Formulation and Performance Evaluation of Mouth-Dissolving Tablets of an Antihypertensive Agent

Oral drug delivery is the most widely used route for drug administration because of its convenience, safety, and better patient compliance. However, conventional tablets and capsules often create swallowing difficulties, particularly in pediatric, geriatric, and dysphagic patients.^1-2 To overcome these limitations, Mouth Dissolving Tablets (MDTs), also known as Orally Disintegrating Tablets (ODTs), have been developed as an advanced oral drug delivery system. These tablets rapidly disintegrate in the mouth without the need for water, providing improved convenience and faster therapeutic action.^3-4 Hypertension is a major cardiovascular disorder that requires long-term treatment and regular medication intake. Poor patient compliance with conventional dosage forms can reduce therapeutic effectiveness. Therefore, formulation of MDTs of antihypertensive agents can improve patient adherence, especially among elderly and bedridden patients who experience difficulty in swallowing. In addition, MDTs provide rapid drug release and enhanced dissolution, which may improve bioavailability and onset of action.^5-8 The formulation of MDTs mainly involves the use of superdisintegrants such as crospovidone, sodium starch glycolate, and croscarmellose sodium, which promote rapid tablet disintegration in saliva. Other excipients including fillers, sweeteners, and flavoring agents are incorporated to improve tablet strength, palatability, and patient acceptability. Among various manufacturing methods, direct compression is commonly preferred because of its simplicity, low cost, and suitability for heat-sensitive drugs.^9-10 Evaluation of MDTs includes pre-compression and post-compression studies such as flow properties, hardness, friability, wetting time, disintegration time, drug content, and dissolution studies. These parameters ensure the quality, stability, and performance of the formulation.¹¹ Hence, the present study focuses on the formulation and performance evaluation of mouth-dissolving tablets of an antihypertensive agent to enhance patient compliance, improve dissolution characteristics, and provide rapid therapeutic effect.

MATERIALS AND METHODS:

MATERIALS:

Finerenone was obtained from S & M Pharmaceuticals and used as the active pharmaceutical ingredient. Microcrystalline cellulose and talc were procured from Loba Chemie Pvt. Ltd., while crospovidone, croscarmellose sodium, and sodium starch glycolate were supplied by BASF India Ltd., Signet Chemical Corporation, and DFE Pharma, respectively. Ethyl cellulose was obtained from Central Drug House (CDH), magnesium stearate from SD Fine Chemicals, and polyethylene glycol 4000 along with methanol from Merck Pvt. Ltd. All materials used were of analytical or pharmaceutical grade.

METHODOLOGY:

Preformulation Studies

Preformulation studies were performed to evaluate the physicochemical properties of Finerenone and its compatibility with excipients used in the formulation of Mouth Dissolving Tablets (MDTs). These studies helped in the selection of suitable excipients and ensured formulation stability and performance.^12-14

Organoleptic Properties

Finerenone was evaluated for its appearance, color, odor, and taste. The drug was found to be a white to pale yellow crystalline powder, odorless, and slightly bitter in taste.

Solubility Studies

Solubility studies were carried out in different solvents and excipients to determine the solubility behavior of Finerenone. The results assisted in selecting suitable formulation components for improving dissolution and bioavailability.

Melting Point Determination

The melting point of Finerenone was determined using a capillary melting point apparatus to assess its purity and thermal stability. A sharp melting point range indicated the purity of the drug sample.¹⁵

FTIR Spectroscopy

Fourier Transform Infrared (FTIR) spectroscopy was performed to evaluate the compatibility of Finerenone with selected excipients. The FTIR spectra of the pure drug and physical mixtures showed no significant changes in characteristic peaks, confirming the absence of drug–excipient interactions.^16-18

Differential Scanning Calorimetry (DSC)

Differential Scanning Calorimetry (DSC) analysis was performed to evaluate the thermal behavior and compatibility of Finerenone with excipients. Approximately 5 mg of sample was sealed in an aluminum pan and heated from 40°C to 300°C at a rate of 10°C/min under a nitrogen atmosphere. The thermograms obtained were used to identify melting behavior and possible drug–excipient interactions.^19-22

Analytical Study

Analytical studies were carried out using UV-Visible spectrophotometry for the estimation and quantification of Finerenone during formulation and evaluation studies. The method was employed for drug content analysis, dissolution studies, and calibration curve development.^23-28

Determination of λmax and Calibration Curve

The λmax of Finerenone was determined in 0.1 N HCl and phosphate buffer pH 6.8 using UV spectrophotometry. The drug showed maximum absorbance at 246 nm in both media. Calibration curves were prepared at different concentrations, and linearity was observed within the selected concentration range.^29-32

Estimation by UV-Visible Spectrophotometry

Finerenone was analyzed using a Shimadzu 1700 UV-Visible spectrophotometer with 1 cm quartz cuvettes. All samples were analyzed in triplicate after baseline correction using respective blank solutions to ensure accuracy and reproducibility.

