Formulation and Evaluation of Mouth Dissolving Film of Irbesartan

Mohd Bilal Sufi; Mohammad Tabish*; Rajlaxmi Deolekara

Department of Pharmaceutics, New Montfort Institute of Pharmacy, Ashti, Dist;Wardha, (M.S) 442202

*Correspondence: mohammadtabish062@gmail.com

DOI: https://doi.org/10.71431/IJRPAS.2026.5709        

INTRODUCTION

Oral route continues to be the most widely accepted method of systemic drug delivery since it is a safe, convenient and cost-effective route, while supporting self-administration for many doses, chronic treatment and flexible dosing regimens.[1-2] Solid oral dosage forms, such as tablets and capsules, dominate due to accurate dosing, good stability and easy manufacturing but their performance is extremely sensitive to both drug solubility and gastrointestinal physiology. [1,3] A substantial proportion of new chemical entities fall into Biopharmaceutics Classification System (BCS) classes II and IV, characterized by poor aqueous solubility and limited permeability, leading to dissolution-limited absorption and highly variable oral bioavailability.[2-4] Such challenges have triggered abundant investigations on novel oral delivery approaches such as solid dispersions, lipid-based systems, nanocrystals and innovative dosage forms to bypass the barriers imposed by dissolution and first-pass. [1,5-6]

Despite their advantages, conventional tablets and capsules present clinically relevant limitations in specific patient populations, particularly where swallowing difficulties (dysphagia), nausea, or impaired coordination compromise the ability to take solid oral medications reliably.[7,8] The combination of large tablet size, high surface roughness and need to drink enough fluid also increase swallowing difficulties, while most regulatory assessments have pointed the oversized solid supplements and drugs as causing significant pill dysphagia and aspiration in elder population. [7, 9] Inadequate swallowability are partly blamed for poor adherence or omission of dosing or incorrect manipulation of tablets (crushed or split), which can affect drug release properties and therapeutic effect. And hence, patient-friendly oral systems are highly sought-after for their rapid action without compromising .​[7-8] Consequently, there is a clear need for patient‑friendly oral systems that provide rapid action, minimize swallowing burden, and maintain robust quality attributes suitable for diverse age groups and clinical settings.[10-11]

Mouth dissolving films (MDFs)—also known as oral thin films (OTFs) or oral wafers—are a new sophisticated oral solid dosage form designed to disintegrate and dissolve rapidly in the saliva upon placement on the tongue or buccal mucosa without water or chewing. [10, 12] These flexible slender polymeric strips are generally formed of hygroscopic film‑forming polymers, plasticizers, sweeteners, saliva stimulants, surfactants, flavours and taste‑masking agents when appropriate taste‑masking agents, collectively engineered to provide rapid hydration, structural integrity, and acceptable organoleptic properties.[10, 13-14] Widely film formers can be derived from hydroxypropyl methylcellulose (HPMC), pullulan, sodium alginate, polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP) maltodextrin and other natural or synthetic hydrocolloids suitable for achieving appropriate viscosity, mechanical strength and dissolution performance. [10, 13-15]

Compared with conventional tablets and even orally disintegrating tablets (ODTs), MDFs offer several distinct advantages, including faster disintegration, avoidance of the swallowing act, no requirement for concomitant water intake, and the possibility of partial pre‑gastric absorption via the oral mucosa. [10, 12, 16] These features result in rapid onset of action, greater patient convenience and compliance, and specific utility for paediatric, geriatric and bedridden patients; as well as other populations including those who are afraid to swallow or suffer from motion sickness. [10-11, 16] From a formulation perspective, critical performance attributes of MDFs include disintegration time, mechanical strength (tensile strength, folding endurance, percent elongation), drug loading capacity, surface pH, and palatability, which together determine ease of handling, dosing uniformity, and patient acceptability. [10, 14, 17-18] The rapid disintegration behaviour must be balanced against sufficient mechanical robustness to withstand processing, packaging, and administration without cracking or sticking. [18-10]

The technology of oral thin film has transformed from simple fast-dissolving systems in the recent years to current smart oral wafers with nanocarrier, mucoadhesive polymers, and designed release profiles for localized or systemic therapy. MDFs for antiemetics, proton pump inhibitors, local anaesthetics and other low-dose drugs have been successfully developed with low levels of various HPMC, PVA, sodium alginate and plasticizer combinations showing quick disintegration (generally within 15–30 seconds), high drug dissolution (>80–90% in minutes) and good mechanical properties using optimized HPMC, PVA, sodium alginate, and plasticizer combinations prepared by solvent casting.[14-16] These advances underscore the versatility of MDFs as a promising platform for low- to moderate-dose drugs requiring rapid onset of action and improved patient-centric delivery. [10-11]

