Formulation and Evaluation of Orodispersible Tablets of an Antiulcer Agent

 

Srinivasa Sastry D1, Narayana Charyulu R2, Satyanarayana D S, Srilakshmi D

1Department of Pharmaceutics, Aditya College of Pharmacy, Surampalem, Rajahmundry, Andhra Pradesh-533102, India.

2Department of Pharmaceutics, N G S M Institute of Pharmaceutical Sciences, Nitte University, Paneer, Deralakatte, Mangalore, Karnataka – 575 018, India

*Corresponding Author E-mail: narayana@nitte.edu.in

 

ABSTRACT:

In the present work, an attempt has been made to formulate oral dispersible tablets of omeprazole by three different methods. Conventional tabletting procedure was followed for the preparation of tablets. Three batches omeprazole were prepared and evaluated for general appearance and physical parameters, drug content, in vitro disintegration, in vitro dispersion, in vitro drug release, kinetics and stability studies. Formulations prepared by omeprazole superdisintegrants addition method emerged as the best formulations, as they showed rapid in vitro disintegration time, in vitro dispersion time and drug release at the end of 5 min, apart from taste and excellent mouth feel compared to other methods.  It was concluded that oral dispersible tablets of anti ulcer agents can be successfully formulated and will be used as a novel drug dosage form for pediatrics and geriatrics with improved patient compliance. 

 

KEYWORDS:  Omeprazole, Orodispersible tablets, Superdisintegrants.

 

 


INTRODUCTION:

Recent developments in technology have presented viable dosage alternatives for patients who have difficulty in swallowing the tablets or liquids. Traditional tablets and capsules administered with aglass of water may be inconvenient or impractical for some patients. Dysphagia or chewing solid dosage forms, which is a common problem of all age groups, particularly pediatrics and geriatrics, because of physiological changes associated with these groups.1

 

Dysphasia is also associated with the number of medical conditions, including stroke, Parkinson’s disease, AIDS, head and neck radiation therapy and other neurological disorders, including cerebral palsy.

 

Other categories that experience problems using conventional oral dosage forms include are mentally ill, uncooperative and nauseated patients, those with motion sickness, sudden episodes of allergic attack or coughing,2,3 sometimes, it may be difficult to swallow the conventional products due to unavailability of water.4

 

These problems cause the need for delivering drugs to patients efficiently, and with few side effects have prompted pharmaceutical companies to engage in the development of new drug delivery systems. Oral dispersible tablets (ODT) are perfect fit for all this kind of patients. ODT is those solid dosage forms when put on the tongue, disintegrate or dissolve instantaneously, releasing the drug, within a few seconds without the need of water. When this type of tablet is placed into the mouth, the saliva will serve to rapidly disintegrate the tablet5.

 

The faster the drug into solution, quicker the absorption and onset of clinical effect. ODT release drug in the mouth for absorption through local oral mucosal tissues and through pregastric (i.e., oral cavity, pharynx and oesophagus), gastric (i.e., stomach) and post gastric (i.e., small and large intestine)6,7. In such cases, the bioavailability of some drugs may be increased due to absorption of drugs in oral cavity and also due to pregastric absorption of saliva containing dispersed drugs that pass down significantly greater than those observed from conventional dosage forms8,9. ODT are also known as fast dissolving, mouth dissolving, rapid-dissolve, quick disintegrating, orally disintegrating, rapimelt, fastelts, melt-in-mouth, quick dissolving, porous tablets, EFVDAS or Effervescent Drug Absorption System10. ODT technology has been approved by United States Pharmacopoeia (USP), Centre for Drug Evaluation and Research (CDER). US- FDA defined ODT as A solid dosage form containing medicinal substances, which disintegrates rapidly, usu- ally within a matter of seconds, when placed upon the tongue.   Recently,   European   Pharmacopoeia   also adopted the term Oro Dispersible Tablet11.

 

Cancer chemotherapy causes a lot of adverse effects, of which nausea and vomiting are prime one. This can be clearly seen with model anticancer drug cisplatin, which is first line drug in many types of cancers. Hence anti ulcer drugs like omeprazole, pantoprazole are administered one hour prior to the administration of anticancer drug. However, this becomes a major patient non compliance in the case of children, elderly and bed ridden patients for whom swallowing tablets causes inconvenience. Among the dosage forms developed to facilitate ease of medication. The rapid disintegrating tablet (RDT) is one of the most widely employed commercial products. Hence, present investigation is an attempt to improve patient compliance by formulating anti- ulcer drugs in the form of oral dispersible tablets12.

 

MATERIALS AND METHODS:

Materials:

Omeprazole was obtained as a gift sample from Mylan Pharmaceuticals, Hyderabad. Croscarmelose sodium, Crospovidone, Sodium bicarbonate, Citric acid, Ammonium bicarbonates were procured from Ozone international, Mumbai. All other chemicals used were of analytical grade.


