Formulation Optimization And In Vitro Evaluation of Fexofenadine Orodispersible Films for Rapid Oral Drug Delivery

Formulation of patient?friendly dosage forms that offer rapid onset of action and improved compliance remains a key objective in oral drug delivery, particularly for conditions requiring prompt symptom relief such as allergic rhinitis and chronic urticaria. Fexofenadine hydrochloride, a non?sedating second?generation H1?antihistamine, is widely used for the management of allergic disorders but exhibits relatively low and variable oral bioavailability due to poor aqueous solubility, low permeability and P?glycoprotein–mediated efflux in the intestine. [1] Conventional solid dosage forms of fexofenadine, including film?coated and conventional tablets, are often large, show slow dissolution, and may present swallowing difficulties, especially in pediatric, geriatric and dysphagic patients, which in turn can compromise adherence and therapeutic outcomes. [2] To overcome these drawbacks, various formulation strategies such as solid dispersions, nanostructured lipid carriers, microsponge systems and fast?disintegrating tablets have been explored to enhance dissolution, intestinal absorption and overall bioavailability of fexofenadine. [3]. Among patient?centric dosage forms, orodispersible systems have gained considerable attention because they disintegrate or dissolve rapidly in the oral cavity, generally within seconds, without the need for water, thereby improving convenience and acceptability while providing the potential for faster onset of action. [4] Orodispersible tablets formulations have been shown to achieve very short disintegration times, rapid in vitro drug release and, in some cases, improved in vivo exposure compared with conventional tablets. [5] However, orodispersible tablets may still suffer from friability, risk of sticking in the throat and limited flexibility in dose and shape. Orodispersible films represent an advanced alternative platform, offering ultra?thin, flexible, rapidly dissolving polymeric strips that can be placed on the tongue or buccal mucosa, combining high patient acceptability with accurate dosing and the possibility of pregastric absorption. [6] The present work is therefore aimed at the formulation and systematic evaluation of an orodispersible film of fexofenadine HCl, focusing on critical quality attributes such as mechanical properties, disintegration time, in vitro dissolution in order to establish a robust, patient?oriented dosage form for the effective management of allergic conditions. [7]

MATERILS AND METHOD

Materials

Fexofinadine Hcl was provided as gift sample by Mylan Lab, Mumbai. All other reagents and chemicals utilized in this investigation were of analytical grade.

Method

Preparation Fexofinadine Orodispersible Films

Orodispersible films of fexofenadine were prepared by the solvent casting method using gelatin and carboxymethyl cellulose (CMC) as film-forming polymers. Initially, the accurately weighed quantity of gelatin was soaked in a small volume of distilled water and allowed to swell, followed by heating at 40–50°C with continuous stirring until a clear gelatin solution was obtained. Separately, the required quantity of CMC was dispersed in distilled water under continuous stirring and allowed to hydrate completely to form a uniform viscous solution. Both polymer solutions were then mixed together under continuous magnetic stirring to obtain a homogeneous polymeric blend. In a separate container, fexofenadine was dissolved in ethanol to obtain a clear drug solution, ensuring complete solubilization and uniform drug distribution. The drug solution was then slowly incorporated into the polymeric mixture with continuous stirring to form a uniform drug–polymer dispersion. Subsequently, croscarmellose sodium was added as a superdisintegrant and uniformly dispersed in the mixture, followed by the addition of aspartame as a sweetening agent and citric acid as a saliva-stimulating agent. Glycerol was then added as a plasticizer to impart flexibility and elasticity to the films. The prepared casting solution was then carefully poured into a leveled petri dish of predetermined dimensions to obtain films of uniform thickness. The films were dried at room temperature for 24–48 hours and further in a hot air oven maintained at 40°C until complete solvent evaporation occurred. After drying, the formed films were carefully peeled off from the mould surface and cut into uniform dimensions (2 X 3 cm). The prepared orodispersible films were then packed in aluminium foil and stored in a desiccator until further evaluation. The formulation details of Orodispersible film were given in table 1. [8,9]

Table 1: Composition of Orodispersible Film of Fexofinadine Hcl

EVALUATION OF ORODISPERSIBLE FILMS

Weight Uniformity

Films from each batch were randomly selected and individually weighed using a calibrated digital balance. The mean weight and standard deviation were calculated to assess uniformity and reproducibility of the solvent casting process. [10]

Film Thickness

The thickness of the films was measured at three different points using a digital Vernier caliper, and the average thickness with standard deviation was recorded to ensure uniformity of the casting solution.

