Formulation and evaluation of

““FORMULATION AND FORMULATION AND EVALUATION OFEVALUATION OF FAST DISSOLVING TABLET FAST DISSOLVING TABLET DOSAGE DOSAGE FORM” FORM”

PREPARED BY: Gajanan S. Ingole

GUIDED BY : K. B.

Charhate

DEPARTMENT OF PHARMACEUTICSANURADHA COLLEGE OF PHARMACY, CHIKHLI.

2012-2013.

Introduction.

Review of literature.

Drug profile.

Excipients.

Aim & objectives.

Plan of work.

Materials & Equipments

Experimental work.

Result & Discussion.

Conclusion.

References.

CONTENTS :

US FDA defined ODT as “A solid dosage form

containing medicinal substances which disintegrates rapidly

usually within a matter of seconds, when placed upon the tongue”.

Recently, ODT have started gaining popularity and acceptance as new drug delivery systems, because they are easy to administer and better patient compliance, especially in elderly and children.

Orodispersible tablets are also known as Mouth dissolving tablets, Orally disintegrating tablets, Melt‐in‐mouth, Fast dissolving drug delivery, Rapimelts tablets, Porous tablets, Quick dissolving tablets etc.

Defination :

Orodispersible tablets (ODT) are oral solid dosage forms that

disintegrate in the oral cavity in easy swallow residue.

faster the drug goes into solution, quicker the absorption and onset

of clinical effect, as the saliva passes down into the stomach. In such

cases, bioavailability of drug is significantly greater than those

observed from conventional tablets dosage form.

Recently ODT terminology has been approved by United States

Pharmacopoeia, British Pharmacopoeia and Centre for Drug

Evaluation and Research (CDER).

Advantages of fast dissolving drug delivery system

Ease administration for patients who are mentally ill, disabled

and uncooperative.

No water needed.

Can be designed to leave minimal or no residue in mouth

It provide a pleasant mouth feel.

No chewing needed.

Better taste obtained by taste masking.

Improved stability, low sensitivity to environmental condition

Disadvantage of Mouth Dissolving Tablets:

Drugs with relatively larger doses are difficult to formulate into

FDT e.g. antibiotics

Patients who concurrently take anticholinergic medications may

not be the best candidates for FDT.

patients with Sjogren's syndrome or dryness of the mouth due

to decreased saliva production may not be good candidates for

these tablet formulations.

Need to formulate fast dissolving tablets

Geriatric patients mainly suffering from conditions like

hand tremors and dysphasia.

Pediatric patients who are unable to swallow easily because

their central nervous system and internal muscles are not

developed completely.

Traveling patients suffering from BP and angina pectoris

that do not have easy access to water.

Mentally challenged patients, bedridden patients and

psychiatric patients.

The ideal characteristics of a drug for fast dissolving tablet

1. Ability to permeate the oral mucosa.

2. Have the ability to diffuse and partition into the epithelium

of the upper GIT.

3. Small to moderate molecular weight.

4. Low dose drugs preferably less than 50 mg.

5. Short half life and frequent dosing drugs are unsuitable for

ODT.

6. Very bitter or unacceptable taste and odour drugs are

unsuitable for ODT.

TECHNIQUES FOR SOLUBILITY ENHANCEMENT

Inclusion Complex Formation Techniques

Grinding method:

Drug and carriers were blended in desired proportions using

spatula for 10 minutes and then ground in mortar with pestle. The

co-grinding mixture was then passed through sieve #40 and stored

in desiccator until further use.

eg. Cyclodextrine

Advantages of cyclodextrin complexes

It improves bioavailability from solid formulations.

Stability and shelf life can be increased.

Gastrointestinal irritation may be reduced.

Complexation prevents drug-drug or drug-additive interaction.

It can be used to mask unpleasant odor and taste.

2. REVIEW OF LITERATURE:-

1) Vikas Agarwal et al: Encyclopedia of pharmaceutical technology, Third edition,Volume 2;stated that A large number of companies are in the ODT drug.As pharmaceutical companies are now starting to recognize the need for more technological advances to meet the new challenges in the future, DDT continues to have a significant impact and contribution in meeting those demands and challenges.

