The first prescription OFDF, which uses API as an ondansetron (Zuplenz), was approved by the Food and Drug Administration in 2010. Suboxone was the second OFDF to receive approval from the FDA. Listerine OFDFs have now gained popularity all over the world and are now sold as breath fresheners. There are a number of OFDFs on the market right now, and physicians recommend them. Table 1 contains a list of some of the OFDFs that are marketed as over-the-counter and prescription medications. OFDFs are produced as big sheets that be trimmed to the appropriate size and dosage¹³. OFDFs for a variety of medications with either systemic or local activity have been developed. OFDFs are utilized for oral ulcers, cold sores, toothaches, and local anesthesia ¹⁴. They are used to treat pain, nausea, vomiting, gastrointestinal problems, sore throats, coughs, and central nervous system illnesses.

Figure 1. Diagram showing the administration and release of oral fast dissolving film (OFDF) (A) Opening the sealed ODF container, applying it to the upper side of tongue without any fluids, and telling the user to avoid mastication (B) Salivation aquation, breaking down, and ODF dissolution (C): Due to the pH variation of the gastro-intestinal tract, Saliva naturally ingests dissolved ODF, which then makes its way to the stomach for systemic absorption¹²⁶.

Oral Fast Dissolving Films (ofdf):

A dosage form can instantly hydrate, adhere, and dissolve to deliver the medication when it is placed on the surface of the tongue or in the oral cavity. This kind of dosage form is called as a strip or film and is typically made of a hydrocolloid, though it can also be a bioadhesive polymer^21,22. They are also known as oral-dissolving, fast-melting, quick-dispersing, and fast-dissolving films²³. OFDF can offer a practical and efficient way to get active substances, like medicinal compounds and breath fresheners, into the mucosa of both people and animals²⁴. It makes it possible to administer the medication sublingually, buccally, or intragastrically to the bloodstream²⁵. Rapid medication absorption through the sublingual route is possible as soon as OFDF are taken, which ultimately results in a speedy beginning of pharmacological action. When creating OFDF, it is essential to select the right one integrated excipient and or ingredients because OFDF must dissolve and/or disintegrate rapidly in the buccal cavity. Based on its intended purpose, the formulation may contain additional ingredients in addition to the water-dissolving polymer²⁶, namely.

Figure 2. OFDF¹²⁷.

Special Features of OFDF^27,28

1. An elegantly thin narrow or film.

2. Comes in a variety of shapes and sizes.

3. Unobtrusive.

4. Enhanced adherence of mucosa.

5. Quick breakdown and disintegration.

6. Fast drug release.

7. Avoid first pass effect.

Merits and Demerits:

Merits^{29,30,31,32,33}

1. The medication directly reaches the systemic circulation, avoiding the first-pass impact. Many medications, including peptides steroids and other proteins, and insulin may not stable when they come into contact with the gastrointestinal tract's digestive secretions. Moreover, Neither the speed at which food is consumed nor the timing of stomach emptying influences the rate of drug absorption.

2. A greater surface area in the mouth cavity promotes quick dissolution and disintegration.

3. Oral films are less fragile than OFDTs because they are more flexible. Transportation, as well as the processing and storage of consumers, are thereby made simpler.

4. The bitter flavor is concealed by using the flavor-masking technique of medications and achieve a pleasant taste instead. Therefore, these are used in pediatrics.

5. Because there is less discomfort, there is greater patient compliance associated with injections, the ability to provide drugs to unconscious or the patients under coma, and the convenience of intake of medicine in comparison to an injection and medicine.

6. The low water demand and ease of swallowing have led to higher levels of acceptability among dysphagic patients.

7. Beneficial for situations where a quick response is necessary, such motion sickness, sudden allergic reactions, coughing, bronchitis, or asthma.

8. Increase buccal bioavailability of substances which are affected by first-pass metabolism.

9. Reducing the dosage by avoiding the first-pass metabolism may lessen the adverse effects of the compounds.

10. OFDFs are easier for geriatric, paediatric, and paralyzed patients to ingest without water and without choking hazards, which increases patient compliance.

11. Remain stable for a longer period of duration or time because the medication is consumed in a solid dosage form. till it is finished.

12. Lowering the dosage improves the medication's safety and efficacy while minimizing negative effects.

Demerits^29,30,31,34

1. There is no way to incorporate high doses.

2. Rapid drug clearance for local action is brought on by continual salivation (0.5-2L/day), which subsequently dilutes the medication and requires frequent administration.

3. Because OFDFs are water-soluble and prone to degradation, they are difficult to protect.

4. They require particular packing and storage equipment.

5. OFDFs are unable to contain medications that are absorbed through active diffusion.

6. Consumption of food and drinks could be restricted.

7. Drugs that irritate the mucosa, this route cannot be used to deliver anything bitter, disagreeable, or odorous.

Classification of OFDF³⁵

Flash release wafer.

Mucoadhesive melt-away wafer.

Mucoadhesive sustained release wafer.

Mechanism of buccal absorption:

The process of buccal medication absorption is primarily driven by concentration gradients and involves nonionized molecules passively diffusing across the intercellular pores in the epithelium. Passive transfer of not-ionic molecules is the primary pathway of transport through the lipid membrane of the buccal cavity. The mucosa of the mouth has been described as a lipoidal barrier to drug transit, similar to many other mucosal membranes; the more quickly a drug molecule is absorbed, the more lipophilic it is. A first order rate method could appropriately characterize the kinetics of medication absorption via the mucosa of the buccal cavity. Medication absorption via the buccal mucosa could be inhibited by a number of possible factors. Salivary secretion alters, according to Dearden and Tomlison (1971) the concentration of medication in the mouth, which subsequently impacts the buccal absorption kinetics of drug solution. Linear relationship between salivary secretion and time represents the following equation.³⁶

-dm Kc

---------- = -----------

dt ViVt

Where,

M - At time t, Drug mass in the oral cavity.

K - Constant proportionality.

Vi - quantity of the solution administered orally.

Vt - The rate of salivary secretion.

C - concentration of medicine in the oral cavity over time.

Methodology for Preparation of Oral Fast Dissolving Film:

Numerous methods, including solvent casting, rolling, hot-melt extrusion, semi-solid casting, and solid dispersion extrusion, have been developed to make OFDFs because it is a challenging process. Researchers and industry most commonly employ two processes for making films: hot-melt extrusion and solvent casting^68-70.

Solvent Casting Method:

This is one of the older techniques for creating OFDFs is solvent casting. This process is hydrous, and it is used to create medicines that are available in dose forms that are both thermostable and thermolabile⁷¹. In order to prepare plant extracts or active pharmaceutical ingredients, active ingredients must first be soluble in purified water or another evaporative solvent that the pharmaceuticals drugs may readily dissolve in. The mixture is then thoroughly mixed with a magnetic stirrer to ensure consistency. The qualities of the active substances are taken into consideration when choosing solvents. These characteristics include temperature sensitivity, solvent–drug compatibility, polymorphism, and interaction of the active ingredient with excipients, particularly polymeric materials that form films. Each of the necessary excipients, plasticizer, coloring agent, and film-forming polymer is produced separately in purified water. The necessary liquid solution is prepared, then to guarantee homogeneity it is stirred once more. This substance is referred to as the "film dope." After applying the film dope on laboratory-scale Petri plates, the dishes are heated to between 40 and 50 °C for a full day. The films are taken out, cut off to the appropriate sizes, and kept in aluminum foil for characterisation once they have completely dried. On an impregnated paper roll, on an industrial scale, solvent cast film deposition procedures are used to apply the film dope. To remove the solvents, the spread medium is put through a convection chamber. The films are split into tiny pieces when they have dried, and they are either individually wrapped in aluminum foil or sealed in airtight containers. To prevent the impacts of moisture, certain precautions are taken when packing films. One of the things that affects a film's mechanical qualities and stability is moisture. Moreover, solutions' viscosity can only be maintained by managing the temperature ^72-78. As volatile ingredients require lower temperatures to be removed from the films, the solvent casting approach works best to prepare active molecules that are responsive to light and heat. However, there are certain drawbacks to this approach. While preparation, small quantities of solvents may remain, which impairs compendial acceptance. Furthermore, extra precautions must be taken while handling volatile or flammable solvents, such as ethanol and methanol, to prevent fire⁷⁹.