 

Table 1: Composition of ODT of drugs-Superdisintegrants addition

Ingredients (mg/tab)

Formulation Code

OSD1

OSD2

OSD3

OEV1

OEV2

OEV3

OSL1

OSL2

OSL3

Omeprazole

40

40

40

40

40

40

40

40

40

Croscarmelose sodium

12.5(5%)

 

12.5 (5%)

-

-

 

-

-

-

Crospovidone

7.5 (3%)

12.5 (5%)

 

-

-

 

-

-

-

Sodium starch glycolate

-

7.5 (3%)

7.5 (3%)

-

-

-

-

-

-

Sodium Bicarbonate

-

-

-

25(10%)

20 (8%)

25(10%)

-

7.5 (3%)

7.5 (3%)

Citric acid (Anhydrous)

-

-

-

20(8%)

15 (6%)

25(10%)

-

-

-

Ammonium Bicarbonate

-

-

-

-

-

-

150 (60%)

100 (40%)

50 (20%)

Avicel pH102

134.25

134.25

134.25

50

50

50

-

-

-

Mannitol (30%)

75

75

75

129.75

129.75

129.75

75

75

75

Aerosil (2%)

5

5

5

-

-

-

-

-

-

Sodium saccharin (1.6%)

4

4

4

4

4

4

4

4

4

Purified Talc (2%)

5

5

5

5

5

5

5

5

5

Magnesium stearate (1.2%)

3

3

3

3

3

3

3

3

3

Strawberry flavor (1.5%)

3.75

3.75

3.75

3.75

3.75

3.75

3.75

3.75

3.75

 


Methods:

Formulation of orodispersible Tablets:

In the present study, orodispersible tablets of Omeprazole were prepared by direct compression technique.

 

Preparation of ODT of Omeprazole using Superdisintegrant addition Method:

The superdisintegrants used were croscarmelose sodium, crospovidone and sodium starch glycolate. All the ingredients were passed through a sieve #40 and kept in a hot air oven at 80 ˚C to make anhydrous and accurately weighed. The drug, superdisintegrants, Avicel pH 102, mannitol sweetener, aerosol, and flavor were triturated well in a mortar to mix them properly. Magnesium stearate and talc were then passed through a sieve #80, mixed and blended with the initial mixture. The mixed blend of drug and excipients was compressed using rotary punch MINIPRESS II (Karnavathi) tabletting machine to produce tablet weighing 200 mg having a diameter of 8 mm. Following above procedure, three batches of ODT of omeprazole in a different ratio were prepared.

 

Evaluation of orodispersible Tablets:

Hardness and Friability:

Hardness and Friability of tablets were determined as per IP by using Monsanto hardness tester and Roche Friabilator respectively 12.

 

Wetting time:

A piece of tissue paper folded twice was placed in a small petri dish containing 6 ml of simulated saliva pH (phosphate buffer pH 6.8). A tablet was put on the pa- per and the time required for complete wetting was measured. Six trials for each batch were performed and an average time for wetting with standard deviation was recorded 12.

 

Surface pH:

The surface pH of the tablets was determined in order to investigate the possibility of any side effects due to change in pH in vivo since an acidic or alkaline pH may cause irritation to the buccal mucosa. A combined glass electrode was used for the purpose. The tablets were allowed to swell by keeping them in contact with 1 ml of simulated saliva for 2 h and pH was noted by bringing the electrode in contact with the surface of the formulations (Wade A and Weller PT, 1984) and allowing it to equilibrate for 1 min.

 

Drug content estimation:

As per USP, twenty tablets were weighed and powdered. A quantity of powder equivalent to 10 mg of drug was accurately weighed, transferred into a 100 ml volumetric flask and dissolved in 0.1 N HCl. After shaking for 10 min, the volume was made up to 100 ml with 0.1 N HCl. The above solution (1 ml) was taken and diluted to 10 ml and was analyzed spectrophotometrically at 305 nm and percentage of Omeprazole, was determined13.

 

Weight variation test:

Uniformity of weight test as described in the IP was followed. Using this procedure weight variation range of all batches of formulations were determined and recorded.

 

Uniformity of drug content:

One tablet was powdered and transferred to a 100 ml volumetric flask and dissolved in 0.1N HCl. The volume was made up to 100 ml. From this 1 ml was pipetted out and diluted to 10 ml with 0.1N HCl in 10 ml volumetrical flask. The absorbance was measured spectrophotometrically at 305 nm for omeprazole. The test was carried out individually for five tablets from each formulation.

 

In vitro Disintegration time:

In vitro disintegration time was determined using a disintegration test apparatus (Thermonik). A tablet was placed in each of the six tubes of the apparatus and one disc was added to each tube.