2)Abu-Izza et al: Patent on Fast dissolving tablet; shows the present invention relate to the process for preparation of tablet which dissolve rapidly in the mouth and provide an excellent mouthfeel. The tablet of the invention comprise a compound which melt at about 370C.or lower, have a low hardness, high stability and generally comprise a few insoluble disintegrant which may cause a gritty or chalky sensation in the mouth

Convenient and economically feasible processes by which the tablet of the invention may be produced are also provided.(United States Patent, Patent No. US 6,733,781 B2)

.

3) Jain et al: Patent on Rapidly disintegrating solid dosage form; stated that the rapidly disintegrating solid dosage form of poorly soluble active ingredient and at least one pharmaceutically acceptable water- soluble or water-dispersible excipient, where in poorly soluble active ingredient particles have an average diameter, prior to inclusion in the dosage form, of less than about 2000nm.the dosage form of the invention has the advantage of combining rapid presentation and rapid dissolution of the active ingredient in oral cavity(.(United States Patent, Patent No. US 6,316,029 B1)

4) Sahu Chandra Mohan et al: Recent advances in orodispersible tablets: A Review; studied on The techniques and technologies described in this article represent how recent advances in formulation development and processing technologies make the efforts to achieve orodispersible tablets, conclude that the basic approach followed by all

Felodipine

(Calcium channel blocker)

Category : Antihypertensive and antianginal.

Structural formula :

Molecular formula : C18H19Cl2NO4

DRUG PROFILE

13

Molecular weight : 384.25

Description : Slightly yellowish & Crystalline powder.

Solubility : It is insoluble in water & freely soluble in ethanol & dichloromethane.

Melting point : 142-1450c

Dose : 5mg ones a day

Bioavailibility : 15%

Absorption : Completely absorbed from g.i.t

Metabolism : Metabolised in gut & liver.

Excipients

14

AIM :

Formulation of fast dissolving tablet and evaluate them to

get optimized result.

OBJECTIVES :

1.For rapid dissolution of drug and absorption which may produce

rapid onset of action.

2. To avoid first pass metabolism

3.To Improved patient compliance.

4. It can be designed to leave minimal or no residue in mouth .

5. To improved biopharmaceutical properties and better safety

compared with conventional oral dosage forms.

PLAN OF WORK:

1. Literature survey.

2. Procurment of drug, polymer & other excipients

for the study.

3. Selection of material of required standard &

qualitative analysis of raw material

4. Pre-formulation studies.

5. Preparation of various formulae for study.

6) Evaluation of tablet.

a)Tablet appearance.

b)Thickness.

c)Diameter.

d)Hardness.

e)Friability.

f)Weight variation.

g)Assay of tablet.

h)Disintegration study

i)Dissolution study

Sr. no Ingredients Grade Suppliers

1 Felodipine PharmaAjanta pharma Ltd,Mumbai

2Cross carmellose sodium

Pharma FDC Ltd, Mumbai

3 Crosspovidone PharmaLeben Laboratories

Pvt. Akola

4 Sodium starch glycolate PharmaLeben Laboratories

Pvt. Akola

5 Microcrystalline cellulose PharmaLeben Laboratories

Pvt. Akola

6 Magnesium stearate PharmaLeben Laboratories

Pvt. Akola

7 Talc PharmaLeben Laboratories

Pvt. Akola

8 Mannitol AR Rajesh chemicals

Materials & Equipments

Table : List of Excipients

Sr. No

Instruments Manufacturer

1 Electronic Balance Dolphin,Mumbai.2 Tablet compression machine Cadmach, Ahemadabad.3 Electronic balance Dolphin,Mumbai.4 Friability Test Apparatus Roche Friabilator5 Vernier Caliper Mitutoyo,Japan

6 Tablet Dissolution TesterElectro Lab.(USP XX III) (DTD-

06P)

7 Ultra violet SpectrophotometerUVvisible Double Beam, Elico.

(SL218).

8 Fourier Transform Infra RedIR affinity-1,FTIR-

8001:Shimadzu,Japan9 Digital pH meter Equip-Tronics,EQ-610.

10 Hot Air OvenShreeji pharmaceuticals,scientific

lab Mumbai,India.

