Int. J. Pharm. Res. Sci.,2013, 01(1),7-15.

ISSN

2348 –0882

Formulation and Development of Rapid Disintegrating Tablet o...
Int. J. Pharm. Res. Sci.,2013, 01(1),7-15.

ISSN

through sieve no. 18. The dried granules
were then blended with colloida...
Int. J. Pharm. Res. Sci.,2013, 01(1),7-15.

ISSN

2348 –0882

RESULT AND DISCUSSION
Drug Identification
By UV spectroscopy...
Int. J. Pharm. Res. Sci.,2013, 01(1),7-15.

ISSN

Table 4: Evaluation of Tablet Prepared by Wet granulation Method:
*Wetti...
Int. J. Pharm. Res. Sci.,2013, 01(1),7-15.

ISSN

2348 –0882

Table 6: Cumulative % Drug Release for Rapid Disintegrating ...
Int. J. Pharm. Res. Sci.,2013, 01(1),7-15.

ISSN

2348 –0882

not hygroscopic and can be used with
moisture sensitive acti...
Int. J. Pharm. Res. Sci.,2013, 01(1),7-15.

ISSN

2348 –0882

For this study F1, F2 & F5 batches of wet
granulation method...
Int. J. Pharm. Res. Sci.,2013, 01(1),7-15.

ISSN

2348 –0882

matter of seconds and almost all the drug
will be released i...
Int. J. Pharm. Res. Sci.,2013, 01(1),7-15.

8)

9)

ISSN

states Pharmacopial Convection Inc.
Rockville, pg no. 2135
Khali...
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Formulation and Development of Rapid Disintegrating Tablet of Fluoxetine Hydrochloride

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ABSTRACT
Aim: The aim of present work was to
formulate rapid disintegrating tablet of
Fluoxetine HCLwith pleasant taste and
better mouth feel by sublimation technique.
Materials and Methods: The fast
disintegrating tablet is formulated by
sublimation technique. The super
disintegrant used in present formulation was
crospovidone the other excipient used was
mannitol, Ammonium bicarbonate and
camphor. Result and Discussion: The
cumulative % of drug release of F7 batch of
wet granulation method was found to be
99.26% at the end of 4 min. Formulation F7
prepared by direct compression method
showed 99.71 % drug release at the end of 1
min while formulation F7 prepared by wet

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Formulation and Development of Rapid Disintegrating Tablet of Fluoxetine Hydrochloride

