Mouth dissolving films (MDFs) are a novel and patient-centric drug delivery system that has gained considerable attention in the pharmaceutical industry for its unique advantages over conventional oral dosage forms. These films are designed to disintegrate and dissolve quickly when placed on the tongue, releasing the active pharmaceutical ingredient (API) for rapid absorption. This method is particularly beneficial for populations that have difficulty swallowing pills, such as children, the elderly, and patients with dysphagia1 The composition of MDFs typically includes hydrophilic polymers like hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), or pullulan, which ensure rapid film dissolution. Plasticizers such as glycerin or polyethylene glycol are added to impart flexibility and prevent brittleness, while flavoring agents, sweeteners, and colorants enhance the sensory appeal and patient acceptability. The API is uniformly dispersed within this matrix, ensuring consistent dosing and therapeutic efficacy. One of the key advantages of MDFs is their ability to provide rapid onset of action. This is especially useful for medications requiring quick relief, such as antiemetics, analgesics, antihistamines, and drugs for acute conditions like migraines. The dissolution of the film in the oral cavity allows for buccal or sublingual absorption, bypassing the gastrointestinal tract and first-pass metabolism, which can enhance bioavailability and reduce the time to achieve therapeutic effects. The manufacturing process of MDFs involves techniques like solvent casting, hot-melt extrusion, or electrospinning, each chosen based on the properties of the drug and the desired film characteristics. Solvent casting is the most common method, where the polymer solution containing the API is cast onto a flat surface and dried to form a thin film. Quality control measures, including assessments of film thickness, tensile strength, disintegration time, and drug release profile, are critical to ensure product consistency and regulatory compliance. MDFs also offer practical advantages such as portability, convenience, and ease of administration without the need for water. These attributes enhance patient adherence to medication regimens, particularly in settings where water is not readily available or for patients who are on the go. Mouth dissolving films represent a significant advancement in drug delivery systems, combining ease of use, rapid action, and improved patient compliance. Their development continues to evolve, promising new applications and therapeutic benefits across various medical fields. This innovative technology aligns with the ongoing trend towards personalized and patient-friendly medication solutions.2,3 Telmisartan interferes with the binding of angiotensin II to the angiotensin II AT1-receptor by binding reversibly and selectively to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Telmisartan does not inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels. Absorption of Telmisartan is rapid although the amount absorbed varies. The mean absolute bioavailability for Telmisartan is about 50 %. When Telmisartan is taken with food, the reduction in the area under the plasma concentration-time curve (AUC0-?) of Telmisartan varies from approximately 6 % (40 mg dose) to approximately 19 % (160 mg dose). By 3 hours after administration, plasma concentrations are similar whether Telmisartan is taken fasting or with food. Linearity/non-linearity The small reduction in AUC is not expected to cause a reduction in the therapeutic efficacy. There is no linear relationship between doses and plasma levels. Cmax and to a lesser extent AUC increase disproportionately at doses above 40 mg.

MATERIALS AND METHODS

Materials

Telmisartan was kind sample gifted by Lupin Pharma pvt. Ltd., Mumbai. HPMC was purchased from Colorcon Asia Pvt. Ltd. Pullulan was purchased from S. D. Fine Chemicals. All other chemicals are analytical grade.

Methods

Preformulation Studies

A preformulation study is a crucial preliminary stage in the drug development process, aiming to evaluate the physicochemical properties of a drug substance before formulating it into a dosage form. This stage provides valuable insights into the drug's intrinsic characteristics, which are essential for designing an effective and stable formulation Preformulation testing's main goal is to produce data that will help the formulator create a dosage form that is safe, effective, and stable. Preformulation research was therefore done on the drug sample in order to identify it and determine compatibility. Preformulation studies are essential for establishing a solid foundation for subsequent formulation development and optimization efforts. They help in identifying potential formulation challenges and risks early in the development process, allowing for proactive problem-solving and mitigation strategies. Comprehensive preformulation data enable rational decision-making regarding formulation design, excipient selection, and process optimization to ensure the development of safe, effective, and stable drug products 5,6