Irbesartan, an angiotensin II receptor blocker (ARB), is a well-accepted antihypertensive drug that specifically antagonizes the AT₁ receptor of the renin–angiotensin–aldosterone system. Irbesartan blocks the action of an AT1 receptor; therefore vasoconstriction, aldosterone secretion and sodium retention are decreased resulting in lowering BP as well as conferring cardioprotective and renoprotective effects. [19-20] Clinically, irbesartan is indicated for the treatment of essential hypertension and has been shown to have an impressive efficacy in delaying the progress of diabetic nephropathy and exhibiting an effect on albuminuria reduction. in patients with type 2 diabetes and chronic kidney disease.[20-22]

Pharmacokinetic studies show that the oral bioavailability of irbesartan is high (approximately 60–80%), with an elimination half‑life of approximately 11–15 hours, permitting once‑daily dosing. [21, 23] Highly protein‑bound, with a large apparent volume of distribution and multiple phases in its absorption (two plasma concentration peaks) due to pH-dependent dissolution, gastric emptying dynamics and potential enterohepatic recirculation. [23] Irbesartan belongs to the BCS class II drug and is poorly water‑soluble, its dissolution‑limited absorption causes variability in oral exposure and requires additional formulation strategies to promote solubilization in gastrointestinal fluids. [24-26] Consistent with this classification, multiple studies have focused on improving irbesartan’s dissolution and bioavailability using nanocrystalline suspensions, self‑microemulsifying drug delivery systems (SMEDDS), transdermal patches, and salt formation approaches. [25-28]

Conventional irbesartan tablets are dependent on dissolution of a poorly soluble drug in the gastrointestinal tract, which can be suboptimal in patients with altered gastric conditions or who take co‑medications that affect pH or have rapid transit and still represent a challenge for older hypertensive patients with dysphagia or frailty. [7,21] Although markedly improved dissolution and intestinal absorption have been observed for such systems, these are typically achieved using formulations requiring hydrophilic encapsulation or specialized dosage forms and as an approach, nanocrystal-based suspensions and SMEDDS do not alleviate the swallowing burden associated with solid tablets. [27-28] Transdermal patches, while bypassing first‑pass metabolism and solubility constraints, involve dermal application and may be limited by skin irritation, adhesion issues, and patient preference. Thus, there remains a need for an oral dosage form that simultaneously improves convenience for dysphagic patients and has the potential to enhance dissolution and early absorption of irbesartan.

For a BCS class II, poorly water‐soluble, drug like irbesartan, a rational patient‐centric approach for formulation is to incorporate the drug in a thin dispersible matrix of the hydrophilic film-forming polymers, such as they would provide rapid disintegration in the oral cavity, eliminating the requirement to swallow a conventional tablet and therefore also reducing the risk of aspiration and improving the adherence in geriatric and bedridden patients, while positioning the drug in close contact with the mucosal surfaces, which, in case of irbesartan, may help to achieve partial pre‐gastric absorption and reduce first‐pass effect. [11, 21] The use of hydrophilic film-forming polymers in an MDF increases the wetted surface area of the drug and may facilitate faster dissolution, while positioning the drug in close contact with mucosal surfaces, potentially enabling partial pre‑gastric absorption and reduction of first‑pass effects. [10, 13, 29] For a BCS class II, poorly water‑soluble drug such as irbesartan, incorporation into a thin, rapidly hydrating polymeric matrix represents a complementary strategy to existing solubility‑enhancement approaches, aiming to improve early dissolution and onset of antihypertensive action. [25, 27-28]

Due to the solubility and absorption challenges of irbesartan, formulation optimization of MDFs is essential to achieve uniform drug content, robust film properties and improved dissolution properties over conventional tablets as has been demonstrated in other irbesartan MDF systems by design of experiments studies on formulation parameters such as the type and concentration of film forming polymer, plasticizer, surfactant and saliva stimulant, and the processing parameters for the solvent casting method. [15, 17-18, 31]

Hydrophilic polymers such as HPMC, pullulan, sodium alginate, PVA, PVP and maltodextrin are extensively accepted film forming agents used in fast dissolving oral films since it is well known that they form uniform flexible matrices with rapid hydration while keeping mechanical stability. [10, 13-15] Natural polysaccharides such as pectin, gelatin and chitosan have also been investigated to improve biocompatibility and mouth feel, while mixtures of natural and synthetic polymers showed promising modifications on the mechanical properties and disintegration profiles. [13-15] Reducing brittleness and increasing flexibility are achieved by the incorporation of plasticizers, for example polyethylene glycol (PEG 400), glycerol, and propylene glycol, with several studies demonstrating that PEG 400 and glycerol play an important role on tensile strength, folding endurance, and disintegration time of MDFs. [16-18, 31-32] Additional excipients, including saliva stimulants (e.g., citric acid), sweeteners (e.g., mannitol, sucralose), surfactants, and flavoring agents, are selected to improve wetting, taste masking, and patient acceptance without compromising film integrity. [10-11, 16, 32]