Figure 3. description of solvent casting method ¹²⁸

Hot-Melt Extrusion Method:

Solvent casting was the procedure formerly used to make oral thin films. While this particular method of film preparation allows for flexibility, consistency, clarity, and the appropriate thicknesses to help in drug loading, it is restricted by increased tensile strength and lower elasticity⁸⁰. Another limitation of films made by solvent casting techniques is the usage of solvents that are organic for some polymer compounds that have a low liquid solubility. solvents that are organic are dangerous, and their traces make it difficult to dispose of garbage, which leads to a number of environmental problems^81,82. The pharmaceutical industry needed a different approach to address these problems, and it was discovered that the hot-melt extrusion technology offered a number of benefits. First off, no solvents are needed for the processing of oral films. Additionally, this procedure is cost-effective since it produces extrudates in a single step, eliminating the need to compress medications and excipients throughout processing. Drug bioavailability is enhanced by the uniform distribution of particles made possible by the liquid condition of active ingredients and polymers after mixing⁸³. In the past, sustained drug releasing tablets and granules were made using the hot-melt extrusion method for transmucosal as well as transdermal delivery systems for drugs, such as skin patches⁸⁴.

Several researchers have reported using this method to produce OFDFs. But in the past few decades, this technique of producing OFDFs has become more and more widespread. Using this method, it is simple to extrude one or more medications to create the appropriate dose forms for drug delivery. Rather than employing the solvent casting procedure, excipients inside a film for medicinal delivery⁸⁵. The hot-melt extruded process produces strip by mixing the medication, hydrophilic polymers which form film, plasticizing agent, surface active agents, and further necessary ingredients in the proper quantities to achieve equal blending. After blending, the extruded material is sent to a heated barrel via a hopper to create consistent films that are thinner than one millimeter. In order to guarantee that films adhere to the mucosal surface, ingredients are occasionally additionally added during the first processing⁸⁶. Future potential to develop films for gastroretentive delivery of drugs as well as multiple-layered films for transdermal medicine release applications will result from the hot-melt extrusion method of film manufacturing. Hot-melt extrusion techniques can be used in medical devices to include medications into biodegradable stents and catheters. These viewpoints could boost commercialization, innovation, and research in academic institutions, research centers, and the biotechnology and pharmaceutical businesses.

Figure 4 Description of Hot melt extrusion method ¹²⁹.

Semi-solid Casting Method:

The development of OFDFs also employs the semi-solid casting technique. This approach involves first preparing film-forming and water-soluble solutions, which are then mixed into a polymer slurry that is insoluble in acid. To get the desired gel mass, plasticizers are proportionately incorporated to the previously generated solution. The resulting gelatinous mass is carefully controlled and cast into films between 0.015 and 0.05 inches thick⁸⁷.

Rolling Method:

Another method for preparing OFDFs is rolling, which involves rolling drug solutions on a drum. Either distilled water or an alcohol and water mixture is used to dissolve the drugs. On the rolling device, the already mixed solutions are rolled, and then After drying, the thin film is sliced into the required sizes. The already mixed solution is made up of the film-forming polymer, polar solvent, active agent, and required excipients, which is then added to the tank. To achieve the required thickness, a controlled valve pump feeds the fluid with the intended dose ⁸⁸.

Figure 5 Description of rolling method¹³⁰.

3-D Printing Method

In recent years, scientists have also attempted to create OFDFs through the use of a novel method called 3D printing. This method, which is additive in nature, depends on the deposition of several ingredient layers⁸⁹. Researchers have manufactured OFDFs through the use of 3D printing techniques; in the last stage of production, liquid or semi-solid components solidify to form the final product. The most popular way to create medication delivery systems using 3D printing is by extrusion technologies with fused deposition⁹⁰. The creation of aripiprazole OFDFs is one instance of this process. The first step in the preparation of aripiprazole filaments is hot-melt extrusion, followed by PVA mixing and ethanol moistening before drying. An extruder is used in the preparation of the film filaments. A steady pace is used to feed and extrude the mixed powder through the die. After that, the film filament is gathered and utilized once more to create 3D-modeled OFDFs. The lengths, widths, and depths of the manufactured OFDFs are specified⁹¹.

Solid Dispersion Extrusion:

When amorphous hydrophilic polymers are available, the process of dispersing one or more APIs in an inert carrier using methods like hot melt extrusion is known as "solid dispersion extrusion". This procedure involves the extrusion of the medication along with soluble ingredients, resulting in the solid dispersions. Die-cutting machines are then employed to form the film from the solid dispersions⁹².

Evaluation and Characterization:

It is important to characterize and evaluate prepared OFDFs. A variety of techniques, including mechanical properties, transparency, contact angle, to assess prepared OFDFs in line with planned goals and objectives, tests for DT (disintegration time), moisture content, visual surface pH assessment, swelling index, dissolution, and content homogeneity have been established^93-100.

Organoleptic Evaluation:

One method of assessing taste that can be done in vitro or in vivo is organoleptic evaluation. Specialized, regulated Human tasting panels are employed in its execution. While regarding the taste examination approach, in vivo evaluation uses human subjects, electronic taste sensors are used to evaluate the taste of films in vitro⁴⁰. Commercially available taste sensing devices like α sstree (Alphamos) and TS-5000Z (Insent) are used for OFDF evaluation. Seven lipid membrane sensors, one for each of the following taste attributes: salty, sour, umami, astringent, and bitter, are installed in the TS-5000Z system. The alternative system, α astree, has seven ChemFET-sensors intended for use in pharmaceutical applications^101,102. Due to the fact that bad taste lower elderly patient and therapy compliance, pediatric, and bedridden patients, taste-sensing devices have drawn attention in the pharmaceutical industry. These artificial tongues offer a novel way to screen drug-filled films for unpleasant or poor tastes. The taste of dose forms can be evaluated using in vitro taste sensing techniques. Tastes of formulations and the amount of sweetener in taste masking formulations are evaluated using both in vitro and in vivo techniques¹⁰³.

The Morphology of Surfaces:

OFDFs' surface morphology or visual examination can provide information on their transparency, uniformity, and color⁹⁶. SEM (scanning electron microscopy) and LM (light microscopy) have been employed for this. Because of its development and uniform surfaces absent of pores, SEM performance can be utilized to evaluate the superior quality of OFDFs. Films of one centimeter square were positioned over a glass slide on a microscope stage, allowing for the micro-level observation of the film's structure; a deeper look at the structure of the film was obtained using SEM¹⁰⁴.

Disintegration Time:

Many disintegration instruments are mentioned in pharmacopoeias for use in calculating film disintegration times (DTs). Since DT varies with formulations, DT depends on the film's composition. OFDFs often break down after 5–30 seconds. There are currently no clear pharmacopeial guidelines available for figuring out what the DTs of OFDFs are⁹⁴. The Petri dish method is the approach most investigators use to determine the DTs of OFDF formulations, however there are two ways available: slide frame methods and Petri dish method¹⁰⁵.