Drug Excipients Compatibility Studies

Drug-excipient compatibility studies are an essential part of preformulation and formulation development processes in the pharmaceutical industry. These studies assess the compatibility of a drug substance with various excipients that are used to formulate the final dosage form. he primary purpose of drug-excipient compatibility studies is to evaluate potential interactions between the drug substance and excipients. These studies aim to identify any chemical, physical, or mechanical interactions that could affect the stability, efficacy, or safety of the final dosage form. By assessing compatibility early in the development process, formulation scientists can make informed decisions regarding excipient selection, formulation design, and process optimization. Compatibility study of drug with the excipients was determined by I.R. Spectroscopy (Shimadzu, Japan). The pellets were prepared at high compaction pressure by using KBr and the ratio of sample to KBr is 1:100. The pellets thus prepared were examined and the spectra of the drug and other ingredients in the formulations were compared with that of the pure drug.7

Formulation of Telmisartan Orodispersible Films: 

Orodispersible films of Telmisartan were prepared by solvent casting method using HPMC E5 and Pullulan as film forming materials. In this formulation, crospovidone was used as super disintegrating agent, Aspartame was used as sweetening agent, citric acid is used as saliva stimulating agent, while glycerine is used as plasticizer. The required amount of polymers where weighed and dissolved in hot water. The drug and other excipients were dissolved in ethanol and to this Plasticizer was added. Ethanolic solution was then added in to the polymeric solution and mixture was then mixed by using magnetic stirrer for 30 minutes with rotating speed 60-80rpm. The entrapped air is removed by vacuum. The resulting solution was casted slowly and with continuous flow on a glass petri plates. The plates were kept in a hot air oven at 600C for 24 Hours. The film was removed and cut into the required size of 2 x 2 (4 cm2). The formulation details of Orodispersible film were given in table 1.8-10

Weight uniformity of films

Three films of the size 2×2 cm2 were weighed individually using digital balance and the average weights were calculated.11

Thickness of Film

The thickness of the film should be measured at five locations (center and four corners), using vernier callipers and the mean thickness is calculated. Samples with air bubbles, nicks or tears and having mean thickness variation of greater than 5% are excluded from analysis.12

Folding endurance of films

Folding endurance is another procedure to estimate the mechanical properties of a film. It is measured by repeatedly folding a film at the same point until it breaks. Folding endurance value is number of times the film is folded without breaking. Higher folding endurance value depicts the more mechanical strength of a film. A direct relation exists between mechanical strength and folding endurance of films. As mechanical strength is governed by plasticizer concentration so it is clearly evident that plasticizer concentration also indirectly affects folding endurance value. The folding endurance was measured manually for the prepared films. Folding endurance of the films was determined by repeatedly folding a film at the same place till it broke. The number of times films could be folded at the same place, without breaking gives the value of folding endurance. 13,14

Surface pH of films

Surface pH was determined to reduce the irritation of oral mucosa due to alkaline or acidic pH. It was kept in the range of salivary pH.  Surface pH was determined by the films were allowed in contact with 1ml of distilled water. The surface pH was noted by bringing a combined glass electrode near the surface of films and allowing equilibrate for 1 min. Reading was recorded in pH meter.15

Drug content uniformity study

The films were tested for drug content uniformity by U.V-Spectrophotometric method. Films of 2×2 cm2 were each film was placed in 10 ml volumetric flask and diluted with phosphate buffer pH 6.8 up to 10 ml. The absorbance of the solution was measured at287nm using U.V visible spectrophotometer after suitable dilution. The percentage drug content was determined. 16,17

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. 18,19

In vitro Dissolution Study

In-vitro dissolution of Telmisartan 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 287 nm.  The volume withdrawn   at each   time   interval   was   replaced   with   fresh quantity of dissolution   medium. Cumulative percent released of Meclizine Hydrochloride was calculated and plotted against time. 20

Stability study

The accelerated stability studies were carried out according to ICH guidelines on optimized formulation. The formulation was packed in strip of aluminum foil and was stored in stability chamber maintained at 40oC and 75% RH for the period of 3 months. The Tablet were evaluated before and after 3 months for change in appearance, folding indurance, disintegration time, drug content and In vitro drug release.77.71,72

RESULTS AND DISCUSSION

Compatibility Studies (FT-IR)

Both the polymer and pure drug's infrared spectra are examined. It has been found in this investigation that there is no chemical interaction between the polymer and Telmisartan. The major peak in the drug and polymer mixture's infrared spectra was found to remain unchanged, indicating that there was no physical interaction due to bond formation between the two substances.