Table: List of Equipments

Equipments

EXPERIMENTAL WORK :

SPECTRAL ANALYSIS OF FELODIPINE

Differential Scanning Colorimery

DRUG –POLYMER INTERACTONS

Fourier transform infrared spectroscopy

PREPARATION OF BUFFERS AND REAGENTS

1 Sodium hydroxide solution (0.1 N)

2 Monobasic sodium phosphate monohydrate(1 M)

3 Dibasic sodium Phosphate anhydrous(0.5M)

4 Phosphate buffer solution (pH 6.5)

FTIR Spectra of Felodipine

DSC of Felodipine

FTIR spectra of Felodipine physical mixture.

DETERMINATION OF λ MAX

It shows maximum absorbance (λ max) : 312.2 nm

Standard Calibration Curve In phosphate buffer pH 6.5

Concentration(µg/ml)

Absorbance

0 0

10 0.09

20 0.1811

30 0.2737

40 0.3448

50 0.4235

Table : Conc. And absorbance

From the standard curve of Felidipine, it was observed that the drug obeys

beer’s law in concentration range of 10 to 50 µg/ml against absorbance at

312 nm. in 6.5 phosphate buffer. The linear regression equation generated

was used for the calculation of amount of drug release. The value of R2 is

0.997.

FORMULATION DESIGN

Direct Compression Method

Sr.No Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9

1 FD+β-CDN complex 10 10 10 10 10 10 10 10 10

2 CP 3 6 9 - - - - - -

3 CCS - - - 3 6 9 - - -

4 SSG - - - - - - 3 6 9

5 Avicel pH101 10 10 10 10 10 10 10 10 10

6 Talc 6 6 6 6 6 6 6 6 6

7 Mg.streate 2 2 2 2 2 2 2 2 2

8 Mannitol 89 86 83 89 86 83 89 86 83

Total 120 120 120 120 120 120 120 120 120

Table : Composition of Fast dissolving tablet formulation containing Felodipine

The ingredients used in the manufacture of tablets for the batches F1 to F9 are shown in the Table

*FD-Felodipine,*CP-crospovidone,*CCS-crosscarmellose sodium,*SSG-sodium starch glycolate

Physical properties

Bulk density.

Tapped density.

Carr´s Compressibility index.

Hausner’s ratio.

Angle of repose.

Table : Physical properties of the powder-blends of the batches F1 to F3

Parameter F1 F2 F3

Bulk density (gm/cc)

Tapped density (gm/cc)

Angle of repose,

Compressibility index (%)

Hausner’s ratio

0.57

0.68

43.15

16.17

1.19

0.47

0.73

41.81

35.61

1.55

0.54

0.72

28.60

18.51

1.29

Parameter F4 F5

F6



Angle of repose,


Hausner’s ratio

0.58

0.78

27.34

10.00

1.34

0.56

0.78

40.10

28.20

1.39

0.58

0.77

48.23

24.67

1.32


Parameter F7 F8 F9



Angle of repose,


Hausner’s ratio

0.58

0.70

26.56

17.14

1.20

0.61

0.72

32.46

15.20

1.18

0.59

0.70

36.32

15.71

1.18


1. Thickness.

2. Diameter.

3. Hardness.

4. Friability.

5. Weight variation.

6. Assay of tablet.

7. Disintegration study

8. Dissolution study

Evaluation parameter of

tablet.

Sr.No. Parameters F1 F2 F3

1. Thickness (mm 2.5 2.6 2.5

2 Diameter (mm) 6 6 6.1

3 Hardness (kg/cm2. ) 2.86 3.3 2.8

4 Friability (%) 0.81 0.40 0.48 5 Uniformity of weight (mg) 121±10% 116±10 121±10

6 Drug content (%) 96.35 95.87 99.20

7 Disintegration time(sec) 137 129 116

Table: Post compression parameter of fast dissolving tablets for the batches F1 to F3

