Formulation and Evaluation Fast Disintegrating Tablet of Telmisartan

Hypertension, a major risk factor for cardiovascular morbidity and mortality, affects millions globally and requires long-term pharmacological management. Among the various antihypertensive agents, Telmisartan, an angiotensin II receptor blocker (ARB), has garnered significant clinical attention due to its high efficacy, prolonged half-life and favourable safety profile [1]. However, Telmisartan exhibits poor aqueous solubility (Class II drug in BCS classification), resulting in variable and limited oral bioavailability. Traditional oral dosage forms like tablets or capsules often present challenges for geriatric and pediatric patients, especially those suffering from dysphagia, leading to poor adherence and delayed therapeutic response [2]. To address these issues, fast disintegrating tablets (FDTs) have emerged as a novel and patient-friendly drug delivery system. FDTs disintegrate or dissolve rapidly in the saliva within seconds without the need for water, ensuring swift drug release and absorption [3]. This dosage form not only improves patient compliance but also facilitates faster onset of therapeutic action, particularly advantageous in conditions like hypertension where timely blood pressure control is crucial. The formulation of FDTs is technically challenging and demands a careful selection of excipients and optimization of formulation parameters. Super disintegrants play a pivotal role in ensuring rapid disintegration by facilitating swelling, wicking, and de-aggregation mechanisms. The selection of excipients like microcrystalline cellulose (MCC) for its excellent compressibility and disintegration properties, PVP K30 as a binder, citric acid for taste masking, and magnesium stearate and talc as lubricants, significantly influence the final tablet performance. Advanced polymers such as HPMC K30M and Carbopol 940 can also be employed to modify the disintegration profile and provide mechanical strength [4]. Several formulation techniques such as direct compression, sublimation, lyophilization and spray drying have been explored for the development of FDTs. Among these, direct compression remains the most widely used due to its simplicity, cost-effectiveness and scalability. The optimization of critical parameters like tablet hardness, friability, disintegration time and drug content uniformity are crucial for developing a robust formulation [5]. In this context, the present study is designed to formulate and evaluate fast disintegrating tablets of Telmisartan using various super disintegrants and excipients to enhance oral bioavailability, patient compliance and ensure a rapid onset of therapeutic action. The formulation is evaluated through pre-compression and post-compression parameters including hardness, friability, disintegration time, wetting time, drug content and in vitro dissolution studies [6]. The findings of this study aim to establish an effective FDT formulation of Telmisartan suitable for large-scale production and clinical use.

MATERIALS AND METHODS

The active pharmaceutical ingredient, Telmisartan, was obtained from Balaji Drugs Pvt. Ltd., Surat. All other excipients and analytical-grade chemicals including Microcrystalline Cellulose (MCC), Crospovidone, Sodium Saccharine, Magnesium Stearate, Hydroxypropyl Methylcellulose (HPMC) and Lactose were procured from Research-Lab Fine Chem Industries, Mumbai and used without further purification.

Preformulation Studies

Organoleptic Properties: Appearance and color was determined by visual inspection [7].

Melting Point Determination

Thiele's Tube method was used to establish Telmisartan melting point. The glass capillary was sealed from one end and drug was filled into it from another end. Then the capillary tube was tied to the thermometer and placed in the Thiele's tube containing liquid paraffin. The tube was heated and melting point of the drug was determined by observing the temperature on the thermometer when the particles have just started to melt and when all the drug particles were melted [8].

FTIR Studies

Using a Shimadzu IR Affinity-IS (3000), the FTIR spectra of Telmisartan was captured. The drug sample was scanned between 400 and 4000 cm^-1, while in an FTIR sample holder. The spectrum was confirmed by comparing with the IR spectra of Telmisartan [8,9].

Ultraviolet Visible (UV-Vis) Spectrophotometry

Determination of λ-Max of Telmisartan

10 mg of precisely weighed Telmisartan was added to 100 ml of a volumetric flask, and the volume was adjusted with methanol. The stock solution was labelled 100 parts per million (ppm). In a different volumetric flask, 1 ml of the stock solution was extracted, diluted to 10 ml to create a stock solution of 10 ppm, and then analyzed at 200–400 nm. The measured λ-max was 230 nm [10].

Estimation of Calibration Curve in Methanol

The absorbance was measured at λ max using a UV spectrophotometer after dilutions of 2, 4, 6, 8 and 10 ppm were made from the aforesaid stock solution of methanol at 100 ppm [11].

