Design and In-Vitro Evaluation of Rapidly Disintegrating Tablets of Rizatriptan Benzoate

 

Doddayya Hiremath1*, Prakash Goudanavar1, Shrishail S Patil1, Priyanka Y. Chowgule1,

  S.R. Reddy1 and Kranthi Kumar Sirse2

1Department of Pharmaceutics N.E.T Pharmacy College, Mantralayam Road, Raichur-584103, Karnataka, India

2Department of Pharmaceutics, Karnataka College of Pharmacy, Bidar, Karnataka, India

*Corresponding Author E-mail: shailpharma@gmail.com

 

ABSTRACT:

Rizatriptan benzoate is used in the treatment of migraine and has bitter taste. The taste has to be masked in order to reduce its bitterness to increase its palatability and also to improve patient compliance. In the present study, attempts were undertaken to mask the bitter taste by complexation technique using ion exchange resins. Thus taste masked granules or resinates of Rizatriptan benzoate were formulated into the rapidly disintegrating tablet to achieve quicker onset of action and therefore to combat the migraine attacks in the fastest way. Tablets were prepared by direct compression method using various superdisintegrants like Indion 234, Crosscarmellose sodium (Ac-Di-Sol) and Sodium starch glycolate of about 1 - 4% concentration. Efficient drug loading was obtained by batch process; the loading process was further optimized for resin type, pH of loading solution and drug: resin ratio. The complex was further evaluated for bulk density, angle of repose, drug release and was characterized by infrared spectroscopy and differential scanning calorimetry (DSC). Among all the designed formulations R4, R8 and R12 were found to be promising and displayed an in vitro dispersion time ranging 15 to 20s, which facilitates their faster dispersion. The drug release was, 99.28% from the batch R4, 98.26% from batch R8 and 97.48% from batch R12.

 

KEYWORDS: Rapidly disintegrating tablets, Rizatriptan benzoate, Tulsion 339, complexation, direct compression.

 

INTRODUCTION:

Rapidly disintegrating tablets have started gaining popularity and acceptance as new drug delivery systems, because they are easy to administer and lead to better patient compliance. Usually, elderly people experience difficulty in swallowing the conventional dosage forms such as tablets, capsules, solutions and suspensions because of tremors of extremities and dysphagia. Fast‐disintegrating drug delivery systems may offer a solution for these problems.

 

Recent development in fast disintegrating technology mainly works to improve the disintegration quality of these delicate dosage forms without affecting their integrity1.

 

Migraine is a neurologic disease, associated with throbbing intense headache in one half of the head2. It is characterized by recurrent attacks of intense headache and nausea that occur at irregular intervals and last for several hours.

 

In classic migraine, the attack is typically heralded by an “aura” accompanied by spreading homonymous visual field defects with colored sharp edges. In addition, the patient cannot focus on certain objects, has a ravenous appetite for particular foods, and is hypersensitive to odors (hyperosmia) or light (photophobia). The exact cause of these complaints is unknown; however, a disturbance in cranial blood flow is the likely underlying pathogenetic mechanism. Pharmacotherapy of migraine has two aims: stopping the acute attack and preventing subsequent ones3.

 

Triptans, which are serotonin receptor 5- HT1B/1D agonists, have recently become the gold standard of migraine treatment4.All triptans are selective for cranial arteries (through their activation of 5-HT1B receptors) and are more potent at meningeal vessels than at other vascular beds. Rizatriptan, for example, is 10 times more potent at meningeal arteries than at coronary arteries5.

 

Rizatriptan benzoate, a novel serotonin 5-HT1D:1B receptor agonist for the acute oral treatment reduces the pulsation that may be responsible for the pain of migraine6, having an oral bioavailability of 40-45% 7. In clinical trials, rizatriptan oral doses of 5 and 10mg were found to be efficacious and generally well tolerated in aborting migraine headache8. Rapidly disintegrating drug delivery system are solid dosage form containing medicinal substances that disintegrate within a matter of seconds when placed upon the tongue. Therefore an attempt has been made to develop and characterize its feasibility for rapidly disintegrating tablets.

