Int J Curr Pharm Res, Vol 9, Issue 2, 59-63Original Article


FORMULATION AND EVALUATION OF FAST DISSOLVING FILMS OF ELETRIPTAN HYDROBROMIDE

K. PALLAVI, T. PALLAVI

G. Pulla Reddy College of Pharmacy, Osmania University
Email: pallavi.trivedi44@gmail.com

Received: 27 Nov 2016, Revised and Accepted: 23 Jan 2017

ABSTRACT

Objective: The main aim of the present research was to develop an oral fast dissolving polymeric film (FDF) with good mechanical properties, faster disintegration and dissolution when placed on the tongue.

Methods: Eletriptan hydrobromide is prescribed for the treatment of mild to a moderate migraine. The polymers selected for preparing films were Pullulan, Maltodextrin (MDX), Acacia, Sodium alginate (SA), Locust bean gum (LBG), Guar gum (GG), Xanthan gum (XG), Polyvinyl alcohol (PVA), Polyvinyl pyrrolidine (PVP), Hydroxyl propyl methyl cellulose (HPMC) E5, and HPMC E15. Twelve sets of films FN1–FN12 were prepared by solvent casting method with Pullulan and combination of Acacia, MDX, SA, LBG, GG, XG, PVA, PVP, HPMC E5 and HPMC E15. Five sets of films FS1–FS5 were prepared using synthetic polymers like PVA, PVP, HPMC E5 and HPMC E15.

Results: From all the prepared polymer formulations, FN2, FN8, and FS3 were selected based on disintegration time, and drug release and amongst this three FN2 was optimised based on its disintegration time (D. T). The percent drug release of the optimised film was compared with the percent release of the pure drug.

Conclusion: The optimised formulation had a D. T of 16 s and a percent drug release of 97.5% in 10 min in pH 6.8 phosphate buffer and 100.6% drug release in 10 min in 0.1N HCl.

Keywords: oral FDFs, Pediatric, Geriatric, Dysphasia

© 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
DOI: http://dx.doi.org/10.22159/ijcpr.2017v9i2.17386

INTRODUCTION

The oral route is one of the oldest routes which is used for conventional and novel drug delivery. The main reason for this route being the highly preferred is ease of administration. FDFs, a new drug delivery system for the oral delivery of the drugs, was developed in late 1970’s based on the technology of the transdermal patch. These were developed as an alternative to tablets, capsules, and syrups for pediatric and geriatric patients who experience difficulties in swallowing traditional oral solid-dosage forms [1]. By definition, “a solid dosage form that dissolves or disintegrates quickly in the oral cavity, resulting in solution or suspension without the need for administration of water is known as an oral fast-dispersing dosage form”[2].

The novel technologies of oral fast-dispersing dosage forms are also known as fast dissolve, rapid dissolve, rapid melt and quick disintegrating systems. However, the function and concept of all these dosage forms are similar. These fast dissolving systems are used in the condition called Dysphasia (difficulty in swallowing), this is common among all age groups but especially in geriatric and pediatric patients [3].

Special features of FDFs [4, 5]

Advantages of oral FDFs [6-9]

Disadvantages of oral FDFs [10, 11]

MATERIALS AND METHODS

Eletriptan hydrobromide was used as an active ingredient, acacia, maltodextrin, sodium alginate, locust bean gum, xanthan gum, guar gum, HPMC E5, E15, PVA, PVP were used as water soluble polymers. Mannitol used as a sweetening agent and propylene glycol as a plasticizer. All polymers, propylene glycol, Mannitol and Glycerol, were procured from SD Fine chemicals Ltd. All other chemicals used were of analytical grade.

Formulation of FDFs

The general methods used to prepare FDFs are semisolid casting, solvent casting, hot melt extrusion, solid dispersion and rolling. In the present study, the FDF’s were prepared using solvent casting method [10]. The casting solution was prepared by mixing polymer solution with drug, plasticizer, sweetener and flavor. The resulting solution was deaerated by sonication, then poured into appropriate moulds and dried to obtain the films. The final dosage form was cut into strips (2×2 cm) which contained the required amount of drug (20 mg). Different formulations were prepared by varying the polymers and plasticizer concentrations (table 1 and 2). The prepared films were then evaluated for thickness, folding endurance, weight variation, disintegration time, dissolution time and drug content.