  1. 1. Int. J. Pharm. Res. Sci.,2013, 01(1),7-15. ISSN 2348 –0882 Formulation and Development of Rapid Disintegrating Tablet of Fluoxetine Hydrochloride Nikude AS*, Institute of Pharmaceutical Education and Research, Wardha, Maharashtra, India. =================================================================== granulation method 99.26 % drug was ABSTRACT Aim: The aim of present work was to released at the end of 4 min. Dissolution formulate rapid disintegrating tablet of study of optimized batch of tablets F7 Fluoxetine HCLwith pleasant taste and prepared by wet granulation method better mouth feel by sublimation technique. containing 20% ammonium bicarbonate Materials and Methods: The fast revealed most rapid release of drug, t90 for disintegrating tablet is formulated by batch F7 is less than 180 sec. Conclusion : sublimation technique. The super Overall, from the present research work it disintegrant used in present formulation was can be concluded that by using the crospovidone the other excipient used was combination of 10% crospovidone as a mannitol, Ammonium bicarbonate and superdisintegrant and 20% Ammonium camphor. Result and Discussion: The bicarbonate (AB) as a subliming agent by cumulative % of drug release of F7 batch of wet granulation method, a well palatable, wet granulation method was found to be patient-friendly rapid disintegrating tablet 99.26% at the end of 4 min. Formulation F7 could be successfully prepared. The prepared by direct compression method prepared tablet showed sufficient strength showed 99.71 % drug release at the end of 1 coupled with rapid disintegration as well as min while formulation F7 prepared by wet rapid dissolution. Introduction Fluoxetine Hydrochloride1-4 It is N-methyl-3-phenyl-3-[4(trifluoromethyl)phenoxy]propan-1-Amine Hydrochlorid having molecular formula C17H18F3NO.HCl. It belong to category selective serotonin reuptake inhibitor, antidepressant. The MDT was prepared by sublimation technique. Fig1. Fluoxetine Hydrochloride ============================= Formulation of Rapid Disintegrating Tablet All the ingredients were weighed. Then they were mixed together and specified volume of alcoholic solution of PVP (10%) was added and mixed to form coherent mass. The wet mass was granulated using sieve no. 10 and dried for 30 min then Screened Corresponding Author: Nikude AS Email id: ashishnikude5@gmail.com Institute of Pharmaceutical Education and Research, Wardha, Maharashtra, India Received: 07.11.2013 Revised: 08.12.2013 Accepted: 10.12.2013 7
  2. 2. Int. J. Pharm. Res. Sci.,2013, 01(1),7-15. ISSN through sieve no. 18. The dried granules were then blended with colloidal silicon dioxide, talc & magnesium stearate and compressed into tablet using 8 mm flat- 2348 –0882 faced punch on single tablet punching machine. Formulations of Fluoxetine HCl Rapid disintegrating tablet by wet granulation method are shown in Table 1. Table no 1: Formulation of rapid disintegrating tablet by wet granulation method. Compositions for Rapid Disintegrating Tablet of Fluoxetine Hydrochloride by Sublimation Ingredients (Mg) F1 F2 F3 Drug 10 10 Camphor 20 Ammonium Bicarbonate Crospovidone 20 20 Sodium Saccharin 1 1 Colloidal Silicon Dioxide 2 2 Magnesium Stearate 2 2 Talc 4 4 Mannitol q.s. q.s. Total 200 200 Technique (Direct Compression) All the ingredients were weighed. Then they were mixed and compressed into tablet using 8 mm flat-faced punch on single tablet F4 F5 F6 F7 10 10 10 10 10 30 40 20 30 40 20 20 20 20 20 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 4 4 4 4 4 q.s. q.s. q.s. q.s. q.s. 200 200 200 200 200 punching machine. Formulations of Fluoxetine Hydrochloride Rapid disintegrating tablet by direct compression method are shown in Table 2. Table no 2: Formulation of rapid disintegrating tablet by direct compression method. Ingredients (Mg) Drug Camphor Ammonium Bicarbonate Crospovidone Sodium Saccharin Colloidal Silicon Dioxide Magnesium Stearate Talc Mannitol Total F1 F2 F3 F4 F5 F6 F7 10 - 10 20 10 30 10 40 10 - 10 - 10 - - - - - 20 30 40 20 20 20 20 20 20 20 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 4 q.s. 200 4 q.s. 200 4 q.s. 200 4 q.s. 200 4 q.s. 200 4 q.s. 200 4 q.s. 200 8