Among the available manufacturing techniques, solvent casting is generally regarded as the most common and favoured avenue for preparing MDFs, while providing a high degree of control over film thickness, homogeneity and surface appearance; producing smooth and homogeneous glossy MDF with reproducible mechanical properties. [10, 12, 14-15] In this process, the drug and excipients are either dissolved or dispersed, this solution is cast onto an inert support and dried under controlled conditions to create a stable film that is subsequently cut into unit doses thus enabling accurate content uniformity of medicament. [10, 12, 15]. Comprehensive evaluation of MDFs typically involves measurement of thickness, weight variation, folding endurance, tensile strength, percentage elongation, surface pH, drug content uniformity, in vitro disintegration time, dissolution profile, moisture uptake and loss, and stability under accelerated conditions. [10, 14, 17-18, 30-32]. These parameters directly relate to product quality and clinical performance, as they assure dose uniformity, mechanical robustness during handling phase, rapid disintegration and drug release in the oral cavity and maintenance of physical & chemical stability over whole shelf life. [10, 15, 17, 30]

In this context, the aim of the present work is to develop a solvent casted mouth dissolving film of irbesartan using suitable hydrophilic film-forming polymers and plasticizers along with evaluation of the films with physicochemical properties, mechanical strength and in vitro disintegration and dissolution properties for optimizing formulation for patient compliance and oral drug delivery in vulnerable patients with swallowing difficulties, where swallowing is one of the limitations in terms of solubility in water which affects the oral bioavailability of the drug. [10-11,21]

MATERIALS AND METHODOLOGY

Materials

Irbesartan was purchased as gift sample from Swapnroop Drugs and Pharmaceuticals, Aurangabad, India. Hydroxypropyl methylcellulose (HPMC) E5, HPMC E15, HPMC K15M, citric acid, polysorbate 80, methanol, saturated potassium chloride solution, anhydrous calcium chloride, and pH 6.8 phosphate buffer were procured from Research Lab Fine Chem Industries, Mumbai, India. Pullulan was obtained from Simpson, while polyethylene glycol (PEG 400) was purchased from Thermosil Lab Fine Chem. Peppermint flavour was also procured from Research Lab Fine Chem Industries, Mumbai, India. All chemicals and reagents used in the study were of analytical grade and were used as received without further purification..

Instrumentation:

he study utilized a Shimadzu UV-1800 UV–Visible spectrophotometer for spectrophotometric analysis and a Bruker Fourier Transform Infrared (FT-IR) spectrophotometer equipped with an Attenuated Total Reflectance (ATR) accessory for compatibility studies. An Analytical Balance (Shimadzu TX4231, Mumbai) was used for accurate weighing of materials. Mixing of polymeric solutions was carried out using a LabLine magnetic stirrer, while film drying was performed in a REMI controlled drying chamber. Film thickness was measured using a Vernier calliper, and samples were stored in a Borosil desiccator under controlled conditions. In vitro dissolution studies were conducted using an Electro Lab TDT-08L USP Dissolution Apparatus Type II, and a LabLine sonicator was employed for degassing and sample preparation.

Determination of Absorption Spectra (λmax)

A UV–Visible spectrophotometer was used to obtain the wavelength of maximum absorption (λmax) of Irbesartan. Irbesartan stock solution was prepared by dissolving an accurate weighed amount of the drug in methanol at a concentration of 100 μg/ mL. The solution was sonicated for 10 minutes in order to achieve a complete dissolution and filtered in Whatman filter paper No. 1. An aliquot of stock solution was diluted with methanol to get the working solution concentration of 10 μg/mL. Scanning of the solution was carried out over a range of wavelengths from 200 to 400 nm with methanol as a blank.[33]

Preparation of Calibration Curve

The standard solution was prepared in methanol in order to have 100 μg/mL of Irbesartan. A set of working standard solutions with concentration 5, 10, 15, 20 and 25 μg/mL was made by appropriate dilution of the above stock solution with methanol. A UV–Visible spectrophotometers was used to determine the absorbance each of the solutions using methanol as a blank. A calibration curve was built by plotting graph of absorbance vs. concentration, and regression equation and R² (correlation coefficient) was computed to study the linear range of the analytical method. [34]

Fourier Transform Infrared (FTIR) Spectroscopy

Fourier Transform Infrared (FTIR) spectroscopy was used to identify the characteristics functional groups in Irbesartan and to establish its chemical structure. FTIR spectrum of the pure drug was recorded using FTIR spectrophotometer in the spectral range of 4000 – 400 cm⁻¹ by the Attenuated Total Reflectance (ATR) technique. The spectrum of a small amount of the drug sample was then taken directly on the ATR crystal and the spectrum was recorded after a suitable background correction. The obtained spectra was compared with that of standard Irbesartan to ensure the existence of the characteristic functional groups.[35]