Slide Frame Technique:

Films are put on a Petri dish or a glass slide frame when using the slide frame method. After being applied to the film, the duration of time it takes for pure distilled water droplets to disintegrate is noted¹⁰⁰.

Petri Dish Method:

Using this procedure, First, add 10 milliliters of warm distilled water to the Petri plate, then add 2 cm2 films to it. After that, given the Petri dish a little shake to determine how long the film will take to dissolve. The total duration of time the strip takes to breakdown is known as the disintegration time. The identical procedure should be carried out three times for optimal results, and the averages and standard deviations of the outcomes should be noted¹⁰⁶.

In Vitro Dissolution Test:

In vitro film dissolving times have been measured using two authorized paddles as well as basket apparatus. Sink conditions have to be kept consistent during the dissolving experiment. Testing became challenging when the film occasionally floats above the medium during disintegration. Since paddle apparatuses are the main source of this issue, the basket apparatus approach is recommended. The study used pure water, 0.1 Normal HCL, phosphate-buffered solutions having pH of 6.8, stomach and intestinal fluids, and purified water in both apparatuses. Five milliliter aliquots were taken six times a minute, at 8, 10, 12, 16, 20, and 30 minutes. A UV- spectrophotometer was used to evaluate the extracted samples¹⁰⁷.

Swelling Properties:

Polymers are employed to create films that are hydrophilic in nature, which determines the swelling properties of OFDFs¹⁰⁸. For the release of medications, the rate and degree of film swelling are important. However, these characteristics are typically taken into consideration to examine drug release patterns and film mucoadhesion¹⁰⁹. Films' swelling profile has been enhanced by the application of simulated saliva solution. The percentage of hydration was used to evaluate the swelling of the films. In order to do this, films were first weighed (W1) and immersed for a specific period of time in simulated saliva. Following that, the samples were removed, the surfaces were cleared of any extra water, and they were weighed once more (W2). The following formula was used to determine the % hydration^110,111:

W₂ -W₁

Hydration (%) = -------------------- x 100

W₁

To measure the amount of swelling is present, Wi (the film was first weighed) and after that it was placed on a wire mesh and dipped in medium. The weight of the film was recorded until regular periods of time passed and no further W_f weight growth was noticed. The amount of swelling was measured with the use of the equation described below⁴³:

Wf -Wi

Degree of swelling = -----------

Surface Ph:

The surface of the oral cavity has a pH range of 5.5 to 7.4. Given that OFDF formulations with very acidic or alkaline pHs irritate mucosal tissues, OFDF pH values must fall between the range of the mouth cavity pH. This is because OFDFs are meant to dissolve rapidly inside the mouth cavity after being positioned on the tip of the tongue. Films were chosen at random to measure the pH of their surfaces. Since it is impossible to estimate the pH of a dry film, first, the films were dissolved in two milliliters of purified water in order to measure the pH and alter the film state. After allowing the pH value to stabilize for ten minutes, The electrode that is part of the pH meter was positioned on the surface of the fluid, and the reading was noted¹¹².

Moisture Loss and Moisture Uptake:

The film is weighed and then dried within a desiccator with for three days, the calcium carbonate was used to determine the percentage of moisture loss. Following a three-day period, after removing the films and weighing them again, the moisture loss is calculated using the following formula:

Initial weight –final weight

% Moisture loss = --------------------------------------- x100

Initial weight

The percentage moisture uptake of a film can be measured using the method described below, when it has been exposed for a period of seven days to a room temperature environment having a humidity level of 75% ¹¹³:

Final weight -Initial weight

% Moisture uptake = ----------------------------------- x100

Initial weight

Mechanical Properties:

The mechanical parameters of OFDFs have been determined using the results for tensile strength, Young's modulus, folding endurance, percent elongation, and tear resistance¹¹⁴. Studies has shown that fragile and softer polymers have lower values of Young's modulus, tensile strength and elongation than do their strong and hard counterparts¹¹⁵. Moreover, the mechanical characteristics of films are changed by production processes.

Thickness:

To ensure that the medication contents are consistent, the film thickness is measured using a micrometer, also known as a screw gauge. The precision of the drug dosage is dependent on the consistency of the film thickness. Film thicknesses were measured from the center of each film as well as from its four corners, and average values were recorded¹¹⁶.

Dryness:

To determine whether films adhere to a piece of paper, tests called tack or dryness tests are conducted. Tack is the term used to describe the persistence of films as seen when there's a piece of paper placed in between them. A few beneficial phases of film drying are Set-to-touch, dry-to-recoat, dry-through, tack-free, dry-print, and dry-to-touch and dry-hard. Film dryness has been evaluated using this test^93,94.

Tensile strength:

One of the most important mechanical tests for determining the strength and flexibility of films is the tensile strength (TS) test. Strength of tensile in the OFDFs refers to the maximum force and pressure that a film can bear before breaking. The force that breaks a film is divided by the film's original size to determine the total stress (TS)¹¹⁷.

Percentage Elongation:

Any object that is under stress will change in size and shape a process known as elongation ¹⁸. It can be as determined through a texture analyzer which helps in the prediction of the flexibility of polymers utilized in formulations. The percentage of elongation indicates a film's capacity to stretch before breaking down; yet, simply matching the film's length at breakage to its initial length will yield the percentage of elongation ^118,119. It can be computed by using the formula in mathematics¹²⁰.

Change in length at break

% Elongation = --------------------------------------- x 100

Initial length

Young’s Modulus:

The degree of stiffness or flexibility in the film is reflected in Young's modulus. It can be found by graphing the relationship and connection between the slopes representing Young's moduli and the stress-strain curves. It describes resistance to deformation films. The tensile modulus increases with increasing slope and vice versa¹²¹. In other words, films that are hard and brittle have greater Young's modulus values. the applied stress to strain ratio, which may be calculated using the formula²², can be used to display the results.

Slope

Young’s modulus = ------------------------------- x 100

Film thickness x speed

Folding Endurance:

An evaluation test called to assess the mechanical properties; FE (folding endurance) is employed of OFDFs. When it comes to delivering the patient the dosage form precisely and without breaking, this is an important parameter. With FE, measuring a film's elasticity is simple. The method of calculation involves repeatedly folding a sheet at 180° angles until cracks show up. There is a clear correlation between FE and film mechanical power. The mechanical strength will increase with a higher FE value and vice versa. However, because the quantity of plasticizer is used in the film's composition influences mechanical strength, the FE value is indirectly impacted by plasticizer concentration. Tests should be conducted three times for improved outcomes^122,123.

Content Uniformity:

Pharmacopoeias provide a standard assay method that can be used to calculate the content uniformity of formulations. It is estimated that drug content in films is examined 94. First, dissolve the 1 cm2 OFDF in buffer solution of quantity 100ml for this test. Make 2mL aliquots out of that mixture and dilute them up to 10mL with buffer solution. The diluted sample should next be measured with an ultraviolet-visible spectrophotometer, and the absorbance adjusted in accordance with the active component that was utilized. In order to verify drug content homogeneity, The amount of drug present in the film can be estimated with the aid of the absorbance value¹²⁴.