  3. 3. Int. J. Pharm. Res. Sci.,2013, 01(1),7-15. ISSN 2348 –0882 RESULT AND DISCUSSION Drug Identification By UV spectroscopy Fig: 2 Reported UV scanning of Fluoxetine HCl in Clarke’s analysis of drug and poison By Infrared Absorption Spectrophotometry Fig3: Reported FTIR of Fluoxetine HCl in Clarke’s analysis of drug and Poison 90 %T 75 60 45 30 15 0 400 0 375 0 fluo xetine 350 0 325 0 300 0 275 0 250 0 225 0 200 0 175 0 150 0 125 0 100 0 75 0 50 0 1/cm Fig 4: FTIR Spectrum of Fluoxetine HCl Table no 3: Evaluation of Tablet Prepared by Direct compression Method: *Wetting *Disintegration *% Drug *Hardness *(%) Water Sr. *(%) time time(sec.) ±SD Formulation content absorption (kg/cm2) No. Friability±SD (Sec) ±SD ±SD ratio±SD ±SD 1 F1 97.26±0.63 2.8±0.02 1.2±0.78 122±0.34 71.72±0.5 9 88±1.47 2 F2 98.34 ±0.57 1.2±0.12 2.3±0.73 42±0.42 89.05±0.7 0 30±0.58 3 F3 99.95 ±1.12 0.8±0.04 3.06±0.59 39±0.25 90.41±0.3 6 16±1,39 4 F4 99.97 ±1.99 0.7±0.03 3.8±0.64 8±0.13 97.75±0.4 0 13±0.42 5 F5 97.38 ±0.25 0.9±0.05 3.7±0.72 30±0.34 88.34±0.3 1 12±1.55 6 F6 97.42 ±0.16 0.6±0.01 4.7±0.33 21±0.28 94.29±0.5 9 09±1.15 7 F7 98.75 ±1.07 0.6±0.02 5.2±0.39 16±0.39 95.01±0.6 2 07±0.23 *Each value represents the mean (n=3) ± standard deviation 9
  4. 4. Int. J. Pharm. Res. Sci.,2013, 01(1),7-15. ISSN Table 4: Evaluation of Tablet Prepared by Wet granulation Method: *Wetting *Hardness time *(%) Water Sr. Formula *% Drug (kg/cm2) *(%) (Sec) absorption No. tion content ±SD ±SD Friability±SD ±SD ratio±SD 1 F1 100.75±0.85 4.2±0.1 0.20±0.04 231±0.54 53.38±0.53 2 F2 100.33±1.27 3.5±0.057 0.2±0.07 124±0.24 68.27±0.24 3 F3 101.58±1.52 3.6±0.057 0.4±0.06 94±0.65 70.43±0.36 4 F4 101.99±0.61 2.3±0.08 1.1±0.02 74±0.32 75.18±0.42 5 F5 98.93 ±1.12 3.9±0.02 0.28±0.04 102±0.45 69.25±0.28 6 F6 99.91 ±1.99 3.8±0.02 0.3±0.05 79±0.87 69.33±0.46 7 F7 98.65 ±0.57 3.4±0.03 0.5±0.08 71±0.35 72.38±0.92 *Each value represents the mean (n=3) ± standard deviation 2348 –0882 *Disinteg ration time(sec.) ±SD 244±0.35 97±0.09 87±0.07 64±0.31 65±0.24 49±0.15 37±0.13 Table 5: Cumulative % Drug Release for Rapid Disintegrating Tablet at Different Time Interval with Direct Compression Method in SGF pH 1.2. Sr. Time F1 F2 F3 F4 F5 F6 F7 No. (min) 1 0 0 0 0 0 0 0 0 44.7± 60.57± 2 1 100.1±1.44 100.5±1.66 70.65±0.83 94.95±1.89 99.72±1.32 1.27 0.87 52.0± 73.59± 3 2 94.89±0.57 1.49 0.98 64.5± 97.91± 4 3 1.82 1.21 73.3± 5 4 0.86 94.98± 6 5 0.78 Each value represents the mean (n=3) ± standard deviation 10
  5. 5. Int. J. Pharm. Res. Sci.,2013, 01(1),7-15. ISSN 2348 –0882 Table 6: Cumulative % Drug Release for Rapid Disintegrating Tablet at Different Time Interval with Wet Granulation Method in SGF pH 1.2. Sr.N o. Time (min) F1 F2 F3 F4 F5 F6 F7 1 0 0 0 0 0 0 0 0 2 1 0 13.95±2.49 47.88±0.97 47.88±1.83 51.84±1.79 49.50±1.53 66.15±1.34 3 2 29.34±1.62 23.83±2.09 68.48±0.07 66.14±1.54 56.35±1.37 52.92±1.86 79.74±0.61 4 3 56.77±1.34 31.70±1.71 71.02±1.32 90.09±0.89 60.62±1.68 65.63±1.62 97.64±0.071 5 4 77.96±1.89 48.80±2.09 73.21±1.46 101.5±0.06 72.93±1.54 72.38±0.71. 99.26±0.063 6 5 89.55±0.91 56.18±1.53 77.90±2.01 80.44±1.79 98.97±0.93 7 6 91.85±0.63 71.34±1.82 86.20±0.49 96.99±0.82 102.66±0.68. 8 7 96.85±1.34 74.07±0.79 101.80±0.032 97.52±0.091 9 8 98.19±1.53 75.82±0.69 10 9 98.72±0.64 92.34±0.43 11 10 100.0±0.73 100.3±0.082 12 11 100.8±0.09 101.02±0.07 Each value represents the mean (n=3) ± standard deviation % Cumulative Drug Release 120 F1 F2 F3 80 F4 F5 F6 F7 40 20 0 0 2 4 6 8 10 12 14 Ti me (mi n) % Cumulative Drug Release Figure 4: Dissolution Profile of Rapid Disintegrating Tablet of Batches F1 to F7 Prepared by Direct Compression Method. 120 F1 F2 F3 80 F4 F5 F6 F7 40 20 0 0 2 4 6 8 10 12 14 Ti me(mi n) Figure 5: Dissolution Profile of Rapid Disintegrating Tablet of Batches F1 to F7 Prepared by Wet Granulation Method. 11