Differential Scanning Calorimetry (DSC)

Differential Scanning Calorimetry (DSC) was employed to investigate any possible physicochemical interactions between Telmisartan and the excipients used in the formulation. The DSC analysis was carried out using a calibrated DSC instrument. Approximately 3–5 mg of pure Telmisartan and physical mixtures (in 1:1 ratio w/w with excipients) were weighed accurately and sealed in standard aluminum pans. The samples were scanned in the temperature range of 30 to 300°C under a nitrogen purge at a flow rate of 50 mL/min, with a heating rate of 10°C/min. An empty aluminum pan was used as a reference. The thermograms were recorded and analyzed for characteristic peaks, melting transitions, and any thermal events that could indicate drug–excipient interactions [11].

Determination of Solubility

It was established that Telmisartan was soluble in both water and methanol [12].

Physical mixture

To assess drug-excipient compatibility, physical mixtures of Telmisartan with individual excipients were prepared in a 1:1 ratio by blending in a mortar and pestle for 10 minutes to ensure homogeneity. The mixtures were then passed through an 80# mesh sieve for uniform particle size and stored in airtight containers placed in a desiccator to prevent moisture uptake. FTIR spectral analysis was conducted using a Shimadzu IR Affinity-IS spectrophotometer, scanning over a range of 400–4000 cm?¹ with a resolution of 4 cm?¹. The FTIR spectrum of pure Telmisartan served as a reference and was compared with those of the physical mixtures to detect any interactions, indicated by shifts, appearance or disappearance of characteristic peaks, or peak broadening. Additionally, the physical mixtures were stored under accelerated stability conditions (40°C/75% RH) for up to two months, and FTIR analysis was repeated at intervals to monitor potential chemical interactions over time [13].

Pre-Compression Evaluation of Powder

Bulk density, tapped density, Carr’s Index, Angle of repose and Hausner's ratio were used to study the flow property of solid formulation.

Bulk density

The precisely weighed powder was poured into a graduated cylinder to measure bulk density. The powder's weight (M) and bulk volume (Vb) were calculated. The following formula was used to get the bulk density:

Bulk density (BD) =  Weight of powderMBulk volume (Vb)

Tapped density

The 100 ml measuring cylinder was filled with the sample powder. A after that a fixed number of taps (100) where applied to the cylinder. Record the final volume and by the following equation the tapped density was calculated.

Tapped Density (TD) = Weight of powderMTapped volume (Vt)

Carr’s index

One of the most crucial metrics for describing the characteristics of powders and granules is Carr's index. From the following equation it can be calculated and category of Carr’s Index is shown in the table 5.4.

Carr’s Index (I) = Tapped densityTD - Bulk density (BD)Tapped density (TD)  

Hausner's ratio

The Hausner's ratio is an index of ease of flow of powder. The    Hausner's ratio less than 1.25 indicates good flow. It is calculated by the formula:

Hausner’s ratio = Tapped DensityBulk Density

Angle of repose

The fixed funnel method was used to calculate the angle of repose. A vertically adjustable funnel was used to pour the mixture until the desired maximum cone height (h) was reached. The following formula was used to determine the angle of repose and measure the heap's radius (r):

Angle of repose θ=tan^-1hr

The radius of the base pile is denoted by r, the height of the pile by h and the angle of repose by θ [14,15].

Preparation of optimized batch by using different super disintegrants

Table 1: Formulations of Fast Dissolving Tablets of Telmisartan

Preparation of Fast Disintegrating Tablets [16]

For each formulation batch (F1 to F4), all ingredients were accurately weighed as per the composition specified in Table 1. Telmisartan, Microcrystalline Cellulose (MCC), Crospovidone, Sodium Saccharine, Hydroxypropyl Methylcellulose (HPMC) and Lactose were passed through sieve no. 40 to ensure uniform particle size and eliminate any lumps or foreign matter. The sifted ingredients were blended thoroughly in a mortar and pestle for 10–15 minutes to achieve a homogeneous mixture. Magnesium Stearate, serving as a lubricant, was separately passed through sieve no. 60 and gently incorporated into the blend. Care was taken to mix the final blend lightly for an additional 2–3 minutes to ensure even distribution of the lubricant, avoiding over-mixing, which could negatively impact tablet quality. The resulting uniform powder blend was then compressed into tablets using a rotary tablet compression machine fitted with 6 mm round flat-faced punches. The compression force was carefully adjusted to obtain tablets with uniform hardness, acceptable friability, and rapid disintegration time. The prepared fast disintegrating tablets were collected and labelled as batches F1 to F4. They were stored in clean, dry, airtight containers until further evaluation, including tests for weight variation, hardness, friability, drug content, disintegration time and in-vitro dissolution.