Packaging of Films:

Appropriate film packaging is necessary to preserve the mechanical properties of OFDF formulations and ensure their stability during storage. The packing material acts as a barrier to keep moisture out, light, heat, and oxygen. Film storage can be achieved with commercially available packaging materials such as foil sheets, plastic pouches, blister packs, and aluminum pouches. But none of them are good at keeping film products stable while they are being stored¹⁰⁰. The most popular and effective packaging for films is aluminum foil packaging, which protects the OFDFs from deterioration, light, heat, and moisture. In order to establish airtight conditions, films require not only primary packing but also secondary packaging containers for storage¹⁸. Commercially, OFDFs and basic films in sizes 1 × 2cm2, 2 × 2 cm2, and 3 × 2 cm2 are offered on the market¹²⁴. OFDFs may be packaged in pouches to hold films of any size and shape, and the process is inexpensive, safe, and simple while taking some time to complete¹²⁵. There are many films on the market that come in single or multiple unit dose packs. Pfizer Consumer Healthcare sells a single-dose film for breath freshening under the brand name PocketpaksTM. In a similar vein, APR-Labtec introduced a packaging method for Rapid® films it has 6 films and is available in multiple dosages¹²⁴. The different film packing approach uses an automated process that is computer-driven designed to boost patient compliance and simplicity of usage¹⁸.

Conclusions and Future Perspective:

Over the past ten years, OFDFs have gained popularity as a medication delivery mechanism. Patients' adherence to conventional dosage forms is reduced by a number of issues related to administration, bioavailability, solubility, and taste. However, to improve adherence, a unique drug delivery method employing oral thin films composed of synthetic, natural, and semi-synthetic polymers has been developed. Films for the oral route can be created utilizing a variety of procedures, and we can also use these techniques to create films for the rectal, vaginal, ophthalmic, and transdermal routes of drug delivery. As a result, innovative films can be utilized as substitutes for traditional dosage forms and can readily address the issues related to traditional dosage forms. There are several difficulties in the formulation and manufacturing of the unique dosage film formulation, but these have all been resolved by formulation optimization. Film technology appears to have a bright future in delivery of drugs, providing a means of overcoming the limitations correlated with traditional technologies.

REFERENCES:

1. Siddiqui MN, Garg G, Sharma PK. A short review on “A novel approach in oral fast dissolving drug delivery system and their patents”. Adv Biol Res. 2011 Nov;5(6):291-303.

2. Chan R. Oral thin films: Realms of Possibility. ONdrugDelivery Mag. 2016 Jul; 69:12-7.

3. Patel AR, Prajapati DS, Raval JA. Fast dissolving films (FDFs) as a newer venture in fast dissolving dosage forms. Int. J. Drug Dev. Res. 2010 Apr;2(2):232-4.

4. Zaman M, Hassan R, Amjad MW, Khan SM, Raja MA, Shah SS, Siddique W, Aman W, Abid Z, Butt MH. Formulation of instant disintegrating buccal films without using disintegrant: An in-vitro study. Pakistan Journal of Pharmaceutical Sciences. 2021 Nov 2;34.

5. Wright D, Tomlin S. CPD-How to help if a patient can't swallow. Pharmaceutical Journal. 2011; 286(7643): 271.

6. Bandari S, Mittapalli RK, Gannu R. Orodispersible tablets: An overview. Asian Journal of Pharmaceutics (AJP). 2008;2(1).

7. Mahboob MB, Riaz T, Jamshaid M, Bashir I, Zulfiqar S. Oral films: A comprehensive review. International Current Pharmaceutical Journal. 2016 Nov 18;5(12):111-7.

8. Salawi A. An insight into preparatory methods and characterization of orodispersible film—A review. Pharmaceuticals. 2022 Jul 9;15(7):844.

9. Hussain MW, Kushwaha P, Rahman MA, Akhtar J. Development and evaluation of fast dissolving film for oro-buccal drug delivery of chlorpromazine. Indian Journal of Pharmaceutical Education and Research. 2017 Oct 1;51(4):S539-47.

10. Karki S, Kim H, Na SJ, Shin D, Jo K, Lee J. Thin films as an emerging platform for drug delivery. asian journal of pharmaceutical sciences. 2016 Oct 1;11(5):559-74.

11. Özakar RS, Özakar E. Current overview of oral thin films. Turkish journal of pharmaceutical sciences. 2021 Feb;18(1):111.

12. Gupta MS, Kumar TP, Gowda DV. Orodispersible Thin Film: A new patient-centered innovation. Journal of Drug Delivery Science and Technology. 2020 Oct 1;59:101843.

13. Desai PP, Date AA, Patravale VB. Overcoming poor oral bioavailability using nanoparticle formulations–opportunities and limitations. Drug Discovery Today: Technologies. 2012 Jun 1;9(2):e87-95.

14. Sharma I, Sharma V. A comprehensive review on fast dissolving tablet technology. Journal of applied pharmaceutical science. 2011 Jul 30(Issue):50-8.

15. Mishra R, Amin A. Formulation and characterization of rapidly dissolving films of cetirizine hydrochloride using pullulan as a film forming agent. Indian journal of pharmaceutical education and research. 2011 Jan 1;45(1):71-7.

16. Hoffmann EM, Breitenbach A, Breitkreutz J. Advances in orodispersible films for drug delivery. Expert opinion on drug delivery. 2011 Mar 1; 8(3): 299-316.

17. Krause J, Breitkreutz J. Improving drug delivery in paediatric medicine. Pharmaceutical Medicine. 2008 Jan;22:41-50.

18. Dixit RP, Puthli SP. Oral strip technology: Overview and future potential. Journal of controlled release. 2009 Oct 15;139(2):94-107.

19. Preis MK. Oromucosal film preparations for pharmaceutical use-formulation development and analytical characterization (Doctoral dissertation, Universitäts-und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf).

20. Wasilewska K, Winnicka K. How to assess orodispersible film quality? A review of applied methods and their modifications. Acta Pharmaceutica. 2019 Jun 30;69(2):155-76.

21. Ghosh TK, Pfister WR. Drug delivery to the oral cavity: molecules to market. CRC Press; 2005 Feb 28.

22. Dinge A, Nagarsenker M. Formulation and evaluation of fast dissolving films for delivery of triclosan to the oral cavity. Aaps Pharmscitech. 2008 Jun; 9: 349-56.

23. Saigal N, Baboota S, Ahuja A, Ali J. Fast-dissolving intra-oral drug delivery systems. Expert Opinion on Therapeutic Patents. 2008 Jul 1;18(7):769-81.

24. Barnhart, S.D.; Full, A.P.; Moritz, C. Rapidly dissolving films for delivery of pharmaceutical or cosmetic agents. U.S. Patent 60/513,547, December 03, 2004.

25. Thin film drug delivery, http://en.wikipedia.org/wiki/Thin_film_ drug_delivery.

26. Hang, J. Dissolving films. U.S. Patent 20070184093, August 09, 2007.

27. Bhyan B, Jangra S, Kaur M, Singh H. Orally fast dissolving films: innovations in formulation and technology. Int J Pharm Sci Rev Res. 2011 Jul;9(2):9-15.

28. Bala R, Pawar P, Khanna S, Arora S. Orally dissolving strips: A new approach to oral drug delivery system. International journal of pharmaceutical investigation. 2013 Apr;3(2):67.

29. Karki S, Kim H, Na SJ, Shin D, Jo K, Lee J. Thin films as an emerging platform for drug delivery. asian journal of pharmaceutical sciences. 2016 Oct 1;11(5):559-74.

30. Kathpalia H, Gupte A. An introduction to fast dissolving oral thin film drug delivery systems: a review. Current drug delivery. 2013 Dec 1;10(6):667-84.