  6. 6. Int. J. Pharm. Res. Sci.,2013, 01(1),7-15. ISSN 2348 –0882 not hygroscopic and can be used with moisture sensitive active ingredient. It was used as diluents for its pleasant taste and better mouth feel by virtue of its negative heat of dissolution.5-7 Evaluation of Rapid Disintegrating Tablet of Fluoxetine HCl The rapid disintegrating tablets from batches F1 to F7 of both the methods i.e. direct compression and wet granulation were evaluated for tablet properties such as hardness, friability, wetting time, water absorption ratio, weight variation and disintegration time. In Direct compression method, the batches from F2 to F7 are more friable. Friability of these batches does not comply with USP or any other official standards. Effect of subliming agent type The presence of highly porous structure in the tablet matrix is the key factor for rapid disintegration of rapid disintegrating tablets. The conventional tablet did not disintegrate rapidly because of low porosity. To improve the porosity, volatile substances such as camphor and ammonium bicarbonate (AB) can be used in tableting process, which sublimates from the formed tablets. The effect of subliming agent type was studied by preparing F2 and F5 batch containing camphor and AB, respectively as a subliming agents. The tablet containing camphor showed very less hardness, friability and short disintegration time as compared to tablets containing ammonium bicarbonate. It was observed that the tablets containing camphor did not exhibit complete removal of camphor irrespective of the sublimation time and this is felt by the stinging effect in the mouth1. Also, disintegration time of F5 batch is less than that of F2 batch because of its highly porous structure in the tablet matrix. Thus AB is better as compared to camphor. Effect of method of tablet preparation DISCUSSION AND CONCLUSION Preformulation study On the basis of characterization of the drug, it was concluded that the received drug sample from Cadila Pharmaceuticals Ltd. Ankaleshwar (Gujrat) India. Complies with the compendial specifications for identification and other tests and was suitable for preparation of rapid disintegrating tablet. Drug – Excipient Interaction Study FTIR of the drug confirmed the presences of all prominent peaks are at wave numbers 2986, 2712,1614,1329,1257 and 1122 cm-1 indicating its authenticity. Physical mixture of drug and excipient was characterized by FTIR analysis for any physical as well chemical alteration of the drug characteristics. FTIR spectrum shows prominent bands at 3200.83 cm-1 (sec. NH Stretching), 3032.85 cm-1 (aromatic CH stretching), 2889.17 and 2865.06 cm -1 (aromatic and symmetric aliphatic stretching), 1306.68 cm-1 (C-O-C stretching of ether) , 1615.27 cm-1 (C=C stretching ) and 1740.89 cm-1 (C=O Stretching of ester). From results, it was concluded that there was no interference in the functional group as the principal peaks of the Fluoxetine hydrochloride were found to be unaltered in the drug excipient physical mixture. The physical parameters of drug as well as excipients concluded that these were considerably good to formulate the tablet using sublimation technique. Formulation of Rapid Disintegrating Tablet Polyplasdone XL-10 which is known as crosspovidone (CP) was present in an amount of 10% used as a Superdisintegrants. The disintegrating action of CP was owing to its high capillary activity and rapid swelling in all direction in presence of any physiological fluid. This leads to the rapid development of high internal stresses, which causes the tablet to disintegrate. Mannitol is 12