 

MATERIALS AND METHODS:

Rizatriptan benzoate was obtained as a gift sample from Arbindo pharmaceuticals Ltd, Hyerabad. Tulsion 339 and indion 234 was obtained from Ion exchange India limited, Pune. Cross carmellose sodium and Sodium starch glycolate obtained from S.Zaveri Pharmaken Ltd; Mumbai. Aspartame, Talc, Magnesium stearate, Aerosil was obtained S.D. Fine chemicals Pvt Ltd, Mumbai. All other chemicals/solvents used were of analytical grade.

 

Preparation of Rizatriptan benzoate -Tulsion 339 complexes: 9

Batch method was used to prepare drug-resin complex. Accurately weighed specific quantity of resin was transferred to a 100 ml beaker containing 75 ml of water, stirred for 2 hrs at 100 rpm by using mechanical stirrer, then filtered through whatman filter paper and dried under vacuum up to 24 h. Weighed quantity of resin (100 mg) was placed in a beaker containing 25ml of deionised water and allowed to swell for 60 min. Accurately weighed 100 mg of Rizatriptan benzoate was added to the resin solution and stirred for 6 h. The obtained mixture was filtered through Whatman filter paper No.41 and residue was washed with 75 ml of deionised water. Unbound drug in filtrate was estimated spectrophotometrically at 281 nm against blank and drug-loading efficiency was calculated.

 

Preparation of rapidly disintegrating tablets: 9

Tablets containing Drug-Tulsion 339 complex equivalent to approximately 10 mg of Rizatriptan benzoate were prepared by direct compression method The ingredients were mixed homogenously and co-grounded in a glass mortar and pestle and were passed through sieve No.40. Then, talc and magnesium stearate were added, mixed for 5 min and passed through sieve No.80. Finally these granules were compressed on tablet compression machine using 4 mm standard punches to give tablet weight of 200 mg. The formulation details are given in Table 1.

 

Characterization of rapidly disintegrating tablets:

FTIR Studies:

Pure drug, inclusion complex and optimized formulation (R4) were subjected for FTIR analysis using Fourier transformer infrared spectrophotometer (8600, Shimadzu Corporation, Japan). The samples were prepared on KBr-press (Spectra Lab, India) and scanned over wave number range of 4000 to 400 cm -1. Spectra were analyzed for drug polymer interactions and functional groups.

 

DSC Studies:

The optimized complexes were subjected to differential scanning calorimeter equipped with an intra cooler (NETZSCH, DSC 200PC, Japan). Indium/Zinc standards were used to calibrate the DSC temperature and enthalpy scale. The samples (Pure drug, Drug - Tulsion complex and R4) were sealed in aluminum pans and heated at a constant rate of 100C/ min over a temperature range of 20-2500 C. Inert atmosphere was maintained by purging nitrogen gas at a flow rate of 10 ml/min.

 

Evaluation of rapidly disintegrating tablets

Hardness 10

The tablet hardness, which is the force required to break a tablet in a diametric compression force. The hardness tester used in the study was Monsanto hardness tester, which applies force to the tablet diametrically with the help of an inbuilt spring. It is expressed in Kg / cm2.

 

Friability:11

Friability of the tablets was determined using Roche friability (Electrolab, Mumbai). This device subjects the tablets to the combined effect of abrasions and shock in a plastic chamber revolving at 25 rpm and dropping the tablets at a height of 6 inches in each revolution. Preweighed sample of tablets was placed in the friabilator and were subjected to 100 revolutions. Tablets were dedusted using a soft muslin cloth and reweighed.

The friability (f) is given by the formula.

f = (1- W0 / W) × 100

Where, W0 is weight of the tablets before the test and

W is the weight of the tablet after the test

 

Weight variation test:10

Weight variation test was carried out as per IP. Twenty tablets were randomly selected and individually weighed. The average weight and standard deviation was calculated.

 

In vitro disintegration time: 10

The disintegration time of the tablet was measured in water (37±2°C) according to disintegration test apparatus with disk. The time in seconds taken for the complete disintegration of the tablet with no palpable mass in the apparatus was measured in seconds. Three tablets from each batch (formulation) were tested for the disintegration time calculations.

 

In vitro dispersion time:12

In vitro dispersion time was measured by dropping a tablet in a beaker containing 50 ml of Sorenson’s buffer pH of 6.8 at 37±0.5°C. Time required for complete dispersion of a tablet was measured. Three tablets from each formulation were randomly selected and in vitro dispersion time was performed.