31. Saini P, Kumar A, Sharma P, Visht S. Fast disintegrating oral films: A recent trend of drug delivery. Int J Drug Dev Res. 2012 Oct;4(4):80-94.

32. Jain A, Ahirwar HC, Tayal S, Mohanty PK. Fast dissolving oral films: a tabular update. Journal of Drug Delivery and Therapeutics. 2018 Jul 14;8(4):10-9.

33. Khatoon N, Raghavendra Rao NG, Reddy BM, Overview on Fast Dissolving Oral Films, International Journal of Pharmaceutical Sciences and Drug Research, 2013; 1(1):63-75.

34. Patil BS, Tate SS, Kulkarni U, Hariprasanna RC, Wadageri GV. Development and in-vitro evaluation of mucoadhesive buccal tablets of Tizanidine hydrochloride using natural polymer xanthan gum. Int J Pharm Sci. 2011;8(2):140-6.

35. Perioli L, Ambrogi V, Angelici F, Ricci M, Giovagnoli S, Capuccella M, Rossi C. Development of mucoadhesive patches for buccal administration of ibuprofen. Journal of controlled release. 2004 Sep 14;99(1):73-82.

36. Patel KV, Patel ND, Dodiya HD, Shelat PK. Buccal bioadhesive drug delivery system: an overview. Int J Pharm Bio Arch. 2011;2(2):600-9.

37. Gupta SK, Singhvi IJ, Shirsat M, Karwani G, Agarwal A. Buccal adhesive drug delivery system: a review. Asian J. Biochemical and pharmaceutical research2011. 2011 Apr;2(1):105-14.

38. Siddique W, Sarfraz RM, Zaman M, Butt MH, Hayat Z, Gul M, Gul M, Asghar F. Impact of polymer and plasticizer on mechanical properties of film: A quality by design approach. Latin American Journal of Pharmacy. 2021 Jan 1;40(12):3002-8.

39. Allen E, Davidson R, LaRosa T, Reid D, inventors; Concept Matrix Solutions, assignee. Oral dissolvable film that includes plant extract. United States patent US 10,307,397. 2019 Jun 4.

40. Preis M, Pein M, Breitkreutz J. Development of a taste-masked orodispersible film containing dimenhydrinate. Pharmaceutics. 2012 Oct 26;4(4):551-62.

41. Horstmann M, Laux W, Hungerbach S, inventors; LTS Lohmann Therapie Systeme GmbH and Co KG, assignee. Rapidly disintegrating sheet-like presentations of multiple dosage units. United States patent US 5,629,003. 1997 May 13.

42. Garsuch V, Breitkreutz J. Comparative investigations on different polymers for the preparation of fast-dissolving oral films. Journal of Pharmacy and Pharmacology. 2010 Apr;62(4):539-45.

43. Irfan M, Rabel S, Bukhtar Q, Qadir MI, Jabeen F, Khan A. Orally disintegrating films: A modern expansion in drug delivery system. Saudi pharmaceutical journal. 2016 Sep 1;24(5):537-46.

44. Boateng JS, Matthews KH, Auffret AD, Humphrey MJ, Stevens HN, Eccleston GM. In vitro drug release studies of polymeric freeze-dried wafers and solvent-cast films using paracetamol as a model soluble drug. International Journal of Pharmaceutics. 2009 Aug 13;378(1-2):66-72.

45. Boateng JS, Stevens HN, Eccleston GM, Auffret AD, Humphrey MJ, Matthews KH. Development and mechanical characterization of solvent-cast polymeric films as potential drug delivery systems to mucosal surfaces. Drug development and industrial pharmacy. 2009 Aug 1;35(8):986-96.

46. Pathare YS, Hastak VS, Bajaj AN. Polymers used for fast disintegrating oral films: a review. Int. J. Pharm. Sci. Rev. Res. 2013 Jul;21(1):169-78.

47. Sharma R, Parikh RK, Gohel MC, Soniwala MM. Development of taste masked film of valdecoxib for oral use. Indian Journal of Pharmaceutical Sciences. 2007 Mar 1;69(2).

48. Kulkarni AS, Deokule HA, Mane MS, Ghadge DM. Exploration of different polymers for use in the formulation of oral fast dissolving strips. J Curr Pharm Res. 2010;2(1):33-5.

49. Ali S, Quadir A. High molecular weight povidone polymer-based films for fast dissolving drug delivery applications. Drug Delivery Technology. 2007;7(6):36-43.

50. Cao N, Yang X, Fu Y. Effects of various plasticizers on mechanical and water vapor barrier properties of gelatin films. Food hydrocolloids. 2009 May 1;23(3):729-35.

51. Hanif M, Zaman M, Chaurasiya V. Polymers used in buccal film: a review. Designed Monomers and Polymers. 2015 Feb 17;18(2):105-11.

52. Pawar R, Sharma R, Sharma P, Darwhekar GN. A review on mouth dissolving film. Journal of Drug delivery and Therapeutics. 2019 Nov 15;9(6):206-10.

53. Sau-hung S, Robert S. Lori. Fast dissolving orally consumable films, US Patent.;6(596):298.

54. Prakash I, DuBois GE, Clos JF, Wilkens KL, Fosdick LE. Development of rebiana, a natural, non-caloric sweetener. Food and Chemical Toxicology. 2008 Jul 1;46(7): S75-82.

55. Israel K, Leo M, Salivary stimulant, U.S Patent, 1989; 4820506.

56. http://www. Patent storm.us /patents/ 6740332/claims. Html.

57. Zyck DJ, Dzija MR, Chapdelaine AH, inventors; Wm Wrigley Jr Co, assignee. Edible film formulations containing maltodextrin. United States patent US 6,740,332. 2004 May 25.

58. Technical Brief: Particle Sciences Drug Development Services, Vol 3 2010.

59. Coppens KA, Hall MJ, Mitchell SA, Read MD. Hypronlellose, ethylcellulose, and polyethylene oxide use in hot melt extrusion. Pharmaceutical technology (2003). 2006;30(1):62-70.

60. Giovino C, Ayensu I, Tetteh J, Boateng JS. An integrated buccal delivery system combining chitosan films impregnated with peptide loaded PEG-b-PLA nanoparticles. Colloids and Surfaces B: Biointerfaces. 2013 Dec 1; 112:9-15.

61. Murata Y, Isobe T, Kofuji K, Nishida N, Kamaguchi R. Preparation of fast dissolving films for oral dosage from natural polysaccharides. Materials. 2010 Aug 9;3(8):4291-9.

62. Nagar P, Chauhan I, Yasir M. Insights into Polymers: Film Formers in Mouth Dissolving Films. Drug invention today. 2011 Dec 1;3(12).

63. Arora L, Chakraborty T. A review on new generation orodispersible films and its novel approaches. Indo Am. J. Pharm. Res. 2017 Jan; 7:7451-70.

64. Shinkar DM, Dhake AS, Setty CM. Drug delivery from the oral cavity: A focus on mucoadhesive. PDA J. Pharm. Sci. Technol. 2012; 66:466-500.

65. Hanif M, Zaman M. Thiolation of arabinoxylan and its application in the fabrication of controlled release mucoadhesive oral films. DARU Journal of Pharmaceutical sciences. 2017 Dec; 25:1-3.

66. Zaman M, Hanif M, Shaheryar ZA. Development of Tizanidine HCl-Meloxicam loaded mucoadhesive buccal films: In-vitro and in-vivo evaluation. PloS one. 2018 Mar 22;13(3):e0194410.