Drug–Excipient Compatibility Study

FTIR spectroscopy was used to evaluate the compatibility of the selected excipients with Irbesartan. The excipients were gently mixed in a mortar to obtain a physical mixture with Irbesartan in ratio 1:1. FTIR spectrum of the physical mixture was obtained under the same instrumental conditions within the wavelength range of 4000 – 400 cm⁻¹. The spectrum obtained was compared with the pure drug spectrum to see any shift in peaks, disappearance or appearance of new peaks. There was negligible spectral change not affecting any of the formulation excipients, reflecting good compatibility between Irbesartan and these excipients.[36]

Formulation procedure of irbesartan mouth-dissolving films:

Irbesartan mouth-dissolving films were formulated using solvent casting method with the different film-forming polymers and polymer concentrations as depicted in the formulation table 01. For each batch (F1–F12) preparation, the required quantity of polymer (HPMC E5, HPMC E15, Pullulan, or HPMC K15M), was weighed accurately and mixed slowly with the required quantity of water under continuous magnetic stirring. The polymer dispersion was then allowed to hydrate completely during a period of 4–6 hours at room temperature and a clear homogeneous polymeric solution was obtained. Irbesartan was weighed correctly and dissolved in a specific amount of methanol ensuring complete solubilization. Citric acid, a saliva-stimulant agent, was added to this drug solution and dissolved. A surfactant, Polysorbate 80, was then added for enhancing drug dispersion in the polymeric matrix followed by PEG 400 as a plasticizer to impart flexibility to the film and to avoid brittleness. Peppermint flavour was also employed to increase palatability. The drug solution was mixed with the hydrated polymer solution gradually under constant stirring to get a homogenous mixture of drugs and polymer. The final volume was adjusted with purified water and methanol (q.s.) to obtain a smooth and bubble-free casting solution. The resulting solution was deaerated by keeping it undisturbed for a short duration to remove the trapped air bubbles. The prepared casting solution was poured uniformly onto a petri plate and uniformly spread to ensure uniform thickness. The films were allowed to dry in a controlled drying chamber, then on room temperature, until all the solvents had evaporated. The dried films were then gently peeled off and cut into homogenous strips each containing required dose of Irbesartan, yielding 16 films per batch. [37]

Table 01. Formulation Table

Evaluation of Oral Films

Film Thickness

The thickness of the prepared oral films were measured with a calibrated digital micrometre screw gauge. To minimize film-to-film variation, three measurements were made—at the middle and at the two side edges—which were opposite—of each film strip. The average thickness and standard deviation were determined and reported in millimetres (mm). Uniform film thickness is of utmost importance for uniform drug distribution, mechanical strength and reproducible drug release.[38]

Surface pH

Oral films were tested for surface pH to be sure their surface characteristics were appropriate for the buccal mucosa. All films were immersed and allowed to swell for about 30 minutes at room temperature in distilled water in a Petri dish. The pH of the surface was determined by carefully setting the pH electrode probe on the swollen surface of a film onto a calibrated digital pH meter. Each measurement was made 3 times and data averaged to get a central tendency value. The surface pH of the films in the vicinity of neutral was deemed to be suitable to be taken orally without causing oral irritation.

Moisture Content

Oral films were prepared of several moisture contents and the strips were accurately cut and placed in a desiccator containing anhydrous calcium chloride for 24 hours to determine the percentage moisture content of the films. The dried films were then reweighed and percentage loss of moisture calculated. The determination was repeated three times and the results were expressed as Mean ± standard deviation.[39]

Moisture Uptake

The aim of moisture uptake study is to assess the degree of hygroscopic property of prepared oral films. The dried film strips were previously accurately weighed and stored in a desiccator with relative humidity near 75% using saturated sodium chloride solution. Films were kept for 24 hours then they were taken out and reweighed. The percentage moisture uptake was used as a percentage increase in weight. The tests were conducted three times and results reported as the mean ± SD.[40]

Drug Content Uniformity

The drug content uniformity was obtained by careful weights of each film strip with the same amount of Irbesartan and dissolving them accordingly in 100 mL of methanol. The solutions were sonicated for 15 minutes to ensure complete extraction of the drug to remove it from the filter paper, which was followed by Whatman filter paper no.1 filtration. appropriate dilutions were made and the absorbance at 246 nm was scanned using a UV–visible spectrophotometer machine. The drug content was determined by using the calibration curve and expressed as a percent of the labelled amount.[41]