 

Wetting time:13

The wetting time of the tablets can be measured using a simple procedure. Five circular tissue papers of 10 cm diameter are placed in a Petri dish with a 10 cm diameter. Ten millimeters of water containing Eosin, a water soluble dye, is added to Petri dish. 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 a wetting time.

 

 

Table 1: Composition of Rizatriptan benzoate - Tulsion 339 complex (1:1) rapidly disintegrating tablets

Ingredients (mg)

R1

R2

R3

R4

R5

R6

R7

R8

R9

R10

R11

R12

Amount of complex equivalent to 10 mg of drug

20

20

20

20

20

20

20

20

20

20

20

20

Spray Dried Mannitol

170

168

166

164

170

168

166

164

170

168

166

164

Indion 234

2

4

6

8

---

---

---

---

---

---

---

---

CCS

---

---

---

---

2

4

6

8

---

---

---

---

SSG

---

---

---

---

---

---

---

---

2

4

6

8

Aerosil

2

2

2

2

2

2

2

2

2

2

2

2

Talc

2

2

2

2

2

2

2

2

2

2

2

2

Magnesium Stearate

2

2

2

2

2

2

2

2

2

2

2

2

Aspartame

2

2

2

2

2

2

2

2

2

2

2

2

Total

200

200

200

200

200

200

200

200

200

200

200

200

 

Water absorption ratio:13

A piece of tissue paper folded twice was placed in a small Petri dish containing 6 ml of water. A tablet was put on the paper and the time required for complete wetting was measured. The wetted tablet was then weighed. Results are shown in Fig. 2. Water absorption ratio (R) is calculated by using the equation.

R = 10 × Wa – Wb

                    Wb

Where, Wa is the weight of the tablets before the test and

Wb is the weight of the tablet after water absorption.

 

Fig. 1: Effect of concentration of superdisintegrant on disintegration time of different tablets

 

Fig. 2: Comparison of wetting time and water absorption ratio of different tablets

 

 

In vitro dissolution studies:14

In vitro drug release study was carried out in 900ml of 0.1N HCl using eight station USP type II apparatus with paddle speed of 50rpm and temperature at 37±0.5°C.The drug release study was performed in 0.1N HCl to demonstrate the availability of Rizatriptan benzoate in gastric pH. About 5 ml of sample was withdrawn at specified time intervals from the dissolution medium and replaced with equal volume of fresh medium. Samples were filtered through Whattmann filter paper and analyzed using UV spectrophotometer (UV-1700, Shimadzu Corporation, Japan) at 280 nm. Results are shown in Fig. 3 - 6.

 

Fig 3: In-vitro release of Rizatriptan benzoate from rapidly disintegrating tablets containing 1% Indion 234 (R1) CCS (R5) and SSG (R9)

 

Fig 4: In-vitro release of Rizatriptan benzoate from rapidly disintegrating tablets containing 2% Indion 234 (R2) CCS (R6) and SSG (R10)

 

Fig 5: In-vitro release of Rizatriptan benzoate from rapidly disintegrating tablets containing 3% Indion 234 (R3) CCS (R7) and SSG (R11)

 

Fig 6: In-vitro release of Rizatriptan benzoate from rapidly disintegrating tablets containing 4% Indion 234 (R4) CCS (R8) and SSG (R12)

 

Stability studies: 15

The optimized tablet formulations were packed in aluminum foil and were exposed to 40°C ± 2°C / 75% ± 5% RH in humidity control oven as per ICH guidelines118 Q1C: “Stability testing of new dosage forms.” Sampling was done at predetermined time intervals of 0, 30 and 60 days.

 

RESULT AND DISCUSSION:

Concentration of Tulsion 339 resin on drug loading:

The drug loading in various drug: resin concentration was found to be 92.18 ± 0.22, 92.68 ± 0.12, 92.71 ± 0.24 respectively for 1:1, 1:2 and 1:3. The optimum drug loading was observed with 1:1 ratio (drug: resin) and further increase in the resin concentration (1:2 to 1:5) has not significantly increased the drug loading. This could be due to the saturation of the resin, which prevented further drug loading16. Thus the 1:1 ratio was used as optimized ratio. The results are shown in Table 2.