Evaluation of films

Standard curve of eletriptan hydrobromide

The standard curve of EHBR was obtained in two different mediums 6.8 pH phosphate buffer and 0.1N HCl. 100 mg of EHBR was dissolved in 10 ml of 6.8 pH phosphate buffer and another 100 mg of drug was dissolved in 0.1N HCl, then the volume was made up to 100 ml with respective mediums. 10 ml of the above solutions were diluted up to 100 ml with buffer and 0.1N HCl respectively. From this solution, 1 ml was taken, and volume was made up to 100 ml (1 μg/ml). Then by serial dilution, solutions with concentrations 2 μg/ml, 4 μg/ml, 6 μg/ml, 8 μg/ml, 10 μg/ml, 12 μg/ml, 14 μg/ml and 16 μg/ml were prepared. Absorbance was measured on a Shimadzu Double Beam Spectrophotometer (UV1601) at 222.0 nm (table 3, 4).

Table 1: Composition of different films made of natural polymers

Ingredients FN1 FN2 FN3 FN4 FN5 FN6 FN7 FN8 FN9 FN 10 FN 11 FN 12
EHBR 140 140 140 140 140 140 140 140 140 140 140 140
PULLULAN* 2 2 2 2 2 2 2 2 2 2 2 2
ACACIA* 0.5 - - - - - 1 - - - - -
MALTO-DEXTRIN* - 1 - - - - - 2 - - -
LOCUST BEANGUM* - - 0.5 - - - - - 1 - - -
SODIUM ALGINATE* - - - 0.5 - - - - - 1 - -
GUAR GUM* - - - - .25 - - - - - .50 -
XANTHAN GUM* - - - - 0.5 - - - - - .75
MANNITOL* 20 20 20 20 20 20 20 20 20 20 20 20
PROPYLENEGLYCOL** 10 10 10 10 10 10 10 10 10 10 10 10
WATER 10 10 10 10 10 10 10 10 10 10 10 10

NOTE: All the ingredients were dissolved in 10 ml distilled water, EHBR-Eletriptan hydrobromide in mg; FN-Formulations with natural polymers, *are in %w/v; **is in % w/w of the polymer.


Table 2: Preparation of oral films using combination of various synthetic polymers

Ingredients FS1 FS2 FS3 FS4 FS5
EHBR 140 140 140 140 140
PVA* 3 1.75 - - -
PVP* 2 - - - 2
HPMC E5* - 1.75 3 1 3
HPMC E15* - - - 2 -
Mannitol* 0.2 0.2 0.2 0.2 0.2
Propylene glycol** - 0.2 0.5 - 0.2
PEG 400* 0.2 - - 0.3 -
Water 10 10 10 10 10

*-are in %w/v; ** is in % w/w of polymer.


Table 3: Standard graph of EHBR in pH 6.8 Phosphate buffer

Concn (ug/ml) Absorbance (mean±SD)
0 0
2 0.178±0.0027
4 0.348±0.015
6 0.503±0.013
8 0.684±0.027
10 0.829±0.036
12 0.981±0.024
14 1.144±0.0051

n=6


Drug-excipients compatibility study by FT-IR

EHBR compatibility with excipients was studied by FT-IR spectroscopy. From the spectra of the EHBR, it was observed that the main functional groups of the molecule were aromatic phenyl with sulfone and amide. The most intensive peak was observed at 1140 cm-1 which were due to C-N bending in the structure of EHBR. Another sharp peak was seen at 1640 cm-1 which indicated the presence of C=C (phenyl group), peak at 1305 cm-1 was due to sulfone moiety. A peak at 3245 cm-1 indicated the presence of N-H stretch, N-H bending was seen at 1480 cm-1, and a peak at 528 cm-1 was due to the presence of bromide group as seen in fig. 3.

From the FTIR spectra as seen in fig 4, it is very clear that the drug is compatible with pullulan and Maltodextrin as all the characteristic peaks of drug were retained. Hence there is no incompatibility between the drug and these excipients.