Physical appearance:

This parameter was checked simply with visual inspection of films and evaluation of texture by feel or touch. The observation suggests that the films were having smooth surface and Translucent.

Weight uniformity of films

Three films of the size 2×2 cm2 were weighed individually using digital balance and the average weights were calculated. Weight of the film was found in the increasing order. As the weight of polymer increases the weight of the film also increases. Weight of the films of F1- F6 was found in the range 13.61mg to 19.11 mg. Weight of film was found uniform in all batches, ensuring uniform drug distribution among the prepared films. Result was shown in table 2

Thickness of films

Thickness of the film was found in increasing order. As polymer conc. increases the thickness of the film also increases. Film thickness of formulation F1- F6 was found in the range 0.12±0.02 to 0.14±0.05 mm. The thickness of the films was measured using micro meter screw gauge. Results of thickness are shown in table 2.

Folding endurance of films:

The folding endurance of the films was determined by repeatedly folding a small strip of the films at the same place till it broke and the average folding endurance of all films was given in table 8.4 The folding endurance of the film was found between 152 to 180. Film prepared with pullulan as film forming agent (F4, F5, F6) showed higher folding endurance value than those prepared with HPMC E 5 (F1, F2, F2). From the results it was observed that pullulan produce more flexible film than HPMC. It was also observed that as the concentration of film forming agent increases, the folding endurance decreases. Among all batches, F5 batch shows higher folding endurance, while batch F3 showed lower folding endurance. Graphical representation of folding endurance was shown in figure 3.

In vitro disintegration time of films

Disintegration time for all batch of Orodispersible film formulation (F1 to F6) was found in the range of 46 seconds to 85 seconds. Formulation F5 showed lowest disintegration time of 46 seconds, while batch F3 showed higher disintegration time of 85 seconds.

The pH of the film was determined by pH paper. The pH of the film was found in the range of 6.6 to 6.8. for all formulations. All formulation was compatible saliva/buccal pH. The result was showed in table 2

Drug content uniformity study of films

Drug content uniformity for all formulation were shown in table 8.2. The prepared film formulations were analyzed for drug content and  it  was  observed  that  all  the formulation   found   to   contain   almost   uniform quantity of drug as per content uniformity studies indicating reproducible technique. Drug content for all formulation was found to be in the range of 96.13 % to 99.82% which shows uniformity of drug content in all formulation. Batch F5 formulation showed highest 99.82 percent of drug content.

In Vitro Dissolution Studies

In-vitro dissolution of Telmisartan orodispersible films was studied in USP Type 2 dissolution test apparatus, 900 ml phosphate buffer pH 6.8 solution was used as dissolution medium. Formulations F1, F2 and F3 prepared with HPMC E5 as film forming materials showed drug release of 98.05%, 95.42% and 92.04 % respectively in 15 min time duration. Formulation F4, F5, and F6 prepared with pullulan as film forming agent showed 99.63%, 102.30% and 98.24% drug release respectively in 15 min time. All the formulation showed rapid drug release because of presence of super disintegrating agent crospovidone . All batch formulation showed more than 65% drug release in first 5 min time interval. Among the formulation batch F5 prepared with pullulan (200mg) as film forming agent showed fastest drug release ie almost 102.30% in just 15 min time, which was highest among the other batch formulation. Film prepared with pullulan showed higher and faster drug release than film prepared with HPMC E5. Data for in vitro drug release of orodispersible film was shown in figure 5.

Orodispersible film of Telmisartan formulation showing promising results in term of lowest disintegration time and higher drug release, was selected for stability studies. According to ICH guidelines, optimized formulations F5 were stored at 400C temperature and 75% relative humidity (RH) for a period of 3 months. Formulation was evaluated for appearance, folding endurance, drug content, disintegration time and In vitro drug release. At the end of 3 months, no significant difference was observed in folding endurance, drug content, disintegration time and in vitro drug release. From the stability study it was concluded that telmisartan orodispersible film formulation F5 was found to be stable. The results of stability data were shown in table 3