Formulation and Evaluation of Fast Disintegrating Tablet of Atenolol Using Modified Okra Gum as Natural Super Disintegrant

Fast dissolving drug delivery systems

(FDDDS) are formulations designed to disintegrate or dissolve rapidly in the oral cavity, allowing for quick drug release and absorption. These systems are particularly beneficial for patients who may have difficulty swallowing tablets or capsules, such as paediatric and geriatric populations, as well as those with certain medical conditions. (Jadhav SD et al., 2012) These were first came into existence in 1970 as an alternative to tablets, syrups and capsules, for pediatric and geriatric patients which rapidly disintegrate and dissolve in saliva and then easily swallowed without need of water which is a major benefit over conventional dosage form The FDTs dissolve or disintegrate within 60 seconds when placed in the mouth without drinking or chewing. The active ingredients are absorbed through mucous membranes in the mouth and GIT and enter the blood stream. But due to certain disadvantages of fast dissolving tablets like: their physical solid form, sometimes difficult to carry, store and handle, leave unpleasant taste/grittiness in mouth if not formulated properly. Psychological fear of swallowing, chewing or choking, low pressure moulded tablets fabricated by different manufacturing methods and their expensive packaging cost.

• 1. Advantages of fast dissolving drug delivery systems
• Ease of Administration: FDDDS typically eliminates the need for water or other liquids for administration. This is particularly advantageous for patients who may have difficulty swallowing tablets or capsules, such as pediatric, geriatric, or bedridden patients. Suitable for patients with swallowing disorders, dysphagia, or those who experience difficulty in ingesting traditional oral dosage forms.
• Improved Patient Compliance: The convenience of fast dissolving formulations enhances patient compliance. Patients are more likely to adhere to their medication regimens when the dosage form is easy to use and doesn't require additional steps like swallowing with water. Particularly beneficial for individuals who have an aversion to swallowing pills.
• Rapid Onset of Action: FDDDS allows for quick drug release and absorption due to the rapid dissolution or disintegration of the dosage form in the oral cavity. Suitable for drugs where rapid onset of action is crucial, such as analgesics or anti-allergic medications.
• Improved Bioavailability: The rapid dissolution of drugs in FDDDS can enhance their bioavailability. This is important for drugs with low solubility or those that undergo significant first-pass metabolism. Enhanced absorption can lead to improved therapeutic outcomes.
• Convenience for Caregivers: Caregivers, including healthcare professionals or family members, find FDDDS convenient to administer to patients who may have difficulty taking conventional tablets or capsules. Reduces the need for assistance in administering medications, especially in non-hospital settings.
• Discreet and Portable: FDDDS often comes in discreet packaging and is easily portable. This is beneficial for patients who need to take medications outside their homes or in public places. Convenient for patients with busy lifestyles or those who may need to carry medications with them.
• Taste Masking: Many FDDDS formulations are designed with taste-masking technologies, making them more palatable and improving patient acceptance. Especially important for pediatric patients who may resist medication due to unpleasant taste.
• Reduced Risk of Choking: Since FDDDS dissolves or disintegrates rapidly in the mouth, there is a lower risk of choking compared to traditional solid dosage forms. It's important to note that while FDDDS provides these advantages, the choice of the appropriate formulation depends on the specific drug, patient population, and therapeutic requirements. Additionally, considerations such as stability, manufacturing processes, and cost-effectiveness play a role in the development and adoption of fast dissolving drug delivery systems.

MATERIALS AND METHOD

MATERIALS

Atenolol was procured as a gift sample from Medrich Ltd. Bangalore. Okra, Sodium starch glycolate, Magnesium stearate, mannitol, talc, meglumine and MCC used were of analytical grade. All the ingredients and their uses in formulation of tablet were shown in Table no. 1.