 

 

 

Table 2: Effect of concentration of Tulsion 339 resin on drug loading

SL. No

Drug : Resin ratio

Drug loading* (%)

1

1 : 1

92.18 ± 0.22

2

1 : 2

92.68 ± 0.12

3

1 : 3

92.71 ± 0.24

*Average of 3 observations, ± SD.

 

Mmicromeritic properties:

The method employed for the preparation of rapidly disintegrating tablets in this study was direct compression for which the drug or the mixture of drug and polymer should possess good flow properties. Plain Rizatriptan benzoate exhibited high angle of repose (45.10 ± 0.48) indicating extremely poor flow property which was further supported by high Carr’s index (23.54 ± 0.26) and Hausner’s ratio (1.34 ± 0.82). Hence it was necessary to use directly compressible vehicle like spray-dried mannitol, the use of which not only facilitate improvement in flowability but also impart some sweet taste to the preparation. After the addition of directly compressible vehicle and flow promoters (Aerosil, Talc and Magnesium Stearate), all the formulations exhibited good flow characteristics suitable for direct compression. The results of the micromeritic studies are given Table 3.

 

 

Physico-chemical evaluation of tablets:

As the material was free flowing, tablets were obtained of uniform weight (0.94 – 1.37%) due to uniform die fill with acceptable variation as per IP specification i.e. below 7.5 %. Hardness of the tablets was between 2.8 to 3.3 kg/cm2 for all the formulations. The thickness was ranged from 5.12 to 5.38 mm. Friability was found to be in between 0.42 to 0.66, the value below 1 % was an indication of good mechanical resistance of the tablet. The drug content was found to be 98.32 to 99.82 %, which was within the acceptable limits. The results of the physico-chemical evaluation of the prepared tablets are given in Table 4.

 

The most important parameter that is needed to be optimized during the development of rapidly disintegrating tablets is the disintegrating time. There is a good relation between wetting time and disintegration time. Wetting time which is an important criteria for understanding the capacity of disintegrants that swell in presence of little amount of water.

 

As an effect of swelling of super disintegrant, the wetted surface of the carrier increases, which promotes wettability and dispersibility of the system and there by increases the disintegration and dissolution. The optimum concentration of superdisintegrant can be selected according to critical concentration of disintegrant. Below this concentration the tablet disintegration time is inversely proportional to the concentration of superdisintegrant, where as if concentration of superdisintegrants incorporated in tablet is above the critical concentration, the disintegration time remains approximately constant or even increases (Swamivelmanickam M et al).

 

Table 3: Micrometric properties of powder blend

Code

Bulk density g/cm3

Tapped density  g/cm3

Angle of repose (0)

Carr’s index %

Hausner’s  ratio

R1

0.44 ± 0.22

0.49 ± 0.14

22.05 ± 0.17

9.20 ± 0.42

1.09 ± 0.02

R2

0.47 ± 0.15

0.52 ± 0.12

21.19 ± 0.21

8.60 ±  0.14

1.11 ± 0.02

R3

0.50 ± 0.21

0.54 ± 0.14

20.80 ± 0.23

7.40 ±  0.26

1.08 ± 0.02

R4

0.52 ± 0.15

0.52 ± 0.11

20.38 ± 0.23

8.09 ± 0.21

1.08 ± 0.02

R5

0.48 ± 0.15

0.56 ± 0.14

21.30 ± 0.13

9.47 ±  0.16

1.10 ± 0.02

R6

0.40 ± 0.06

0.47 ± 0.11

23.88 ± 0.77

8.93 ± 0.77

1.12 ± 0.55

R7

0.44 ± 0.04

0.49  ± 0.12

22.13 ± 0.78

9.54 ± 0.98

1.11 ± 0.45

R8

0.55 ± 0.02

0.59  ± 0.21

21.25 ± 0.81

7.88 ± 1.98

1.07 ± 0.43

R9

0.58 ± 0.16

0.62 ± 0.13

20.40 ± 0.45

10.88 ±1.98

1.06 ± 0.31

R10

0.57 ± 0.04

0.63 ± 0.09

21.94 ± 1.35

7.93± 0.98

1.10 ± 0.27

R11

0.55 ± 0.02

0.61 ± 0.18

23.56 ± 0.70

8.86 ± 1.42

1.11 ± 0.57

R12

0.55 ± 0.02

0.62 ± 0.12

21.45 ± 1.15

9.57 ± 1.13

1.12 ± 0.48

Pure Drug

0.41 ± 0.14

0.55 ± 0.14

45.10 ± 0.48

23.54 ± 0.26

1.34 ± 0.82

*All values are expressed as average of 3 determinations, ± SD

 