67. Zaman M, Hanif M, Qaiser AA. Effect of polymer and plasticizer on thin polymeric buccal films of meloxicam designed by using central composite rotatable design. Acta Pol Pharm. 2016 Sep 1;73(5):1351-60.

68. Mishra R, Amin A. Manufacturing techniques of orally dissolving films. Pharmaceutical Technology. 2011 Jan 2;35(1):70-3.

69. Zaman M, Hanif M, Sultana K. Synthesis of thiolated arabinoxylan and its application as sustained release mucoadhesive film former. Biomedical Materials. 2018 Feb 8;13(2):025019.

70. Zaman M, Hanif M, Khan MA. Arabinoxylan-based mucoadhesive oral films of tizanidine HCL designed and optimized using central composite rotatable design. Polymer-Plastics Technology and Engineering. 2018 Mar 24;57(5):471-83.

71. Zaman M, Hassan R, Razzaq S, Mahmood A, Amjad MW, Raja MA, Qaisar AA, Majeed A, Hanif M, Tahir RA. Fabrication of polyvinyl alcohol based fast dissolving oral strips of sumatriptan succinate and metoclopramide HCL. Science Progress. 2020 Oct;103(4):0036850420964302.

72. Kathpalia H, Patil A. Formulation and Evaluation of Orally Disintegrating Films of Levocetirizine Dihydrochloride. Indian Journal of Pharmaceutical Sciences. 2017 Mar 1;79(2).

73. Reza KH, Chakraborty P. Recent industrial development in oral thin film technology: An overview. PharmaTutor. 2016;4(8):17-22.

74. Schruben DL, Gonzalez P. Dispersity improvement in solvent casting particle/polymer composite. Polymer Engineering & Science. 2000 Jan;40(1):139-42.

75. Verma S. A review on conventional and modern techniques to develop Orodispersible films. Asian Journal of Pharmaceutics (AJP). 2018 Aug 18;12(02).

76. Tsujimoto, T. Solvent Casting Process. Google Patent 7,361,295, 22 April 2008.

77. Nagaraju T, Gowthami R, Rajashekar M, Sandeep S, Mallesham M, Sathish D, Shravan Kumar Y. Comprehensive review on oral disintegrating films. Current drug delivery. 2013 Feb 1;10(1):96-108.

78. Zaman M, Hanif M. In vitro and ex vivo assessment of hydrophilic polymer‐and plasticizer‐based thin buccal films designed by using central composite rotatable design for the delivery of meloxicam. Advances in Polymer Technology. 2018 Oct;37(6):1823-36.

79. Melegari C. Study of different technologies for film coating of drug layered pellets using ethylcellulose as functional polymer.

80. Maniruzzaman M, Boateng JS, Snowden MJ, Douroumis D. A review of hot-melt extrusion: process technology to pharmaceutical products. International Scholarly Research Notices. 2012;2012.

81. Barnhart SD. Thin film oral dosage forms. InModified-release drug delivery technology 2008 May 28 (pp. 235-256). CRC Press.

82. Palem CR, Kumar Battu S, Maddineni S, Gannu R, Repka MA, Yamsani MR. Oral transmucosal delivery of domperidone from immediate release films produced via hot-melt extrusion technology. Pharmaceutical development and technology. 2013 Feb 1;18(1):186-95.

83. McGinity, J.W.; Koleng, J.; Repka, M.; Zhang, F. Hot-melt extrusion technology. Encycl. Pharm. Technol. 2007, 19, 203–226.

84. Patil, H., Tiwari, R.V. and Repka, M.A., 2016. Hot-melt extrusion: from theory to application in pharmaceutical formulation. Aaps Pharmscitech, 17, pp.20-42.

85. Simões MF, Pinto RM, Simões S. Hot-melt extrusion in the pharmaceutical industry: toward filing a new drug application. Drug Discovery Today. 2019 Sep 1;24(9):1749-68.

86. Tumuluri VS, Kemper MS, Lewis IR, Prodduturi S, Majumdar S, Avery BA, Repka MA. Off-line and on-line measurements of drug-loaded hot-melt extruded films using Raman spectroscopy. International journal of pharmaceutics. 2008 Jun 5;357(1-2):77-84.

87. Arya A, Chandra A, Sharma V, Pathak K. Fast dissolving oral films: an innovative drug delivery system and dosage form. International Journal of ChemTech Research. 2010 Jan 1;2(1):576-83.

88. Yang, R.K.; Fuisz, R.C.; Myers, G.L.; Fuisz, J.M. Thin Film with Non-Self-Aggregating Uniform Heterogeneity and Drug Delivery Systems Made Therefrom. Google Patent 7,425,292, 16 September 2008.

89. Jamróz W, Szafraniec J, Kurek M, Jachowicz R. 3D printing in pharmaceutical and medical applications–recent achievements and challenges. Pharmaceutical research. 2018 Sep; 35:1-22.

90. Annaji M, Ramesh S, Poudel I, Govindarajulu M, Arnold RD, Dhanasekaran M, Babu RJ. Application of extrusion-based 3D printed dosage forms in the treatment of chronic diseases. Journal of Pharmaceutical Sciences. 2020 Dec 1;109(12):3551-68.

91. Łyszczarz E, Brniak W, Szafraniec-Szczęsny J, Majka TM, Majda D, Zych M, Pielichowski K, Jachowicz R. The impact of the preparation method on the properties of orodispersible films with aripiprazole: Electrospinning vs. casting and 3D printing methods. Pharmaceutics. 2021 Jul 22;13(8):1122.

92. Frey, Film Strips and Pharmaceuticals, Pharmaceutical Manufacturing and Packaging Sources, 2006; pp: 92-93.

93. Chaudhary H, Gauri S, Rathee P, Kumar V. Development and optimization of fast dissolving oro-dispersible films of granisetron HCl using Box–Behnken statistical design. Bulletin of Faculty of Pharmacy, Cairo University. 2013 Dec 1;51(2):193-201.

94. Bhyan B, Jangra S, Kaur M, Singh H. Orally fast dissolving films: innovations in formulation and technology. Int J Pharm Sci Rev Res. 2011 Jul;9(2):9-15.

95. Bai GE, Armenante PM, Plank RV, Gentzler M, Ford K, Harmon P. Hydrodynamic investigation of USP dissolution test apparatus II. Journal of Pharmaceutical sciences. 2007 Sep 1;96(9):2327-49.

96. Raju S, Reddy PS, Kumar VA, Deepthi A, Reddy KS, Reddy PM. Flash release oral films of metoclopramide hydrochloride for pediatric use: Formulation and in-vitro evaluation. J. Chem. Pharm. Res. 2011;3(4):636-46.

97. Patel RS, Poddar SS. Development and characterization of mucoadhesive buccal patches of salbutamol sulphate. Current drug delivery. 2009 Jan 1;6(1):140-4.

98. Yellanki SK, Jagtap S, Masareddy R. Dissofilm: a novel approach for delivery of phenobarbital; design and characterization. Journal of Young Pharmacists. 2011 Jul 1;3(3):181-8.

99. Gorle AP, Gattani SG. Design and evaluation of polymeric ocular drug delivery system. Chemical and Pharmaceutical Bulletin. 2009 Sep 1;57(9):914-9.

100. Patil PC, Shrivastava SK, Vaidehi S, Ashwini P. Oral fast dissolving drug delivery system: a modern approach for patient compliance. International journal of drug regulatory affairs. 2014 Jun 1;2(2):49-60.