Table no. 1: Ingredients used in formulation of tablet

METHODS

Preformulation studies

UV spectrophotometric analysis

Lambda max is the wavelength of light in the ultraviolet region at which maximum absorbance is exhibited by the compound. Sample was dissolved in water to prepare stock solution and scan in UV spectrophotometer. Atenolol was estimated by UV visible spectroscopy. Spectrophotometric estimation of atenolol was carried out in pH 6.8. The study was carried out in triplicates. 100mg of drug was placed in volumetric flask and dissolved in pH 6.8 buffer. From this solution, 10 ml solution was withdrawn and further diluted to 100 ml with buffer to yield the standard stock solution of atenolol (100 µg/ml).

Melting point

Melting point is one of the identification tests for organic compounds. The melting point of the drug was determined by capillary melting point method using melting point apparatus (Tempo, India). The drug was filled in a thin-walled capillary tube, with sealed one end. The capillary was then placed in melting point apparatus and the temperature of the apparatus was gradually increased. The temperature range over which the drug melts was observed.

Solubility

The solubility studies of drug in aqueous and non-aqueous phases are the important properties during formulation consideration and behaviour and transport of drugs in the body. Equilibrium solubility was determined at room temperature, for this, systems of each solvent (DW, Ether, Chloroform, Methanol, Ethanol & PBS pH 6.8) were taken individually in volumetric flask and drug was added gradually in each solvent and vigorously shaken on shaker. As the saturation point was reached a pinch of drug was added to it and the flask was shaken for 15min and placed in the flask shaker for 24 hrs. After 24 hrs it was removed and observed. Since un-dissolved drug was found it was kept for 24hrs undisturbed. After 24 hrs, the solution was filtered and diluted suitably with reagent blank and absorbance was taken against reagent blank and recorded.

Preparation of standard calibration curves

10 mg of atenolol was weighed accurately and transferred to 100 ml volumetric flask and dissolved in small amount of water, after that volume was made up to 100 ml with water so as to obtain stock solution of 100 µg/ml. Stock solution was taken in aliquots of 0.1 ml, 0.2 ml, up to 0.5 ml in to a series of 10 ml volumetric flasks and volume was made up to the mark with water. The solutions were filtered through Whatman filter paper no. 1 and filtrate was analyzed at λmax 225nm using UV visible spectrophotometer. water was used as blank solution. The standard curve was plotted between absorbance and concentration.

Drug- excipients compatibility studies

Drug excipients compatibility study was done by using I.R. spectroscopy different mixtures of drug and carrier were prepared and analysed by I.R. in the range of 400- 4000 cm-1. Small amount of sample was taken and analysed by placing it in powder sample compartment and it was check for any interaction between drug and excipients. (Badola et al., 2015)

Extraction and isolation of okra mucilage Method of extraction:

Okra was obtained from local market. Collected okra was carefully washed and dried under shade for 24 h, further dried at 30– 40°C until constant weight was obtained. Size was reduced through grinder. Powdered fruit passed through sieve no. #22 and stored it in air tight container for further use. Extraction of mucilage includes two steps

Step 1: Extraction of mucilage: powdered fruit kept in 500ml of distilled water. Heated with stirred continuous at 60°C for approximately 4h. Concentrated solution has filtrated through muslin. Cloth and cool at 4°C-6°C

Step 2: Isolation of Mucilage: Extracted gum has isolated in acetone. This allows filtration through muslin cloth. Washed with acetone and the mucilage filtrated through muslin cloth. Pressed mucilage was further dried to constant weight at 35–45°C in hot air oven. Hard mucilage cake was grinded and sieved through sieve # 22, stored in desiccators for further used. (Farooq U et al., 2013) and X2) represent the average result of changing 1 factor at a time from its low to high value. The interaction terms (X1X2) show how the response changes when 2 factors are simultaneously changed. The polynomial terms (X1X1 and X2X2) are included to investigate nonlinearity. The results were shown in Table no. 2 (Hardenia S et al., 2016)

Table no. 2: Formulation of different formulation of atenolol fast disintegrating tablet