Folding Endurance

The strength and flexibility of the oral films was assessed by measuring their folding endurance. Each of the film strips was folded many times, starting from the same folding point, by hand until it fractured or cracked visibly. The folding endurance was defined as the number of folds needed to break the film. The experiments were conducted with three different film strips of each formulation and the mean value was reported.[42]

Disintegration Time

For the determination of the disintegrating time of the oral films, USP disintegration test apparatus was used, the water is used as the disintegration medium and the temperature of water is maintained at 37 ± 0.5°C. Individual film strips were carefully introduced into the medium and the time taken for complete disintegration (free from any visible sign) was recorded with the help of a digital stopwatch. The process and determination was repeated three times and the average value of disintegration time was presented in seconds.[43]

In Vitro Drug Release Study

The in vitro drug release study was conducted in USP Type II (Paddle) dissolution apparatus. The phosphate buffer solution (pH 6.8) at 37 ± 0.5°C was used as the dissolution medium at 50 rpm paddle speed. The oral films were introduced into the dissolution vessel and 5 mL aliquots were removed after the specific time intervals of 30, 60, 120, 240, 360, 480 and 600 seconds. A same volume of fresh dissolution medium at the same temperature was added after each sampling for maintaining the sink condition. The filtered samples (with filtered Whatman filter paper No. 1) were absorbance measured with the UV–Visible spectrophotometer at 246 nm. The drug release profile was measured from the calibration curve and represented as a cumulative percentage drug release to determine the drug release behaviour of the prepared oral films.[43]

RESULT AND DISCUSSION:

Preformulation studies:

Determination of Absorption Spectra:

UV-Visible Spectroscopy was used to characterize the absorption spectra of Irbesartan, by acquiring the absorbance spectrum of the standard drug solution in methanol as a solvent with UV-Visible Spectrophotometers in the range of 200 nm to 400 nm. The drug exhibited sharp and well-defined absorption maximum (λmax) at 246 nm as shown in Fig. 01. The unique absorption peak at 246 nm further established the appropriateness of this wavelength for quantitative determination of Irbesartan and subsequently led to the selection of this wavelength for all further analytical investigations.

Fig 01. Absorption spectra of Irbesartan

Calibration Curve:

Standard solutions of different concentrations were prepared and the corresponding absorbance of each solution measured at λmax to obtain the calibration curve of Irbesartan. The regression equation obtained for the range studied was y = 0.035936x − 0.02254 with a correlation coefficient (R² = 0.9921) indicating that the results obtained were linear. The high correlation coefficient showed that there was excellent linearity and hence the developed analytical method was well suited for the quantitative estimation of Irbesartan in the formulations.

Fig 02. Calibration Curve for Irbesartan

FTIR Analysis

FTIR spectrum of the pure Irbesartan showed all the peaks of the characteristic functional groups of the drug confirming its identity and purity. The peak resulted obtained in the study correspond with the reported standard spectrum which shows that the drug remained chemically intact throughout the study.

Drug–Excipient Compatibility Study

The FTIR spectra of the formulated mixture with the excipients of the formulation and pure Irbesartan were compared. No characteristic peak was observed to shift, disappear or appear in the characteristic absorption bands. It was confirmed that there was no interaction between the selected excipients and Irbesartan, meaning that the components of the formulation were compatible and suitable for being made into oral films.

EVALUATION PARAMETERS:

Film Thickness (mm)

The thickness of the prepared oral films was found to be 0.07 ± 0.01 mm to 0.18 ± 0.01 mm. The thickness of most of the formulations was also found to be uniform, showing uniformity of casting and uniformity in the polymeric matrix. The minor differences noted with the various formulations were believed to be a result of differences in the polymer concentration and composition. To achieve the dose accuracy and reproducible drug release the films should be uniform in thickness.

Fig 03. FTIR of pure Irbesartan

Fig 04. FTIR of Irbesartan with excipient mixture (Physical mixture 1:1)

Surface pH

The surface pH of all the formulations was between 6.6 ± 0.1 and 6.9 ± 0.1 and this is within physiological pH of oral cavity. This means that the prepared films will likely not be irritating or cause discomfort in the mouth during film administration. The almost neutral surface pH also illustrates the relationship between the excipients chosen with respect to their suitability for oral film formulations.

Moisture Content (%)

The moisture content of the formulations varied from 2.25 ± 0.12% to 4.25 ± 0.17%. The results showed that moisture in the formulations decreased with the decrease in polymer concentration and conversely, the films with higher polymer concentrations had comparatively higher moisture contents. The obtained values show that the film is dried without any significant damage to its flexibility, and has not become brittle.