Fig. 1: Standard graph of EHBR in pH 6.8 phosphate buffer


Table 4: Standard graph of EHBR in 0.1N HCl

Concn (ug/ml) Absorbance (mean±SD)
0 0
2 0.210±0.0061
4 0.357±0.0092
6 0.512±0.0115
8 0.652±0.0030
10 0.828±0.0035
12 0.98±0.001
14 1.15±0.002

n=6


Fig. 2: Standard graph of EHBR in 0.1N HCl


Fig. 3: FTIR spectrum of pure drug


Fig. 4: FTIR spectrum of EHBR, pullulan and maltodextrin

Weight variation of the film

The casted film was cut into various 2x2 cm films from different locations. The weight of each film strip was taken and the weight variation was calculated.

Thickness of the film

The thickness of the film was measured by using screw gauge at various points of film and the average thickness was calculated.

Folding endurance

The folding endurance is expressed as the number of folds required for developing visible cracks or breaking any given film. This gives an indication of brittleness or flexibility of the film. A 2x2 cm strip was subjected to this test by folding the film at the same point repeatedly several times until a visible crack was observed.

Disintegration time

Disintegration time study was slightly modified to mimic the in vitro and in vivo conditions. For the study, 2 x2 cm film required for dose delivery was placed in a petri plate with 5 ml of pH 6.8 phosphate buffer. The time taken for the disintegration of the film was measured as the disintegration time. This test was followed in the present study, evaluation was done in triplicates and the standard deviation from the mean value was reported time required for the film to break and disintegrate was noted as in vitro disintegration time.

Table 5: Evaluation of FDFs prepared with natural polymers

Formulation

code

Weight

variation (mg)

Folding

endurance

Content

uniformity (mg)

 Assay (%)

Thickness

(μg)

Disintegration

time (s)
FN1 64.66±0.577 155 19.88±0.090 97.4 72±4.47 21.33±0.577
FN2 78.33±0.577 160 19.94±0.069 99.8 76±5.47 15.66±0.577
FN3 61.33±0.577 160 19.85±0.143 97.0 74±5.47 34±1.00
FN4 67.66±0.577 155 19.84±0.126 96.8 68±4.47 48±1.00
FN5 65.66±0.577 150 19.61±0.529 97.6 56±5.47 31.66±0.577
FN6 62.33±0.577 150 19.81±0.13 96.2 64±5.47 58±1.00
FN7 74.33±0.577 160 19.94±0.030 99.6 116±5.47 26.33±0.577
FN8 87.33±1.15 165 19.50±0.470 97.3 84±5.47 17.66±0.577
FN9 73.33±0.577 160 19.90±0.030 95.4 92±4.47 37.33±0.577
FN10 71.66±0.577 155 19.80±0.145 96.3 94±5.47 53.33±0.577
FN11 70.66±1.15 165 19.61±0.491 97.2 77±4.47 31.66±0.577
FN12 68.33±1.15 160 19.79±0.080 96.5 88±2.73 59.33±0.577

Table 6: Evaluation of FDFs prepared with synthetic polymers

Formulation

code

Weight

variation (mg)

Folding

endurance

Content

uniformity (mg)

Assay

(%)

Thickness

(μg)

Disintegration

time (s)
FS1 128.33±0.577 150 18.88±0.090 96.2 104±5.47 49.33±0.577
FS2 97.33±1.154 150 19.12±0.140 97.0 88±4.47 56.33±0.577
FS3 92.66±0.577 160 19.64±0.045 99.7 84±4.47 37.66±0.577
FS4 89.66±0.577 150 19.0±0.025 97.5 78±8.94 40.66±0.577
FS5 120.66±0.577 155 19.16±0.056 95.2 94±4.47 59.66±1.15

In vitro dissolution studies

The in vitro dissolution studies were conducted using 0.1N HCl and pH 6.8 phosphate buffer (900 ml). The dissolution studies were carried out using six basket dissolution apparatus at 37±0.5 °C and at 50 rpm. Each 2 x 2 cm film was submerged into dissolution media. Samples were withdrawn at 1, 3, 5, 10, 15 and 30 min time intervals and filtered through Whatman filter paper and were analyzed spectrophotometrically at 222 nm. To maintain the volume, an equal volume of fresh dissolution medium maintained at same temperature was added after withdrawing samples. The absorbance values were converted to concentration using standard calibration curve previously obtained from the study.