Folding Endurance

Folding endurance was determined by repeatedly folding the film at the same point until it broke. The number of folds required to break the film was recorded as the folding endurance value. [11]

Surface pH

The surface pH of the films was determined by placing the film in contact with distilled water for equilibration, followed by measurement using a calibrated pH meter. This test was performed to ensure compatibility with the oral mucosa.

Drug Content Uniformity

Drug content uniformity was determined by dissolving a 2 × 2 cm² film in phosphate buffer pH 6.8, followed by suitable dilution and analysis using a UV–Visible spectrophotometer at 224 nm. The percentage drug content was calculated. [12]

In Vitro Disintegration Time

Disintegration time of Orodispersible film was determined by petri dish method. This technique was carried out on a petri plate. The oral thin film was placed in the centre of a petri dish filled with 10 mL of distilled water. The time taken for the thin layer to disintegrate is measured, and the procedure is done thrice. [13]

In Vitro Dissolution Study

In-vitro dissolution of Fexofinadine Orodispersible films was studied using USP Type 2 dissolution test apparatus, 900 ml phosphate buffer solution pH 6.8 was used as dissolution medium. The stirrer was adjusted to rotate at 50 rpm. The temperature of dissolution medium was maintained at 37±0.5ºC throughout the experiment. Samples of dissolution medium (5ml) were withdrawn by mea8ns of syringe. Solution was filtered with Whatman filter Paper. Sample were withdraw after 1,2,4,6,8 and 10 minute time intervals. The sample ware analyzed for drug release by measuring the absorbance at 224 nm.  The volume withdrawn   at each   time   interval   was   replaced   with   fresh quantity of dissolution   medium. Cumulative percent released of granisetraon was calculated and plotted against time. [14,15]

RESULT AND DISCUSSION

Weight Uniformity of Films

The weight uniformity of the films ranged from 812.45 ± 4.21 mg (F1) to 778.40 ± 4.05 mg (F6). All formulations exhibited minimal weight variation, indicating uniform distribution of polymers, drug, and excipients within the casting solution and consistent solvent evaporation during film formation. The gradual decrease in film weight from F1 to F6 can be attributed to the reduction in gelatin content and the corresponding increase in CMC concentration. Gelatin, being a dense and strong film-forming polymer, contributes significantly to film mass, whereas CMC, though hydrophilic, forms comparatively lighter polymeric matrices. The low standard deviation values reflect good reproducibility and uniform casting, confirming the reliability of the solvent casting method for high-dose drug loading. Result was shown in table 2

Thickness of Films

Film thickness varied from 0.312 ± 0.01 mm (F1) to 0.280 ± 0.01 mm (F6), showing a decreasing trend across formulations. This trend correlates directly with the decreasing gelatin concentration and increasing CMC proportion. Gelatin forms thicker, denser films due to strong intermolecular hydrogen bonding and gel network formation, whereas CMC produces comparatively thinner hydrophilic films. Uniform thickness across all formulations indicates proper leveling of the casting surface and homogeneous distribution of the polymeric solution.

Folding Endurance of Films

Folding endurance values ranged from 298.34 ± 6.12 folds (F1) to 225.32 ± 5.16 folds (F6). The highest folding endurance was observed in gelatin-rich formulations (F1 and F2), indicating excellent flexibility and mechanical strength. This is due to the intrinsic film-forming nature of gelatin and the plasticizing effect of glycerol, which enhances polymer chain mobility and elasticity. As the proportion of CMC increased (F3–F6), folding endurance gradually decreased, reflecting reduced flexibility and increased brittleness. Although CMC improves hydrophilicity and disintegration, it lacks the elastic network-forming capacity of gelatin. However, all formulations still exhibited acceptable mechanical strength for handling, packaging, and patient use, confirming the suitability of the gelatin–CMC polymeric system for ODF development. The results are shown in table 2.