101. Siqueira Jr WL, Nicolau J. Stimulated whole saliva components in children with Down syndrome. Special Care in Dentistry. 2002 Nov;22(6):226-30.

102. Pein, M.; Eckert, C.; Preis, M.; Breitkreutz, J. Taste Sensing System αAstree as Analytical Tool—Performance Qualification Using Caffeine Citrate as Model Substance. In Proceedings of the 8th Pharmaceutics & Biopharmaceutics World Meeting, Istanbul, Turkey, 19–22 March 2012.

103. Zaman M, Hanif M, Amjad MW, Mahmood A, Shah S, Raja MA, Rasool S, Sarfraz RM. Development of thiomer based buccal films for the enhancement of bioavailability: An in-vivo analysis. Pak. J. Pharm. Sci. 2019 Mar 1;32(2):759-64.

104. Zaman M. Formulation and Evaluation of Tizanidine-Meloxicam Mucoadhesive Buccal Films by Central Composite Rotatable Design and Their Pharmacokinetic Studies (Doctoral dissertation, Bahauddin Zakariya University Multan).

105. Zaman M, Hanif M, Murtaza H. Development and validation of RP-HPLC method for simultaneous estimation of tizanidine HCl and meloxicam in bilayer mucoadhesive buccal films. Acta Poloniae Pharmaceutica-Drug Research. 2018 Aug 31;75(4):851-9.

106. El-Setouhy DA, El-Malak NS. Formulation of a novel tianeptine sodium orodispersible film. Aaps Pharmscitech. 2010 Sep; 11:1018-25.

107. Anwar S, Zaman M, Raja MA, Mahmood A, Amjad MW. Rosuvastatin, Perindopril and Ezetimibe loaded instant release buccal films: Development and in vitro characterization. Journal of Applied Biomedicine. 2020 Oct 1;18(4).

108. Peh KK, Wong CF. Polymeric films as vehicle for buccal delivery: swelling, mechanical, and bioadhesive properties. J Pharm Pharm Sci. 1999 Aug;2(2):53-61.

109. Aburahma MH, Mahmoud AA. Biodegradable ocular inserts for sustained delivery of brimonidine tartarate: preparation and in vitro/in vivo evaluation. Aaps Pharmscitech. 2011 Dec;12:1335-47.

110. Baranowski P, Karolewicz B, Gajda M, Pluta J. Ophthalmic drug dosage forms: characterisation and research methods. The Scientific World Journal. 2014 Jan 1;2014.

111. Eroğlu H, Sargon MF, Öner L. Chitosan formulations for steroid delivery: effect of formulation variables on in vitro characteristics. Drug development and industrial pharmacy. 2007 Jan 1;33(3):265-71.

112. Kunte S, Tandale P. Fast dissolving strips: A novel approach for the delivery of verapamil. Journal of pharmacy and bioallied sciences. 2010 Oct 1;2(4):325-8.

113. Chavan DU, Marques SM, Bhide PJ, Kumar L, Shirodkar RK. Rapidly dissolving felodipine nanoparticle strips-formulation using design of experiment and characterisation. Journal of Drug Delivery Science and Technology. 2020 Dec 1; 60:102053.

114. Preis M, Knop K, Breitkreutz J. Mechanical strength test for orodispersible and buccal films. International journal of pharmaceutics. 2014 Jan 30;461(1-2):22-9.

115. Morales JO, McConville JT. Manufacture and characterization of mucoadhesive buccal films. European Journal of Pharmaceutics and Biopharmaceutics. 2011 Feb 1;77(2):187-99.

116. Bhupinder B, Sarita J. Formulation and evaluation of fast dissolving sublingual films of Rizatriptan Benzoate. Int J Drug Dev Res. 2012 Jan;4(1):133-43.

117. Khalil YI. Preparation and characterization of montelukast sodium (SMLT) as a dual sustained release buccal strip. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2015;24(2):61-71.

118. Bonsu MA, Ofori-Kwakye K, Kipo SL, Boakye-Gyasi ME, Fosu MA. Development of oral dissolvable films of diclofenac sodium for osteoarthritis using Albizia and Khaya gums as hydrophilic film formers. Journal of drug delivery. 2016;2016.

119. S Alghamdi H, Svirskis D, R Bunt C, Swift S, D Rupenthal I. Azithromycin and Dexamethasone Loaded β-Glucan Films for the Treatment of Blepharitis. Drug Delivery Letters. 2016 Feb 1;6(1):22-9.

120. Koland M, Sandeep VP, Charyulu NR. Fast dissolving sublingual films of ondansetron hydrochloride: effect of additives on in vitro drug release and mucosal permeation. Journal of Young Pharmacists. 2010 Jul 1;2(3):216-22.

121. Wuzhu YA, Shifeng WE, Jun LI, Zhufeng YU. Determination of reduced Young's modulus of thin films using indentation test. Acta Metallurgica Sinica (English Letters). 2009 Dec 1;22(6):468-80.

122. Prabhu P, Malli R, Koland M, Vijaynarayana K, D’Souza U, Harish NM, Shastry CS, Charyulu RN. Formulation and evaluation of fast dissolving films of levocitirizine di hydrochloride. International journal of pharmaceutical investigation. 2011 Apr;1(2):99.

123. Gavaskar B, Kumar SV, Sharan G, Rao YM. Overview on fast dissolving films. International Journal of Pharmacy and Pharmaceutical Sciences. 2010;2(3):29-33.

124. rights are reserved by Ms A, Amin PM. Oral Film Technology: Challenges and Future Scope for Pharmaceutical Industry.

125. Sharma D, Kaur D, Verma S, Singh D, Singh M, Singh G, Garg R. Fast dissolving oral films technology: A recent trend for an innovative oral drug delivery system. International Journal of Drug Delivery. 2015 Oct 12;7(2):60-75.

126. Gupta MS, Kumar TP, Gowda DV, Rosenholm JM. Orodispersible films: Conception to quality by design. Advanced drug delivery reviews. 2021 Nov 1; 178:113983.

127. Hoffmann EM, Breitenbach A, Breitkreutz J. Advances in orodispersible films for drug delivery. Expert opinion on drug delivery. 2011 Mar 1;8(3):299-316.

128. Panda BP, Dey NS, Rao ME. Development of innovative orally fast disintegrating film dosage forms: a review. International Journal of Pharmaceutical Sciences and Nanotechnology. 2012 Jul;5(2):1666-74.

129. Nahum V, Domb AJ. Recent developments in solid lipid microparticles for food ingredients delivery. Foods. 2021 Feb 11;10(2):400.

130. Arora L, Chakraborty T. A review on new generation orodispersible films and its novel approaches. Indo Am. J. Pharm. Res. 2017 Jan; 7:7451-70

131. Firoz Shaik, Padmini Karnatham, Rishmitha Dugganpalli, Swarnalatha Panga, Lakshmi Prasanna Akepati. Development and Pharmaceutical Evaluation of Sacubitril sodium Loaded oral fast Dissolving Films. Research J. Pharm. and Tech. 2020; 13(8):3553-3558.

132. Aditya Singh, Vaseem A. Ansari, Md Faheem Haider, Farogh Ahsan, Tariq Mahmood, Shubhrat Maheshwari, Ritesh Kumar Tiwari. Oral Fast Dissolving Film: The Avant-garde Avenue for oral Consignment Modus Operandi. Research Journal of Pharmacy and Technology. 2021; 14(4):2145-2.

133. S.B. Gondkar, Namrata D. Patil, R.B. Saudagar. Fast Dissolving Oral Films. Asian J. Pharm. Res. 6(1): January -March, 2016; Page 56-58.