Moisture Uptake (%):

The percentage moisture uptake ranged between 4.37 ± 0.17% and 7.77 ± 0.24%. Films containing higher amounts of hydrophilic polymers absorbed relatively more atmospheric moisture due to the presence of hydroxyl-containing polymer chains. However, all formulations exhibited acceptable moisture uptake values, indicating satisfactory stability under normal storage conditions.

Drug Content Uniformity (%):

All formulations were found contain 98.1 ± 1.2% to 99.6 ± 1.1% of the labelled amount of Irbesartan by content analysis of the drug. The low difference between the formulations indicated good homogeneity among the formulations, which also suggested uniform distribution of the drug within the polymeric matrix. Pharmacopeial specifications were fulfilled with all the values, which means, there was proper mixing and casting of the formulation.

Folding Endurance (times):

These showed that the folding endurance values ranged from 112 ± 6 to 300 ± 15 folds. The higher the folding endurances the greater the mechanical strength and bends of the films. The formulation with optimized polymer concentration also had better folding endurance properties because of the better film forming properties; on the other hand, thinner formulations had comparatively lower folding endurance properties.

Disintegration Time (seconds):

The disintegration time of prepared oral films was 20 ± 2 to 55 ± 6 seconds. The formulations with lower polymer ratios had longer disintegration times (48 ± 2 seconds to 92 ± 8 seconds) while formulation F4 with lower amount of polymer had very short disintegration time (20 ± 2 seconds), which means that the other formulations did not disintegrate into the film as fast and hydrated comparatively longer time. All the formulations were found to be disintegrating the desired time for fast dissolving oral films.

Table 02. Evaluation  parameters

In Vitro Drug Release:

The drug release study in vitro showed excellent and quick release of Irbesartan from all Oral films prepared. Overall, cumulative drug release increased linearly as a function of time, ranging from 91.5% to 99.6% at the end of 600s, which was an overall good release profile of immediate release. Among all formulations, F4 exhibited the highest cumulative drug release (99.6%), followed by F7 (99.1%), F8 (98.8%), and F1 (98.5%). This improved release of the formulation F4 could be explained by its optimised polymer composition that allowed rapid hydration, quicker film disintegration, and facilitating drug diffusion in the dissolution medium. Formulations F10, F11 and F12 seemed to have comparatively slower release of drug due to forming dense polymeric matrix, which reduced the entry of water and diffusion of drug. The release profile differences between the formulations enclose that the kind and strength of the polymers had a significant effect on the release behaviour of the drug. In spite of all the formulations showed acceptable drug release, F4 was found to be optimized formulation as obtained the highest drug release, minimum disintegration time along with good physical property concerning drug content and desirable mechanical characteristics so that it is suitable for immediate release oral film (IR) delivery of irbesartan.

Table 03. In vitro drug release

Determination of optimized batch:

Batch F4 containing 500 mg of HPMC E15 was identified as the optimized Irbesartan mouth-dissolving film based on its superior physicochemical and performance characteristics. The formulation exhibited an optimal thickness (0.15 ± 0.01 mm), surface pH (6.9 ± 0.1), high folding endurance (265 ± 11), moderate moisture content (2.45 ± 0.12%), controlled moisture uptake (4.77 ± 0.18%), and excellent drug content uniformity (99.6 ± 1.1%). F4 also showed the shortest disintegration time (20 ± 2 s), attributed to the balanced hydrophilicity and moderate viscosity of HPMC E15. Furthermore, it achieved rapid drug release, with 42.5%, 79.6%, and 99.6% cumulative release at 30, 120, and 600 seconds, respectively, making it the most suitable formulation for rapid oral drug delivery.

Fig 05. In–vitro drug release

CONCLUSION:

Irbesartan mouth-dissolving films were successfully formulated using different grades and concentrations of polymers by the solvent casting method. Preformulation studies confirmed the suitability of the drug for formulation, with FTIR analysis demonstrating compatibility between Irbesartan and the selected excipients. All prepared films exhibited satisfactory physicochemical characteristics, including uniform thickness, acceptable moisture content and uptake, excellent drug content uniformity, adequate mechanical strength, and rapid disintegration. The in-vitro drug release profile was influenced by the polymer type and concentration, with HPMC E15-based films showing the most favourable performance. Among all formulations, batch F4 containing 500 mg of HPMC E15 demonstrated the optimum balance of film properties, exhibiting a disintegration time of 20 ± 2 s and 99.6% cumulative drug release within 600 s. These findings indicate that the optimized formulation provides rapid drug release, good mechanical integrity, and satisfactory stability, making it a promising alternative to conventional oral dosage forms for improving patient compliance and achieving rapid therapeutic action.

REFERENCES:

1.        Kshirasagar N, Kotha RR, Rajigari S, Malvey S. The Role of Nanotechnology in the Pharmaceutical Industry: Innovations in Diagnostics and Targeted Drug Delivery. Int J Res Pharm Sci. 2026; 17(2):1-11.

