Thickness of the tablets was between 35-3.99mm. The results of friability test i.e., -0.5% and hardness indicated good mechanical resistance of all tablets. The drug content of almost all formulations was uniform and found to be in the range of 98.9-100%. Table 9: Post compression characteristics of the formulated ODT (F1-F12) containing DCP as diluent Formulation code Wetting Time (sec) Disintegration Time (sec) F1 18.5±1 15.56±2 F2 16.3±2 13.32±1 F3 15.5±1 12.59±1 F4 8.5±1 5.5±1 F5 20.±1 15±2 F6 14±2 8±1 F7 13±1 77±1 F8 10±1 56±2 F9 19±1 15.89±1 F10 14±2 10±1 F11 12±2 8.3±1 F12 10±1 6±2 46

Table 10: Post compression characteristics of the formulated ODT (F13-F24) containing D- manntiol as diluent Formulation code Wetting Time(sec) Disintegration Time(sec) F13 27±1 24±1 F14 23±2 20±2 F15 20±1 17±1 F16 20±1 17±1 F17 15±1 10.9±1 F18 15±1 10.7±1 F19 15±1 10.4±2 F20 15±2 10±1 F21 34.4±1 30±2 F22 33±2 30±1 F23 29.8±1 26±1 F24 21±1 18±1 All the formulations showed less in vitro disintegration time <30 sec, these results satisfy the definition of ODT by USP&EP. Formulations containing mannitol took more time for wetting and in vitro disintegration compared to those containing DCP. The values of low wetting time indicate that these formulations disperse fastly when kept in the mouth. IN VITRO DISSOLUTION STUDIES: The in vitro dissolution studies were carried out and the results were furnished in table 11, 12 and shown in figures 4, 5, 6, 7, 8, 9. The drug release patterns of all tablets revealed that on increase in concentration of superdisintegrant the drug release also increased. The tablet prepared from tapioca starch (7.5%) as superdisintegrant, DCP as diluent showed drug release of 100% within 5min whereas formulations with 2.5%, 5%, 10% took 10min for maximum percent drug release. The tablets prepared using crospovidone, SSG in different strengths like 2.5%, 5%, 7.5%, 10% respectively with DCP as diluent showed maximum percent drug release in more than 5min. The tablets prepared from tapioca starch(2.5%, 5%), as superdisintegrant and D-mannitol as diluent took more than 10min for maximum percent drug release. The tablets prepared from tapioca starch(7.5%), as superdisintegrants and D-mannitol as diluent gave drug release of 98.5% in 10min. The drug release patterns of formulations with crospovidone as superdisintegrant and D-mannitol as diluent are almost similar i.e., maximum percent drug release in 10min. The formulation with SSG(10%) and D-mannitol took 10min for drug release 47

whereas other ratios took more than 10min for maximum percent drug release. Therefore among all formulation F3 containing 7.5% tapioca starch as superdisintegrant and DCP as diluent showed rapid disintegration, better drug release of 100% within 5min. Table 11: Cumulative percent drug release of Paroxetine HCL in formulations containing DCP as diluent Tim Cumulative percent drug release with MSD e (mi n) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12 0 0 0 0 0 0 0 0 0 0 0 0 0 1 13.96±0. 1 20.78±0. 05 55.82±0 47.34± 0 11.93± 20.04±0. 06 27±0. 1 37.93± 0 10.89± 11.93± 0 20.48± 338± 3 16.79±0. 3 28.08±0. 1 92.83±0 66.96± 20.47± 28.08±0. 07 36.61± 51.79± 13.31± 20.47± 25.9±0. 2 65± 0 5 203±0. 3 47.49±0. 2 100±0.0 01 86.62± 47.08± 56.89±0. 08 68.75± 88.01± 153± 36.57± 59.77± 0 82.52± 10 55.93±0. 2 92.78±0. 3 99.08± 0 78.95± 90.8±0.0 6 96.04± 100±0. 2 39.67± 558± 0 71.66± 0 98.69± 0 15 65.54±0. 4 20 77.39±0. 05 98.38±0. 05 100±0.0 1 100±0. 01 87.79± 88.94± 96.89±0. 09 982±0. 05 98.95± 59.53± 71.45± 0 81.39± 0 91.87± 892± 95.04± Table 12: Cumulative percent drug release of Paroxetine HCL in formulations containing D- mannitol as diluent Time Cumulative percent drug release with MSD (min ) F13 F14 F15 F16 F17 F18 F19 F20 F21 F22 F23 F24 0 0 0 0 0 0 0 0 0 0 0 0 0 1 10.45± 0 20.63±0 45.86±0 46±0 45.31±0 45.86±0 455±0 45.39±0 248±0 25.39±0 44.98±0 47.35±0 3 14.92± 5 16.977 ± 10 54.77± 0 15 832± 0 20 99±0.0 6 21.7±0. 1 61.07±0.3 81.77±0 85.95±0.04 86.72±0.06 69.9±0. 2 84.96±0.3 98.51±0 72±0.06 856±0 984±0 69.53±0 89.38±0 94.84±0.06 70.64±0.04 889±0 97.78±0 1 78±0 88.84±0 99.84±0 70.49±0.06 88.73±0 36.95±0 44±0. 2 98±0 78.56±0 933±0 94.69±0 39.54±0.3 73.54±0 84.8±0. 1 91±0 96.32±0 69.02±0 84.81±0 927±0.3 975±0 981±0 70.82±0 88.32±0 97.79±0 48