Table 4: Physico-chemical evaluation of rapidly disintegrating tablets

Code

Hardness+ (kg/cm2)

Friability† (%)

Weight variation* (%)

Thickness** (mm)

R1

3.2 ± 0.33

0.66 ± 0.01

1.08 ± 0.34

5.19 ± 0.03

R2

3.4 ± 0.25

0.50 ± 0.02

1.07 ± 0.19

5.22 ± 0.01

R3

3.1 ± 0.64

0.65 ± 0.01

1.05 ± 0.37

5.23 ± 0.04

R4

3.3 ± 0.30

0.66 ± 0.03

1.37 ± 0.48

5.27 ± 0.06

R5

3.1 ± 0.28

0.48 ± 0.06

0.99 ± 0.65

5.30 ± 0.02

R6

3.3 ± 0.35

0.58 ± 0.01

1.12 ± 0.16

5.38 ± 0.01

R7

2.9 ± 0.40

0.47 ± 0.04

1.16 ± 0.75

5.34 ± 0.03

R8

2.8 ± 0.46

0.58 ± 0.02

0.97 ± 0.35

5.12 ± 0.05

R 9

3.5 ± 0.24

0.42 ± 0.03

0.94 ± 0.29

5.22 ± 0.04

R10

3.1 ± 0.33

0.58 ± 0.01

0.97 ± 0.14

5.23 ± 0.01

R11

3.3 ± 0.55

0.52 ± 0.02

1.10 ± 0.19

5.32 ± 0.01

R12

2.9 ± 0.64

0.64 ± 0.01

1.07 ± 0.37

5.29 ± 0.04

All values are expressed as mean± SD +n=6, †n=10, *n=20, **n=4

 

The disintegration time is short with quick wetting properties at the core of the tablet. It was also observed that, the wetting time decreased with increasing the concentration of Indion 234. The wetting time of formulation R4 was found 16.78 sec. It was observed that, increasing the concentration of Indion 234 resulted in increased water absorption ratio and decreased disintegration time. Wetting time and water absorption ratio was influenced by nature of polymer and superdisintegrant concentration used in the formulation. Water absorption ratio was inversely proportional to the wetting time for polymer complexes of Tulsion 339. The disintegration test of the tablets was conducted in purified water. Study showed that the disintegrating times of the tablets decreased with increase in the concentration of Indion 234. The results are shown in Table 5 and depicted in Fig 1 and 2.

 

FTIR Studies:

The IR spectrum of formulation R4 containing the pure drug and polymer (Tulsion 339) is taken as the representative formulation and characterized. Due to several ingredients present in the formulation and the presence of moisture in the sample sent for the analysis, the peaks of the spectrum are not fully resolved. However the spectrum is good enough to establish the characterization of the formulation.

 

It is clear from the spectrum that the major absorption bands of the pure drug are observed in the spectrum with negligible variation in their positions. These observations clearly indicated that in the formulation R4 too, there is no interaction of the drug with the polymer and other excipients. The results are shown in Fig. 7.

 

Fig. 7: FTIR studies of Pure drug and optimized formulation (R4)

Rizatriptan benzoate

 

Formulation R4

 