2.        Bindhani S, Mohapatra U, Mohapatra S, Kar RK. Enhancement of Solubility and Dissolution Rate of Poorly Soluble Drug Nifedipine by Solid Sedds. Int J Drug Deliv Technol. 2020; 10(1):9-15.

3.        Kohli K, Chopra S, Dhar D, Arora S, Khar RK. Self emulsifying drug delivery systems: an approach to enhance oral bioavailability. Drug Discov Today. 2009; 15:958-965.

4.        Kovačević AB. Lipid nanocarriers for delivery of poorly soluble and poorly permeable drugs. In: Shegokar R, editor. Nanopharmaceuticals. Amsterdam: Elsevier; 2020. p. 151-174.

5.        Martin B, Garrait G, Beyssac E, et al. Organogel Nanoparticles as a New Way to Improve Oral Bioavailability of Poorly Soluble Compounds. Pharm Res. 2020; 37:92.

6.        Kenechukwu FC, Dias ML, Ricci-Júnior E. Biodegradable nanoparticles from prosopisylated cellulose as a platform for enhanced oral bioavailability of poorly water-soluble drugs. Carbohydr Polym. 2021; 256:117492.

7.        Jotz GP, Carrara-de-Angelis E. Disfagia: abordagem clínica e cirúrgica: criança, adulto e idoso. Rio de Janeiro: Elsevier; 2017.

8.        Geller AI, Shehab N, Weidle NJ, et al. Emergency department visits for adverse events related to dietary supplements. N Engl J Med. 2015; 373:1531-40.

9.        Manoj Kumar G, Hemalatha N, Sravani T, Julisha M, Mustaq SJH, Saketi CS, et al. Smart Oral Thin Films: Preparation Technologies and Evaluation Insights. Int J Drug Deliv Technol. 2026; 16(46s):356-362.

10.    Nandakumar A, Shivakumar HN, Lakshmi Priya NS, Yashwanth S. Oral Wafer Technology: Revolutionizing Drug Delivery for Enhanced Patient Compliance and Bioavailability of Specific Low Dose Drug Categories. J Adv Med Pharm Sci. 2025; 27(5):8-32.

11.    Pawar R, Sharma R, Sharma P, Darwhekar G. A Review on Mouth Dissolving Film. J Drug Deliv Ther. 2019 Nov 15; 9(6):206-10.

12.    Arora L, Chakraborty T. A Review on New Generation Orodispersible Films and its Novel Approaches. Indo Am J Pharm Res. 2017; 7(1):7451-7470.

13.    K S, Konatham TKR. DESIGN, COMPARISON, AND EVALUATION OF LIDOCAINE HYDROCHLORIDE ORAL THIN FILMS USING NATURAL AND SYNTHETIC POLYMERS. Int J Pharm Drug Anal. 2026 Feb; 14(1):20-24.

14.    Gupta A, Kumar V, Goyal AK, Kumawat B, Agarwal J. Formulation And Evaluation Of Oral Thin Film Of Esomeprazole And Domperidone Using 3^2 Factorial Design. Int J Drug Deliv Technol. 2026; 16(26s):171-181.

15.    Design And Evaluation Of HPMC-Based Diclofenac Sodium Transdermal Patches: Application Of 3^2 Factorial Design For Optimization. Int J Environ Sci. 2025; 1421-1432.

16.    Baviskar AD, et al. FORMULATION OPTIMIZATION AND EVALUATION OF MOUTH DISSOLVING FILM OF APREPITANT. Asian J Pharm Clin Res. 2019 Sep; 12(9):154-63.

17.    Maddela S, Nalluri BN. DEVELOPMENT OF ZOLMITRIPTAN MOUTH DISSOLVING FILMS: FORMULATION VARIABLES, MECHANICAL PROPERTIES, AND IN VITRO DRUG RELEASE STUDIES. Asian J Pharm Clin Res. 2019 Apr; 12(4):273-9.

18.    Patil P, Shrivastava SK. Fast Dissolving Oral Films: An Innovative Drug Delivery System. Int J Sci Res. 2014; 3(7):2088-2093.

19.    Devaraj H, Venkatachalam S, Radhakrishnan A. A Review on Formulation of Oral Dissolving Film. J Chem Pharm Res. 2018; 10(4):151-159.

20.    Hassan MM, Bilal R, Tehseen R, Jamshaid M, Bashir I, Zulfiqar S. Oral Films: A Comprehensive Review. Int Pharm J. 2016; 5(12):111-117.

21.    Nio Y, Ookawara M, Yamasaki M, et al. Ameliorative effect of phosphodiesterase 4 and 5 inhibitors in deoxycorticosterone acetate-salt hypertensive uni-nephrectomized KKAy mice. FASEB J. 2020; 34:14997-15014.