Cumulative percentage drug release Cumulative percentage drug release Cumulative percentage drug release Research Article CODEN: IJPRNK ISSN: 2277-8713 100 80 60 40 20 0 0 5 10 15 20 25 30 Time(min) F1 F2 F3 F4 Figure 4: Drug release profile of tablets containing tapioca starch as superdisintegrant and DCP as diluent 100 80 60 40 20 0 0 5 10 15 20 25 30 Time(minutes) F5 F6 F7 F8 Figure 5: Drug release profile of tablets containing Crospovidone as superdisintegrant and DCP as diluent 100 90 80 70 60 50 40 30 20 10 0 0 5 10 15 20 25 30 F9 F10 F11 F12 Time(minutes) 49

Cumulative percentage drug release Cumulative percentage drug release Research Article CODEN: IJPRNK ISSN: 2277-8713 Figure 6: Drug release profile of tablets containing sodium starch glycolate as superdisintegrant and DCP as diluent 100 90 80 70 60 50 40 30 20 10 0 0 5 10 15 20 25 30 F1 3 F1 4 Time(minutes) Figure 7: Drug release profile of tablets containing tapioca starch as superdisintegrant and D- mannitol as diluent 100 90 80 70 60 50 40 30 20 10 0 0 5 10 15 20 25 30 F17 F18 F19 F20 Time(minutes) Figure 8: Drug release profile of tablets containing Crospovidone as superdisintegrant and D- mannitol as diluent 50

Cumulative percent drug release Research Article CODEN: IJPRNK ISSN: 2277-8713 100 90 80 70 60 50 40 30 20 10 0 0 5 10 15 20 25 30 Time(minutes) F21 F22 F23 F24 Figure 9: Drug release profile of tablets containing sodium starch glycolate as superdisintegrant and D-mannitol as diluent IN VITRO RELEASE KINETICS: The in vitro drug release data was fitted into different kinetic models like zero order, first order and regression values were furnished in tables 13,14. The results revealed that correlation coefficient values of first order were better compared to zero order for almost all formulations. The first order plots of formulations showed fair linearity, with regression (R 2 ) values between 0.837-0.998. The first order plot of F3 formulation showed fair linearity indicated by regression value R 2 = 0.998. Thus all the formulations were found to follow first order kinetics. Table 13: Different kinetic models of Paroxetine HCl ODT s ( F1-F12) FORMULATION CODE ZERO ORDER FIRST ORDER R 2 R 2 F1 0.920 0.990 F2 0.871 0.968 F3 0.816 0.998 F4 0.664 0.987 51

F5 0.877 0.953 F6 0.915 0.983 F7 0.860 0.983 F8 0.832 0.976 F9 0.965 0.982 F10 0.882 0.965 F11 0.843 0.990 F12 0.834 0.984 Table 14: Different kinetic models of Paroxetine HCl ODT s (F13-F24) FORMULATION CODE ZERO ORDER FIRST ORDER R 2 R 2 F13 0.819 0.837 F14 0.686 0.821 F15 0.740 0.992 F16 0.691 0.989 F17 0.424 0.933 F18 0.443 0.993 F19 0.442 0.995 F20 81 0.909 F21 0.788 0.98 F22 0.662 0.971 52

F23 0.447 0.948 F24 0.655 0.981 CONCLUSION: The Paroxetine orodispersible tablets were successfully prepared. The optimized formulation was F3. The proposed method of formulation was found to possess reproducible characteristics in dispersion time and dissolution time. The tapioca starch was successfully used as superdisintegrant. REFERENCES: 1. Makino T, Yamada M. and Kikuta: J. Fast dissolving tablet and its production, 1993;European Patent. 0553777 A2. 2. Orodispersible Tablets, European Pharmacopeia, Version 6.5, 2009. 3. Guidance for Industry on Orally Disintegrating Tablets US Department of Health and human Services, Food and Drug Administration, CDER, December 2008. http://www.fda.gov/cder/guidance/index.htm 4. Potter WZ and Hollister LE: Antidepressant agents Basic & Clinical Pharmacology, 9th edition, New York, USA, B. G. Katzung, Ed., McGraw Hill, 2004. 482-496. 5. Katzman MA:"Current considerations in the treatment of generalized anxiety disorder",(2009); CNS Drugs 23 (2): 103 20. 6. Sweetman SC. Ed., Martindale: The Complete Drug Reference, Pharmaceutical Press, London, UK, 2009; Vol-1 36th edition: p.414. 7. Navarro V. Improving medication compliance in patients with depression: use of orodispersible tablets. 8. Arun raj. R et al: comparative evaluation of potato starch and banana powder as disintegrating agents in aceclofenac tablets formulation. International Journal of Pharmacy and Pharmaceutical Sciences,2013; Vol 5, Issue 2. 9. Nattawat Nattapulwat, Narumol Purkkao, Ornamphai Suwithayapanth: Evaluation of Native and Carboxymethyl Yam (Dioscorea esculenta) Starches as Tablet Disintegrants. Silpakorn University Science and Technology Journal 2008, 2(2), 18-25. 53

10. Mark Albano Avani F. Amin Tejal J.Shah, Reena Dua and Renuka Mishra. Superdisintegrants: An economical alternative. Pharmafocusasia http://www.pharmafocusasia.com/manufacturing/superdisintegrants.htm. 11. Tapioca starch; Quality starch and chemicals (India) Pvt.Ltd. 12. Buffer Solutions, USP 30, NF 25 Asian edition, Rockville, MD: united state pharmacopoeial convention Inc; 2007, 2724. 13. The united state pharmacopoeia, USP 30-NF 25 Asian edition, Rockville, MD: united state pharmacopoeial convention lnc; 2007, 2271-2273. 14. Lachman and Lieberman: The Theory and Practice of Industrial Pharmacy, 3 rd edition; 292-303. 54