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

135. Chonkar Ankita D., Bhagawati S. T., Udupa N.. An Overview on Fast Dissolving Oral Films. Asian J. Pharm. Tech. 2015; 5( 3); 129-137.

136. Supriya, B. Lakshmi, K. Padmalatha. Formulation Development and In- Vitro Evaluation of Fast Dissolving Oral Films containing Ranitidine Hydrochloride. Asian J. Pharm. Tech. 2021; 11(1):13-17.

137. Y. Raja Jayarao, D. Deborah, T. Ambedkar, S. Manohar Babu. Formulation and Evaluation of Fast Dissolving Oral Films of Perindopril. Res. J. Pharm. Dosage Form. and Tech. 6(2): April- June 2014; Page 71-80.

138. Sara Sadique, Ramya Sri S. Preparation and Evaluation of Fast Dissolving Oral Film of Losartan Potassium. Res. J. Pharma. Dosage Forms and Tech.2020; 12(1): 13-16.

139. A. Srinivas, D.V.R.N. Bhikshapathi. Fast Dissolving Oral Films of Pramipexole HCl monohydrate: Preparation and in vitro evaluation. Research J. Pharm. and Tech. 2018; 11(3): 1001-1008.

140. Kamma Keerthi Sai. Formulation Development and In vitro Evaluation of Memantine Hydrochloride Fast Dissolving Oral Films employing different grades of Hydroxy Propyl Methyl Cellulose. Research Journal of Pharmacy and Technology. 2022; 15(1):17-3.

141. T. Anusha, R. Swetha Sri. Derivative UV Spectroscopic Cleaning Method Development and Validation of Darunavir API incorporated into Dissolving Oral Film. Research Journal of Science and Technology. 2024; 16(2):107-4.

Received on 24.07.2024 Revised on 19.11.2024

Accepted on 15.02.2025 Published on 09.05.2025

Available online from May 12, 2025

Res. J. Pharma. Dosage Forms and Tech.2025; 17(2):149-163.

DOI: 10.52711/0975-4377.2025.00022

This work is licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 International License. Creative Commons License.

Brand Name	API	OFDF Use	Category	Reference
Risperidon hexal	Risperidone	For treating schizophrenia	R x	1
Gas-X Thin Strips	Simethicone	For reducing bloating	O T C	10
Chloraseptic Sore Throat Relief Strips	Benzocaine	For sore throat relief	O T C	15
Orajel Kids Sore Throat Relief Strips	Benzocaine	For children’s sore throat relief	O T C	16
Snoreeze Oral Strips	Peppermint oil, vitamin E	For snoring relief	O T C	16
Benadryl Allergy quick dissolve strip	Diphenhydramine HCL	For allergy	O T C	16
Pedia-Lax Quick Dissolve Strip	Sennosides	For treating constipation	O T C	17
Supress Cough Strips	Menthol	For cough	O T C	18
Sudafed PE	Phenylephrine HCL	For relief of stuffy nose	O T C	19
Theraflu Thin Strips multi symptom	Diphenhydramine HCL	For the common cold	O T C	18
Zuplenz	Ondansetron	For nausea and vomiting	R x	16
NiQuitin	Nicotine	For nicotine withdrawal symptoms	R x	19
Zolmitriptan oral film	Zolmitriptan	For migraine	R x	19
Sildenafil Sandoz Orodispersible Film	Sildenafil	For treating erectile dysfunction	R x	20
IvyFilm	Hedera helix extract	For relief of productive cough	O T C	20
Clobazam OSF	Clobazam	Used to treat seizures	R x	20

Property/sub type	Flash release wafer	Mucoadhesive melt- away wafer	Mucoadhesive sustained release wafer
Area (cm2)	2-8	2-7	2-4
Thickness (mm)	20-70	50-500	50-250
Structure	Single layer	Single and multilayer system	Multilayer system
Excipient	Soluble, highly hydrophilic polymer	Soluble, hydrophilic polymers	Low/non-soluble polymers
Drug phase	Solid solution	Solid solution or suspended drug particles	Suspension and/or solid solution
Application	Tongue (upper palate)	Gingival or buccal Region	Gingival, (another region in the oral cavity)
Dissolution	Maximum 60 seconds	Disintegration in a few minutes, forming gel	Maximum 8-10 hours
Site of action	Systemic or local	Systemic or local	Systemic or local

Drug	Drug class	BCS class	Dose (mg)	Category
Chlorpheniramine	Antihistamine	1	4-12	OTC
Loratadine	Antihistamine	1	5-10	OTC
Diphenhydramine	Antihistamine	1	12.5–60	Rx
Dextromethorphan	Antitussives	2	10-30	OTC
Sildenafil	PDE inhibitors	1	25-100	Rx
Ketoprofen	NSAID	2	12.5-25	OTC
Sumatriptan	SSRA	3	35-70	Rx
Zolmitriptan	SSRA	3	2.5	Rx
Loperamide	ANTIDIARRHEAL	2	2	OTC
Famotidine H2	H2 blockers	3	5-10	Rx
Nicotine	NCA	1	1-15	Rx
Pseudoephedrine	Nasal decongestants	1	15-60	OTC
Atorvastatin	HMG-CoA	2	5-80	Rx
Valdecoxib	Cox-2 inhibitor	2	5-20	Rx
Amlodipine	CCB	1	2.5-10	Rx
Rofecoxib	NSAID	2	5-25	Rx
Setraline	SSRI	2	10-100	Rx
Ziprasidone	Antipsychotics	2	20-80	Rx
Eletriptan	SSRI	1	10-40	Rx
Nitroglycerin	Vasodilators		0.3-0.6	Rx
Phenylephrine	Antihistamine		5-10	OTC

Excipient	Role of excipient	Example of excipient
Film-forming polymers	They provide shape, elasticity, fast disintegration, and mechanical strength in films	Sodium carboxy methyl cellulose, hydroxyl ethyl cellulose, hydroxyl propyl methyl cellulose, pectin, pullulan, gelatin, sodium alginate, starch, maltodextrin, methacrylic acid, xanthan gum, guar gum, locust bean gum, carrageenan, chitosan, polyvinyl pyrrolidone, polyvinyl alcohol, polyethylene oxide, polyvinyl acetate, polyvinyl pyrrolidone
Plasticizers	They provide elongation, tensile strength, and plasticity; improve absorption and solubility; prevent crushing; and reduce brittleness and glass transition temperature	Mannitol, glycerol, sorbitol, citric acid macrogol, propylene glycol, polyethylene glycols, phthalate derivatives (dibutyl, diethyl, dimethyl), citrate derivatives (triacetin, acetyl citrate, triethyl, tributyl)
Sweetening agents	They are used to improve the taste of films for patient compliance	Glucose, fructose, sucrose, sucralose, maltose, sorbitol, mannitol, stevioside sodium, ribose, cyclamate salts, aspartame, thaumatin, xylose, ribose, flavored essences, cyclamate, oleoresins
Saliva stimulants	They increase saliva production	Ascorbic acid, citric acid, tartaric acid, malic acid, lactic acid
Taste maskers	They are used to mask nauseating and bitter tastes for patient compliance	Hydroxypropyl-β-cyclodextrin, maltodextrin, sulfobutylether-β-cyclodextrin
Surfactants	They help to disintegrate films in seconds and allow dispersion and solubilization	Poloxamer, sodium lauryl sulfate, polysorbate, laureth-a, sucrose esters, dodecyl maltoside, cetyl trimethylammonium bromide