Sr.No. Parameters F4 F5 F6

1 Thickness (mm) 2.9 2.8 2.7

2 Diameter (mm) 6.1 6 6

3 Hardness (kg/cm2) 3.6 3.8 2.6

4 Friability (%) 0.97 0.48 0.97

5 Uniformity of weight (mg) 122±10 122 ±10 127±10

6 Drug content (%) 96.72 94.5 92.26

7 Disintegration time(Sec) 140 132 126

Table : Post compression parameter of fast dissolving tablets for the batches F4 to F6

Sr. No. Parameters F7 F8 F9

1 Thickness (mm) 2.6 2.6 2.6

2 Diameter (mm) 6.1 6 6.1

3 Hardness (kg/cm2. 4.2 3.5 3.7

4 Friability (%) 1.1 0.40 0.88

5 Uniformity of weight (mg) 125±10 122±10 124±10

6 Drug content (%) 96.72 94.74 97.03

7 Disintegration time(Sec) 138 141 134

Table : Post compression parameter of fast dissolving tablets for the batches F7 to F9

Sr.No. Time (Min) % Drug Release

F1 F2 F3

1 1 38.55 15.72 18.28

2 3 54.55 24.60 28.6

3 5 72.47 33.90 39.42

4 10 76.89 52.81 61.41

5 15 73.09 66.60 77.89

6 30 89.07 77.89 90.58

7 45 94.92 84.44 98.18

0

20

40

60

80

100

120

0 10 20 30 40 50

F1

F2

F3

Time(min)

%D

rug

Rel

ease

Comparative dissolution profile of F1, F2,F3

Table : In vitro release of felodipine from tablets for the batches F-1 to F-3

Figure : In vitro release of felodipine from the tablets for the batches F1, F2 and F3.

Sr.No. Time (Min) % Drug Release

F4 F5 F6

1 1 24.42 36.87 39.64

2 3 28.60 40.48 39.64

3 5 31.65 46.69 54.20

4 10 43.20 53.02 57.08

5 15 51.42 66.39 64.16

6 30 66.93 78.95 80.64

7 45 81.19 88.63 93.76

0102030405060708090

100

0 10 20 30 40 50

F4

F5

F6

Time (Min)

Comparative dissolution profile of F4, F5,F6

%D

ru

g R

ele

ase

Figure: In vitro release of felodipine from the tablets for the batches F4, F5 and F6.


Sr. No. Time (Min) % Drug Release

F7 F8 F9

1 1 19.75 24.75 28.33

2 3 26.98 30.11 35.19

3 5 37.13 36.70 41.10

4 10 50.35 48.75 48.75

5 15 53.86 63.41 61.93

6 30 70.3 76.73 78.95

7 45 80.14 88.21 92.09Figure : In vitro release of felodipine from the tablets for the batches F7, F8 and F9


1. Suitable analytical method based on UV-Visible spectrophotometer was developed for felodipine. λmax of 312.2 nm was identified in methanol and 311 nm in phosphate buffer solution, pH 6.5.

2. From the FT-IR spectra the interference was verified and found that felodipine did not interfere with the excipients used.

3. Direct compression method was established to manufacture fast dissolving tablets of felodipine.

4. Fast dissolving tablets of felodipine were successfully prepared using croscarmellose sodium, sodium starch glycolate, crospovidone.

SUMMARY AND CONCLUSION

SUMMARY

5. In the present study, fast dissolving tablets were prepared using single superdisintegrant in each formulation

6. Evaluation parameters like hardness, friability, weight variation and drug content indicate that values were within permissible limit for all formulations.

7. In vitro drug release study was carried out and based on the results; F-3 was identified as the best formulation among all the other formulations and In vitro release profiles was more than 98% within 45 minutes.

8. The formulation F-3 contains croscarmelose a polymer which causes the disintegration by capillary action. It causes the in vitro dispersion within 45 min.

and hence the formulation F3 was optimized after conducting the reproducibility study.

CONCLUSION

The conclusions arrived in this thesis indicated that the Fast dissolving

tablet of felodipine developed in this investigation releases drug

batter than conventional tablet drug release, based on in vitro release

studies. Further studies are needed to investigate these formulations

for its performance in vivo.

Thus the objectives of the present thesis are achieved.

The result of the study indicates that fast dissolving tablet of felodipine

that can be successfully prepared.

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Education

Formulation and evaluation of