  7. 7. Int. J. Pharm. Res. Sci.,2013, 01(1),7-15. ISSN 2348 –0882 For this study F1, F2 & F5 batches of wet granulation method were used to assess the importance of subliming agent for the formation of pores into tablet matrix, which helps in rapid disintegration. F2 & F5 batch shows improved disintegration time as compared to F1 batch (244 sec) which is kept as control batch (without subliming agent). Tablets with lower friability (≤ 0.5%) may not break during handling on machines and or shipping. The use of subliming agent resulted in increased friability probably due to increased porosity10-11 Disintegration Time and Friability of Tablets Disintegrating time is very crucial property of rapid disintegrating tablet. It is essential to determine exact disintegrating time of rapid disintegrating tablet. Hence in the present study disintegrating time is evaluated by in vitro and in vivo disintegration test method. It was observed that when crospovidone was used in concentration of 10%, the disintegrating time was found to be 88 sec. & 244 sec. in F1 batch of direct compression & wet granulation method respectively. The result shown in table 6 & 7 indicate that concentration-dependent disintegration was observed in batches prepared using camphor & ammonium bicarbonate as a subliming agent. The porous structure is responsible for faster water uptake; hence it facilitates wicking action of crospovidone in bringing about faster disintegration. It is worthwhile to note that as the concentration of camphor & ammonium bicarbonate increased, the wetting time & disintegrating time is decreased in both the methods i.e. direct compression & wet granulation. Tablets with lower friability (≤ 0.5%) may not break during handling on machines and/or shipping. The use of subliming agent resulted in increased friability probably due to increased porosity36. Batches from F2 to The method of tablet preparation plays an important role in the physical properties of the prepared tablets; all the batches of both the method (direct compression & wet granulation) were used to investigate this effect on the preparation of rapid disintegrating tablet of Fluoxetine HCl. The final blend in direct compression method F4, F6 and F7 have very poor flowability, while granules prepared by wet granulation method exhibites good flowability. In addition, F2 to F7 batches of direct compression method have not acceptable hardness, friability This is because of higher porosity of the tablets which loses the internal strength of tablets and tablets become more friable, while in case of wet granulation method, PVP restore its binding property with other excipients after sublimation process36, 66.The result suggests that the wet granulation method is preferable to the direct compression for preparation of rapid disintegrating tablets of Fluoxetine HCl. Effect of subliming agent concentration Formulae F2 to F7 of wet granulation method were used to study the effect of concentration of subliming agent (Camphor & Ammonium bicarbonate) on properties of rapid disintegrating tablet. The results in the table indicate that the wetting time decreases with increase in concentration of camphor & ammonium bicarbonate, which may be attributed to the increase in water uptake rate by the porous structure formed after sublimation. Due to formation of pores into tablet matrix, more physiological fluids is available to the amorphous open structure of the particles of crospovidone which results in rapid swelling in all direction of particles. This leads to rapid development of high internal stresses which causes the tablet to disintegrate rapidly. When higher percentage of subliming agent is used, more porous and consequently more mechanically weak tablets are produced8-9 Effect of presence of subliming agent 13