Table 7: Dissolution data of the optimized formulation in 6.8 pH phosphate buffer

Time (min) % drug release
0 0
1 30.0
3 73.0
5 86.5
10 97.5
15 109.3

Table 8: Dissolution data of the optimized formulation in 0.1N HCl

Time (min) % drug release
0 0
1 64.0
3 76.8
5 91.8
10 100.66
15 -

RESULTS AND DISCUSSION

In the present study, each FDF of 2x2 cm in size contained 20 mg of Eletriptan hydrobromide. The films were prepared using natural and synthetic polymers, amongst which the films of natural polymers disintegrated faster than the films of synthetic polymers. The films dissolved completely within one minute. The prepared films were tested for various parameters weight variation, thickness, folding endurance, disintegration and dissolution results are showed in table 5. FN2 was chosen as optimized formulation as it had a shortest D. T of 16 s. The dissolution studies were carried out in 6.8 pH phosphate buffer and 0.1N HCl, FN2 showed a percentage release of upto 100% within 10 min in both mediums.

A comparative study of drug release of optimized formulation and the pure drug was done in 6.8 pH phosphate buffer, and 0.1N HCl which showed the optimized formulation FN2 showed a faster drug release than pure drug as in fig. no 5 and 6.

Fig. 5: Comparison of dissolution profiles of optimized film and pure drug EHBR in 6.8 pH phosphate buffer


Fig. 6: Comparison of dissolution profiles of optimized film and pure drug EHBR in 0.1N HCl

CONCLUSION

The optimized FDF FN2 had good mechanical strength, with uniform thickness, high folding endurance, shorter DT and faster dissolution when compared to conventional tablets. The preparation of FDF did not require the addition of any disintegrant separately, so this formulation seems to be an attractive alternative to conventional marketed formulations.

CONFLICT OF INTERESTS

Declare none

REFERENCES

  1. Rasool Hassan. Overview on drug delivery system. Pharm Anal Acta 2012;3:2153-35.
  2. Prasana Desu, Manoranjan Sahu. Formulation and evaluation of fast dissolving films of zolmitriptan. Int Res J Pharm 2012;3:373-6.
  3. Alpesh Patel R, Dharmendra Prajapati S, Jignyasha Raval A. Fast dissolving films (FDFs) as a newer venture in fast dissolving dosage forms. Int J Drug Dev Res 2010;2:232-46.
  4. Dipika Parmar, Upendra Patel, Bhavin Bhimani, Aditi Tripathi, Dhiren Daslania, Ghanshyam Patel. Orally fast dissolving films as a dominant dosage form for quick release. Int J Pharm Res Bio-sci 2012;1:27-41.
  5. Suresh B, Halloran D, James L. Quick dissolving films: a novel approach to drug delivery. Drug Dev Tech; 2006. p. 1-7.
  6. Samita Gauri, Gaurav Kumar. Fast dissolving drug delivery and its technologies. Pharma Innovation 2012;1:34-9.
  7. Swapnil Patil L, Paresh Mahaparale R, Madhavi Shivnikar A, Shradha Tiwari S, Ketan Pawar V, Prashant Sane N. Fast dissolving oral films: an Innovative drug delivery system. Int J Res Rev Pharm Appl Sci 2012;2:482-96.
  8. Dixit RP, Puthli SP. Oral strip technology: overview and future potential. J Cont Release 2009;139:94-107.
  9. Gowri R, Narayan N, Revathy S, Prabhavathy G, Preethy Mol G, Rekha G. Melt in mouth films–an effective alternative drug delivery system. Int J Biol Pharm Res 2013;4:645-50.
  10. Kai Bin Liew, Yvonne Tze Fung Tan, Kok K Khiang Peh. Characterization of oral disintegrating film containing donepazil for the alzhemier disease. AAPS PharmSciTech 2012;13:134-42.
  11. Karthikeyan D, Sanju Sri, Santhosh Kumar C. Development of fast dissolving oral film containing rizatriptan benzoate as an antimigraine medication. Indo Am J Pharm Res 2013;3:2642-54.
  12. Indian Pharmacopoeia. Vol 2. Delhi: Government of India ministry of health and family welfare; 2014.

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