In Vitro Disintegration Time of Films

In-vitro disintegration time showed a significant decreasing trend from 38.25 ± 1.12 seconds (F1) to 20.10 ± 0.88 seconds (F6). This clearly indicates the strong influence of polymer composition and excipient selection on disintegration behavior. Formulations with higher gelatin content exhibited longer disintegration times due to the formation of a stronger, more cohesive gel network. In contrast, increasing CMC concentration enhanced hydrophilicity and water uptake, promoting rapid film hydration and breakup. The presence of croscarmellose sodium, a superdisintegrant, significantly contributed to rapid water absorption and matrix swelling, thereby accelerating disintegration. Additionally, citric acid stimulated saliva production, while glycerol improved wettability and film hydration, further supporting fast disintegration. The average disintegration time of different formulation was shown in figure 1.

Surface pH of Films

The surface pH of the films ranged from 6.72 ± 0.08 (F1) to 6.48 ± 0.07 (F6), remaining within the physiologically acceptable range for the oral cavity (pH 6.5–7.0). This indicates good oral mucosal compatibility and a low risk of irritation. The presence of citric acid as a saliva-stimulating agent and CMC as a hydrophilic polymer slightly influenced the surface pH towards the acidic side, particularly in CMC-rich formulations (F5 and F6).

Table 2. Evaluation Orodispersible  Film of Fexofinadine Hcl

All the values are expressed as mean ± SD, n=3.

Drug Content Uniformity Study of Films

The drug content across all formulations ranged from 97.85 ± 1.02% to 99.55 ± 0.85%, which falls within pharmacopeial acceptance limits (95–105%). This confirms uniform drug distribution within the polymeric matrix and effective solubilization and dispersion of fexofenadine in the ethanol–water solvent system. The results demonstrate the suitability of the formulation method for high-dose drug incorporation without segregation or crystallization.

In Vitro Dissolution Studies

The in-vitro drug release study of the prepared orodispersible films (F1–F6) was carried out to evaluate the effect of polymer composition and formulation variables on the dissolution behavior of fexofenadine from the films. The dissolution profiles demonstrated a rapid and uniform drug release pattern for all formulations, which is a desirable characteristic for orodispersible film dosage forms intended for quick onset of action and improved patient compliance. Among all the formulations, Batch F3 exhibited the highest and most rapid drug release. The superior performance of F3 can be directly correlated with its balanced polymer composition, consisting of gelatin (300 mg) and CMC (150 mg). This ratio provided an optimal combination of film-forming ability, hydrophilicity, mechanical integrity, and rapid hydration, which collectively enhanced the wetting, swelling, and dissolution behavior of the film matrix. The drug release pattern clearly reflected the influence of gelatin–CMC ratio across formulations. Batch F1 and F2, containing higher gelatin content (400–350 mg) and lower CMC levels (50–100 mg), showed comparatively slower drug release. This can be attributed to the dense polymeric network formed by gelatin, which, although excellent for film formation and mechanical strength, tends to retard water penetration and drug diffusion due to its relatively compact gel structure. Batch F5 and F6, containing higher CMC content (250–300 mg) and lower gelatin levels (200–150 mg), showed faster disintegration but comparatively less drug release behavior. Excess CMC increases hydrophilicity and swelling but can compromise matrix integrity, leading to rapid erosion and non-uniform drug diffusion. Formulation F3, with an optimized balance of gelatin and CMC, demonstrated the most efficient release profile, combining rapid hydration due to CMC and structural integrity due to gelatin, This synergy resulted in maximum cumulative drug release in the shortest time, confirming F3 as the optimized batch. The enhanced dissolution performance is also influenced by the functional excipients like Croscarmellose sodium, used as a superdisintegrant in fixed concentration, significantly contributed to rapid film hydration and breakup by wicking and swelling mechanisms, facilitating faster drug diffusion into the dissolution medium. The results for in vitro drug release of orodispersible film was shown in figure 2.

Figure 2: Comparative Dissolution Profile of Fexofinadine Hcl Orodispersible Film (Batch F1 to F6)