 

In vitro Dispersion Time:

A tablet was put into a measuring cylinder containing 6 ml of phosphate buffer pH 6.8 (simulated saliva pH). Time required for complete dispersion of a tablet was recorded. This test was performed for six tablets from each batch and average time taken for dispersion with standard deviation was recorded13.

 

In vitro drug release studies:

In vitro drug release studies were carried out by using USP XXIII dissolution apparatus II (Paddle type) [Electro lab (TDT-06T) Tablet Dissolution Tester] at 50 rpm. The drug release profile was studied in 900 ml of hydrochloric acid buffer at pH 1.2 by maintaining at 37 ± 0.5 ˚C. Aliquots of 10 ml of a dissolution medium were with- drawn at specific time intervals (1, 2, 3, 4 and 5 min), filtered and the amount of drug released was determined spectrophotometrically at 305 nm13.

 

Stability Studies:

Twenty tablets from each batch were selected at random and were packed in aluminum foil. Ten tablets from each batch were kept in a desiccator at room temperature, and the other 10 were kept at room temperature on a shelf (at RH 80%) for one month. The tablets were checked for physical appearance, hardness, weight difference, in vitro dispersion time and in vitro drug release profile. Then the results were com- pared with those obtained immediately after compression.

 

RESULTS AND DISCUSSION:

The results of evaluation parameters of orodispersible tablets is shown in below table 2

 

All the ODT formulations by superdisintegrant addition method showed less in vitro disintegration time (< 23 sec) and in vitro dispersion time (< 26 sec). The formulation containing croscarmelose sodium (5% w/w) formulation OSD3 emerged to be the best. This is because of least hardness of 2.22 ± 0.12 Kg/cm and presence of croscarmelose sodium in higher concentration.

 

 


 

Table 2: Evaluation of orodispersible tablets

Formulation code

Hardness* ± SD (kg/cm2)

Disintegration Time (sec) ± SD

Dispersion Time (sec) ± SD

Wetting Time(sec)± SD

OSD1

2.40   ± 0.14

17.32 ± 0.66

21.50 ± 1.15

21.14± 2.40

OSD2

2.80 ± 0.22

22.12 ± 2.10

25.00 ± 2.10

24.04 ± 3.22

OSD3

3.20 ± 0.13

12.82 ± 1.12

16.00 ± 1.0

32.00 ± 3.02

OEV1

3.18 ± 0.16

40.80 ± 2.83

46.5 ± 2.92

50.14 ± 2.30

OEV2

2.86 ± 0.12

39.26 ± 2.73

42.31 ±3.50

52.00 ± 3.01

OEV3

3.10 ± 0.24

32.00 ± 2.0

40.64 ± 2.42

40.02 ± 1.84

OSL1

2.21   ± 0.05

25.00 ± 1.0

26.06 ± 2.41

34.15 ± 2.70

OSL2

2.50± 0.06

30.51 ± 1.31

30.12 ± 3.20

35.81 ± 3.20

OSL3

2.61 ± 0.20

31.33 ±  2.30

35.24 ± 3.18

40.00 ± 1.64


 


Figure 1: In vitro drug release profile of Orodispersible tablets

 


Among the superdisintegrant formulations croscarmelose less disintegration and dispersion time because it will draw water and swell. Crospovidone will increase disintegration time. As a result crospovidone will increase the disintegration and dispersion time.

 

As far drug content, weight variation, friability tests are concerned formulation were within IP limits. The surface pH is concerned all the formulations remained within 6.5-7.5 pH. Hence, it was found to be compatible with the oral cavity pH (6.8).

 

Wetting time of tablets of all formulations reflected in the disintegration time and dispersion time (Table 2) and in vitro release profile (Fig 1).

 

Stability studies indicated that no significant variation was found as far as physical and in process parameters of formulations were concerned. Hence, the formulations were found to be stable.

 

CONCLUSION:

The oral dispersible tablets of omeprazole were prepared by superdisintegrant addition method. Further, the formulation parameters reflected in the release of drug from the formulations. Hence, the methods employed to prepare the formulations of ODT found to be effective and the formulations were found to be better patient compliance, especially for pediatrics and geriatrics.

 

ACKNOWLEDGEMENT:

The authors wish to acknowledge Aditya College of Pharmacy, for providing the necessary facilities and financial support to carry out this project. Further, the authors are also grateful to Mylan Laboratories Pvt Ltd, Hyderabad, Andhra Pradesh, for providing free sample of Omeprazole.

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Received on 17.01.2017             Modified on 16.02.2017

Accepted on 12.03.2017           © RJPT All right reserved

Research J. Pharm. and Tech. 2017; 10(3): 747-750.

DOI: 10.5958/0974-360X.2017.00140.8