Table 5: Physico-chemical evaluation of rapidly disintegrating tablets

Formulation

Code

Drug

Content (%)*

Wetting time

(sec)*

Water absorption

ratio (%)*

Disintegration

time (sec)*

R1

99.15 ± 0.16

24.93 ± 0.12

78.81 ± 1.64

29.14 ± 0.17

R2

99.51 ± 0.10

21.14 ± 0.27

80.13 ± 1.91

26.01 ± 0.13

R3

98.73 ± 0.29

19.93 ± 0.18

83.81 ± 1.86

24.55 ± 0.21

R4

99.82 ± 0.04

16.78 ± 0.31

85.76 ± 1.34

21.16 ± 0.25

R5

99.22 ± 0.09

26.82 ± 0.26

78.83 ± 1.22

34.28 ± 0.12

R6

99.55 ± 0.16

24.93 ± 0.12

80.91 ± 1.64

28.34 ± 0.17

R7

99.71 ± 0.10

20.14 ± 0.27

81.13 ± 1.91

26.01 ± 0.13

R8

99.03 ± 0.29

17.93 ± 0.18

83.81 ± 1.86

25.55 ± 0.21

R9

99.82 ± 0.04

29.78 ± 0.31

74.76 ± 1.34

37.16 ± 0.25

R10

99.22 ± 0.09

25.82 ± 0.26

78.83 ± 1.22

34.28 ± 0.12

R11

99.51 ± 0.20

22.33 ± 0.17

80.16 ± 1.16

30.01 ± 0.43

R12

99.41 ± 0.18

19.64 ± 0.45

81.81 ± 1.43

28.78 ± 0.68

*All values are expressed as average of 3 determinations, ± SD

 

 

DSC studies:

The observations of the nature of the endothermic peaks and their corresponding values indicating the melting points, suggest that the melting point of the drug and its formulation R4 remained similar to that of reported literature melting point range of the drug.

 

FIG. 8: DSC studies Pure drug and optimized formulation (R4)

Rizatriptan benzoate

 

Formulation R4

As there is no change in the nature of the endothermic peaks and their corresponding melting points, we can come to the conclusion that the drug has not changed its identity and characteristic properties when formulations are prepared from it. The values indicate that there is no interaction of the drug with the polymer and various excipients used for the study. Thus like IR spectra DSC thermograms also support the fact that no interaction of the drug with the polymers in the formulations prepared. The results are shown in Fig. 8.

 

In vitro release study:

In vitro release profile obtained at pH 6.8 indicated that perceivable amount of drug will not be released in saliva while approximately 90% of the drug release would be obtained at acidic pH 1.2 of the stomach. Hence in vitro dissolution of Rizatriptan benzoate tablets was studied in 0.1 N HCl17.

 

In vitro release profile of all formulations (R1-R12) in 0.1 N HCl was in between 97-99% at various time intervals. The cumulative percentage of drug release of all formulations is shown in Fig. 3 - 6. The dissolution profiles of tablet were influenced by nature of superdisintegrants present. The best formulations in case of Tulsion complex with various superdisintegrant with respect to drug release were R4 in case of Indion 234 (99.28% in 3 min), R8 for CCS (98.26% in 3.5 min) and R12 for SSG (97.48% in 3.5 min).

 

In vitro release studied showed better release patterns from 4% of indion 234, crosscarmellose sodium and sodium starch glycolate than 1%, 2% and 3% of the above superdisintegrants as shown in figure below. Formulation R4 containing Indion 234 at 4% gives rapid disintegration than that of R8 and R12 containing Croscarmellose sodium and Sodium starch glycolate at 4%. Superdisintegrant level was proportional to release rate and inversely proportional to that of disintegrating time. The results are shown in Fig 3-6.

 

Stability study:

The stability studies were carried out for selected tablets (R4) at 400±2 C, 75 % RH for one month. The rapidly disintegrating tablets were evaluated by their appearance, drug content, disintegration and drug release study. These studies indicated that no significant change in appearance of tablets and disintegration time. There was no significant change in in vitro drug release profiles at the end of one month stability period.  This indicates that tablets are stable at 400±2 C, 75±5% RH.

 

CONCLUSION:

Rizatriptan benzoate has bitter taste hence approach of complexation was successfully used to mask the bitter taste. Indion 234 exhibited quicker disintegration of tablets than compared to those of CCS and SSG. Dissolution of tablets was directly proportional to the superdisintegrant concentration irrespective of polymer complexes and 4 % w/w concentration was found optimal. In vitro release of optimized formulation R4 showed 99% drug release in 3 min’s. Thus, the bitter taste of rizatriptan was effectively taste masked and successfully developed into rapidly disintegrating tablets which could provide rapid onset of action in combating the migraine attacks.