Optimization of Batch

The optimization of batch for the fast-disintegrating tablets of Telmisartan involved a systematic evaluation of various formulation and process parameters. The drug-to-super disintegrants ratio was carefully adjusted to achieve the desired release profile, ensuring a balance between fast-disintegrating properties and tablet integrity. The concentrations of excipients were fine-tuned to enhance tablet hardness and uniformity, While the levels of other ingredients and magnesium stearate were optimized to improve flowability and prevent sticking during compression. Compression force was standardized to produce tablets with consistent thickness, hardness and friability. In vitro dissolution studies were conducted to evaluate the drug release profile. Powder blend flow properties, including angle of repose and bulk density, were assessed to ensure uniform die filling. Additionally, physical parameters such as weight variation, hardness and friability were evaluated for compliance with pharmacopoeial specifications. Stability studies under accelerated conditions were performed to confirm the formulation’s long-term stability. Formulations combining excipients were also explored to assess their synergistic effects on drug release and overall tablet performance. This comprehensive optimization approach facilitated the development of a robust and reproducible fast-disintegrating tablets formulation for Telmisartan [17,18].

Evaluation of Fast-Disintegrating Tablets [19-22]

Weight variation

Twenty pills of each formulation were weighed in total, and the average was computed. Accurate weight measurements of each tablet were also made and the weight variation was computed.

Hardness

It gauges the amount of force needed to shatter the tablet during testing. For uncoated tablets, a hardness of roughly 0.1-3 kg/cm2 is adequate and the force is expressed in kilograms. A Monsanto hardness tester was used to measure the hardness of ten tablets from each formulation.

Thickness

A digital vernier scale was used to measure the tablet's thickness. mm was used to express thickness.

Friability test

Variability in Digital Programmable Friability A device was used to determine how friable the tablets were. Twenty pills of each formulation were weighed and put in a machine that revolved for four minutes at 25 rpm. The tablets were weighed once more after being dedusted. Weight loss as a percentage was determined.

F = (W int -W fin) /W int ×100

Where,

W int = Initial Weight of tablets before friability

W fin = Final Weight of tablets after friability.

Disintegration time

A one-liter beaker of distilled water was filled with the six-glass tube disintegration apparatus, each holding one tablet. The tablets were positioned so that they remained below the liquid's surface during their upward movement and did not descend more than 2.5 cm from the beaker's bottom and the time it took for the tablet to begin dissolving was recorded.

Drug Content

For the content uniformity test, 20 tablets were weighed and pulverized to a fine powder, a quantity of powder equivalent to 10 mg of Telmisartan was extracted into distilled water and liquid was filtered (0.22 µm membrane filter disc. The Telmisartan content was determined by measuring the absorbance at 296 nm (using UV-vis spectrophotometer, Shimadzu 1800) after appropriate dilution with distilled water. The drug content was determined using standard calibration curve. The mean percent drug content was calculated as an average of three determinations [22].

In Vitro Dissolution

The USP II dissolving testing device was used for the dissolution test. At 50 rpm and 37.7 ºC ± 0.5 ºC, 900 ml of phosphate buffer pH 6.8 was used as the dissolving media. One tablet was used in each test. Aliquots of the dissolution medium (5 ml) were withdrawn at specific time intervals (0, 5, 10, 15, 20 and 30 min.) and replaced immediately with equal volume of fresh medium. The samples were analyzed for drug content by measuring the absorbance at 280 nm. Drug concentration was calculated from the standard calibration curve and expressed as cumulative percent drug dissolved. The release studies were performed in replicates of three [23].

Swelling behavior of tablet

The tablet calculated the % weight gain to determine the degree of edema. Every formulation's swelling behavior was examined. Each formulation's single tablet was stored in a Petri dish filled with phosphate buffer at a pH of 6.8. The tablet was taken out, soaked in tissue paper, and weighed after two minutes. The pill weights were then recorded every two minutes and this process was carried out until the end of ten minutes. A formula was used to determine the tablet's % weight gain;

S.I. = {(Mt-Mo) / Mo} X 100,

Where, S.I. = swelling index, Mt = weight of tablet at time (in sec) and Mo = weight of tablet at time t =0.

Stability study

The drug's manufactured fast disintegrating tablets were wrapped in an aluminum strip and placed in a humidity chamber for 30 and 60 days at 40 ± 2°C and 75 ± 5% relative humidity for accelerated stability tests. After 30 and 60 days, the sample was removed since there was a noticeable change in the way the tablets looked and released the medicine. Disintegration time, wetting time, and batch optimization are all noted in the CPR profile of stability investigations [24].

RESULTS AND DISCUSSION

Preformulation Studies

Organoleptic Analysis: Telmisartan was evaluated for its organoleptic properties like appearance, colour, odour and nature by visual inspection.

Table 2: Organoleptic Analysis