22.    Agrawal AG, Kumar A, Gide PS. Self-emulsifying drug delivery system for enhanced solubility and dissolution of glipizide. Colloids Surf B Biointerfaces. 2015; 126:553-560.

23.    Singh AK, Chaurasiya A, Awasthi A, Mishra G, Asati D, Khar RK, et al. Oral bioavailability enhancement of exemestane from self-microemulsifying drug delivery system (SMEDDS). AAPS PharmSciTech. 2009; 10:906-916.

24.    Wang J, Wu C, Zhang M, Hou L, Chen W, Jing D, et al. Seven New Irbesartan Salts: Significantly Improved Dissolution, Excellent Hygrothermal Stability, and Characteristic Supramolecular Synthons. Crystals. 2025; 15:342.

25.    Dubey RK, Dewangan HK. Rational Design and Characterization of Transdermal Patch of Irbesartan for Hypertension. Indian J Pharm Educ Res. 2020; 54(3s):s464-s472.

26.    Bala R, Pawar P, Khanna S, Arora S. Orally Dissolving Strips: A New Approach to Oral Drug Delivery System. Int J Pharm Investig. 2013; 3(2):67-76.

27.    Irfan M, Rabel S, Bukhtar Q, Qadir MI, Jabeen F, Khan A. Orally Disintegrating Films: A Modern Expansion in Drug Delivery System. Saudi Pharm J. 2015.

28.    Zhang Z, Feng S, El-Kanayati R, Karnik I, Vemula SK, Repka MA. Novel development of Poly(2-ethyl-2-oxazoline)-based mucoadhesive buccal film for poorly water-soluble drug delivery via hot-melt extrusion. Eur J Pharm Biopharm. 2025; 210.

29.    McGinnis CM, Homan K, Solomon M, et al. Dysphagia: Interprofessional Management, Impact, and Patient-Centered Care. Nutr Clin Pract. 2019; 34(1):80-95.

30.    Pawar R, Sharma R, Darwhekar G. Formulation and Evaluation of Mouth Dissolving Film of Prochlorperazine Maleate. J Drug Deliv Ther. 2019 Nov 15; 9(6):110-5.

31.    Beckett AH, Stenlake JB. Practical Pharmaceutical Chemistry. 4th ed. New Delhi: CBS Publishers & Distributors; 2023. p. 275-279.

32.    International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Harmonised Guideline: Validation of Analytical Procedures: Text and Methodology Q2(R2). Geneva: ICH; 2023.

33.    Stuart B. Infrared Spectroscopy: Fundamentals and Applications. 2nd ed. Chichester: John Wiley & Sons; 2024. p. 55-60.

34.    Waterman KC, Adami RC. Accelerated aging: prediction of chemical stability of pharmaceuticals. Int J Pharm. 2005; 293(1-2):101-125.

35.    Deshta U, Khurana B. Formulation and evaluation of mouth dissolving film of artemether. Vasc Endovascular Rev. 2025; 8(11s):99-116.

36.    Kumar GP, et al. Polyvinylpyrrolidone oral films of enrofloxacin: film characterization and drug release. Int J Pharm. 2014; 471(1-2):146-52.

37.    Nirmala D, Nandhini S, Sudhakar M. Design and evaluation of fast dissolving oral films of zolpidem by solvent casting method. Asian J Pharm Res. 2016; 6(2):67-71.

38.    ElMeshad AN, El Hagrasy AS. Characterization and optimization of orodispersible mosapride film formulations. AAPS PharmSciTech. 2011; 12(4):1384-92.

39.    Satyanarayana DA, Keshavarao KP. Fast disintegrating films containing anastrozole as a dosage form for dysphagia patients. Arch Pharm Res. 2012; 35(12):2171-82.

40.    Mashru RC, et al. Development and evaluation of fast-dissolving film of salbutamol sulphate. Drug Dev Ind Pharm. 2005; 31(1):25-34.

41.    Elshafeey AH, El-Dahmy RM. Formulation and Development of Oral Fast-Dissolving Films Loaded with Nanosuspension to Augment Paroxetine Bioavailability: In Vitro Characterization, Ex Vivo Permeation, and Pharmacokinetic Evaluation in Healthy Human Volunteers. Pharmaceutics. 2021 Nov 5; 13(11):1869.

42.    Baviskar AD, et al. FORMULATION OPTIMIZATION AND EVALUATION OF MOUTH DISSOLVING FILM OF APREPITANT. Asian J Pharm Clin Res. 2019 Sep; 12(9):154-63.

43.    Kumar GP, et al. Polyvinylpyrrolidone oral films of enrofloxacin: film characterization and drug release. Int J Pharm. 2014; 471(1-2):146-52.