 

ACKNOWLEDGEMENT:

The authors would like to thank the management of N.E.T Pharmacy College, Raichur, India for providing facilities during the research work.

 

REFERENCES:

1.       Shaikh SA, Khirsagara RV, Quazi A. Fast disintegrating tablets: an overview of formulation and technology. International Journal of Pharm Pharma science.  2(3); 2010: 975-1491.

2.       Bhanushali RS, Gathe MM, Gaikwad RV, Bajaj AN, Morde MA. Nanoemulsion based intra delivery of antimigraine drugs for nose to brain targeting. Indian Journal of Pharmaceutical Science. 2010: 707-09.

3.       Lullmann H, Ziegler A, Mohr K, Bieger DL. Color Atlas of Pharmacology. 2nd edition revised and expanded. 2000; 322.

4.       Ravikumar K, Sridhara B, Krishnanb H. Rizatriptan benzoate a drug for the treatment of migraine headache. Acta Cryst 2007; E63: 1958–60.

5.       Jamieson DG. The safety of triptans in the treatment of patients with migraine. American J. Med 2002; 112: 135-140.

6.       Heinz Lüllmann, Albrecht Ziegler, Klaus Mohr, Detlef Bieger. Lüllmann. Color Atlas of Pharmacology. 2nd edition revised and expanded. 2000; 322

7.       R. S. Bhanushali, M. M. Gatne, R. V. Gaikwad, A. N. Bajaj and M. A. Morde. Nanoemulsion based Intranasal Delivery of Antimigraine Drugs for Nose to Brain Targeting. Indian J Pharm Sci. 2009 Nov–Dec; 71(6): 707-09.

8.       Leea Y, Ermlichb SJ, Sterrettc AT, Goldbergb MR et al. Pharmacokinetics and tolerability of intravenous rizatriptan in healthy females. Biopharm Drug Dispos 1998; 19: 577–81.

9.       Rajni B, Nimrata S, Bansal Y and Shailesh S.  Development and characterization of taste masked mouth dissolving tablets of zolpidem tartrate. International Research Journal of Pharmacy 2010; 1(1): 417-427.

10.     Patel B, Patel D, Parmar R, Patel C, Serasiya T, Sanja SD. Development and in vitro evaluation of fast dissolving tablets of glipizide. International Journal Pharm Pharm Science 2009; 1: 145-150.

11.     Modasiya MK, Lala II, Prajapati BG, Patel VM and Shah D.  A design and characterization of fast disintegrating tablets of piroxicam. International Journal of Pharm Tech Research 2009; 1(2): 353-357.

12.     Swamivelmanickam M, Manavalan R and Valliappan K. Mouth dissolving tablets: An overview. International Journal of Pharmaceutical Science and Research 2010; 1(12): 43-55.

13.     Gnanaprakash K, Mallikarjuna rao K, Sekhar KBC, Chetty M, Alagusundaram M and Ramkanth S. Formulation and evaluation of fast dissolving tablets of valdecoxib. International Journal of Pharmaceutical Technology Research 2009; 1(4): 1387-1393.

14.     Birhade ST, Bankar VH, Gaikwad PD, Pawar SP. Preparation and Evaluation of Cyclodextrin Based Binary Systems for Taste Masking. Intnational Journal of Pharmaceutical Science and Drug Research 2010; 2(3): 199-203.

15.     Gandhi SD, Pandya PR, Jani GK, Upadhyay NN, Nagaich U. Formulation development and evaluation of colon targeted tablets of secnidazole for the treatment of amoebiasis.  International Journal of Pharmaceutical Science Review Research 2010; 5(3): 64-71.

16.     Bhise K, Shaikh S, and Divyakumar B. Taste mask, design and evaluation of an oral formulation using ion exchange resin as drug carrier. American Association Pharm Science and Technology 2008; 9(2): 557-562.

17.     Shishu, Bhatti A and Singh T. Preparation of tablets rapidly disintegrating in saliva containing bitter taste-masked granules by compression method. Indian Journal of Pharmaceutical Science 2007; 80-84.

 

 

 

 

Received on 02.05.2011       Modified on 07.06.2011

Accepted on 10.06.2011      © RJPT All right reserved

Research J. Pharm. and Tech. 4(8): August 2011; Page 1227-1233