Preparation of 0.1 N Hydrochloric Acid

0.1 N HCl was prepared by diluting concentrated hydrochloric acid with distilled water to obtain a simulated gastric fluid medium for analytical studies. The solution was freshly prepared before use.

Preparation of Phosphate Buffer pH 6.8

Phosphate buffer pH 6.8 was prepared using potassium dihydrogen phosphate and sodium hydroxide dissolved in distilled water. The pH was adjusted and verified using a calibrated pH meter.

Calibration Curve in 0.1 N HCl

Standard solutions of Finerenone were prepared in 0.1 N HCl at different concentrations, and absorbance was measured at 246 nm. A calibration graph of concentration versus absorbance showed good linearity and was used for quantitative estimation.

Calibration Curve in Phosphate Buffer pH 6.8

Similarly, calibration standards were prepared in phosphate buffer pH 6.8 and analyzed at 246 nm. The calibration curve demonstrated a linear relationship between concentration and absorbance, confirming the suitability of the analytical method.

Formulation Development of Mouth Dissolving Tablets^33-44

Mouth dissolving tablets (MDTs) of Finerenone were developed to improve patient compliance and enhance drug dissolution. Since Finerenone is a poorly water-soluble BCS Class II drug, formulation into MDTs may improve its dissolution rate and provide rapid drug release without the need for water, making it suitable for geriatric and dysphagic patients.

Selection of Excipients

Microcrystalline cellulose (MCC) was used as a filler and binder because of its good compressibility and flow properties. Crospovidone, croscarmellose sodium (CCS), and sodium starch glycolate (SSG) were incorporated as superdisintegrants to promote rapid tablet disintegration. PVP K30 was used as a binder, while aspartame was added as a sweetener to improve palatability. Magnesium stearate and talc were included as lubricant and glidant, respectively, to improve powder flow and compression characteristics.

Method of Preparation

Finerenone MDTs were prepared by the direct compression method due to its simplicity and suitability for moisture-sensitive drugs. All ingredients were passed through a #60 mesh sieve and accurately weighed. The drug and excipients were blended uniformly, followed by the addition of magnesium stearate and talc. The final powder blend was compressed using a rotary tablet compression machine fitted with 8 mm flat-faced punches to obtain tablets with adequate hardness and rapid disintegration properties.

Figure 1: FTIR Spectra of Finerenone (FRN)

Figure 2: DSC Thermogram of Finerenone (FRN) mouth dissolving tablet formulation

Figure 3: λmax of Finerenone (FRN) in 0.1 N HCl

Figure 4: Calibration curve of Finerenone (FRN) in 0.1 N HCl

Figure 5: Hardness of MDT’s

Figure 28: FT-IR Spectra of tablet Formulation

Stability Study

The optimized formulation F4 was subjected to accelerated stability studies at 40°C ± 2°C and 75% RH for 90 days according to ICH guidelines. The formulation showed minimal changes in drug release and hardness during the study period. Drug release remained above 97%, while tablet hardness was maintained between 4.0–4.1 kg/cm², indicating excellent physical and chemical stability of the formulation under accelerated storage conditions.

CONCLUSION:

The present investigation successfully demonstrated the development of mouth dissolving tablets of Finerenone using the direct compression technique. The study confirmed that the selection of suitable superdisintegrants significantly influenced tablet disintegration and drug release behavior. Among all formulations, F4 containing croscarmellose sodium (10 mg) was identified as the optimized formulation due to its superior pre-compression and post-compression characteristics, rapid disintegration, excellent drug release profile, and satisfactory stability. The optimized MDT formulation showed improved dissolution properties, good mechanical strength, acceptable physicochemical characteristics, and enhanced patient-friendly performance. Therefore, the developed Finerenone MDT formulation can be considered a promising oral drug delivery system for improving therapeutic efficacy, patient compliance, and rapid onset of action.

CONFLICT OF INTREST:

The author declares that there is no conflict of interest.

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