  8. 8. Int. J. Pharm. Res. Sci.,2013, 01(1),7-15. ISSN 2348 –0882 matter of seconds and almost all the drug will be released instantaneously. The in vitro dissolution profile in fig. 15 and fig. 16 indicated faster and maximum drug release from formulation F7 in comparison with all batches of both the methods. Formulation F7 prepared by direct compression method showed 99.71 % drug release at the end of 1 min while formulation F7 prepared by wet granulation method 99.26 % drug was released at the end of 4 min. The rapid drug dissolution might be due to easy breakdown of particles due to porous structure formation into the tablet matrix after sublimation of ammonium bicarbonate. Dissolution study of optimized batch of tablets F7 prepared by wet granulation method containing 20% ammonium bicarbonate revealed most rapid release of drug, t90 for batch F7 is less than 180 sec. References 1) www.Drugbank.com. [Accessed on 7Feb.2010] 2) Martindale. The complete drug reference: London; RPS publishing. Edi 35th 2007: vol.1; 351-359. 3) Moini J. Drug therapy for the nervous system: antipsychotic and anti depressant drug; Fundamental ST Pharmacology; 1 ed.Melbourne: Cengage learning; 2010: p.70-71. 4) Moffat, Osselton MD, Widdop B. Clark’s analysis of drugs and poisons. (Edis.) 3rd Edi; Vol. 2. 5) Rowe CR, Sheskey PJ, Weller PJ. Lactose, In: Handbook of Pharmaceutical Excipients, 4th edi, Pharmaceutical Press, London. U.K. 2003. 6) http://www.wikipedia/camphor.Acces sed 05/12/2009. [Last Acessed on 12 Jan 2010] 7) United State Pharmacopeias 24 / NF 19, (2000) Asian Edition, The official compendia of Standards, United F7 of wet granulation method showed good mechanical integrity as compared to same batches of direct compression, but the disintegrating time was a little longer than the arbitrarily chosen value of less than 50 sec. only F7 batch of wet granulation method & F2 to F7 batch of direct compression showed better result in case of disintegrating time i.e. less than 50 sec.Moreover, a good correlation (R2c = 0.9067 & R2a = 0.9643) between the concentration of subliming agent (Camphor & Ammonium bicarbonate) & friability is observed respectively. Because when a higher percentage of subliming agent is used, more porous & consequently more mechanically weak tablets are produced36. Similarly, good correlation (R2c = 0.9508 & R2a = 0.9932) between the concentration of subliming agent (camphor & AB) and disintegrating time is observed which is shown in table 14 & 15 and fig. 19 & 20. These high values of correlation coefficient for percentage friability and disintegrating time indicate a good fit. The correlation coefficient values between in vivo and in vitro disintegration time of the tablet prepared by direct compression and wet granulation are 0.977 and 0.986 respectively. In Vitro Dissolution Studies For all oral solid dosage forms, dissolution study serves as a control test. The same is true for rapid disintegrating tablets. This is because batch to batch consistency can be assured, and dissolution data of the tablets are frequently predictive of the bioavailability of the product. The cumulative % of drug release of F7 batch of wet granulation method was found to be 99.26% at the end of 4 min. As the concentration of subliming agent increases, the time for drug release decreases because at the higher concentration of subliming agent, more porous tablets was formed which easily get disintegrated within the 14
  9. 9. Int. J. Pharm. Res. Sci.,2013, 01(1),7-15. 8) 9) ISSN states Pharmacopial Convection Inc. Rockville, pg no. 2135 Khalid KA, Ahmed AH, Mowafaq MG, Alaa A. Formulation and optimization of orodispersible tablet of Diazepam. AAPS Pharm.Sci.Tech. 2010; 2(1):356-61.doi: 10.1208/s12249-010-9387-y. Gohel M, Patel M, Amin A, Agrawal R, Dave R, Bariya N. Formulation Design and optimization of Nimsulide Using Vacuum Drying Technique. AAPS Pharm.Sci.Tech. 2004, 5(36): 10) 11) 15 2348 –0882 1-6. Gohel M, Patel M, Amin A, Agrawal R, Dave R, Bariya N. Formulation Design and optimization of Nimsulide Using Vacuum Drying Technique. AAPS Pharm.Sci.Tech. 2004, 5(36): 1-6. Shashaku K. Fast disintegrating solid formulations of anirectom. Jpn Kokai Tokyo Koho. 1999; Japanese patent 11 13 662.

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