Shivajirao pawar college of pharmacy pachegaon
Buccal films have transformed oral drug delivery, offering enhanced bioavailability, rapid absorption, and improved patient compliance. The oral cavity’s mucosal membrane presents an attractive route for systemic and local therapy, leveraging the ease of administration and patient-centric benefits of oro-mucosal drug delivery. This comprehensive review discusses – Benefits and drawbacks of buccal drug delivery, Anatomical and physiological aspects of oral mucosa, In vitro techniques for examining buccal drug delivery systems, Key excipients are highlighted, including- Polymers for controlled release, Permeation enhancers for improved absorption, Carriers for targeted drug delivery. The review also explores- Manufacturing technologies: solvent casting, hot melt extrusion, and 3D printing, Future challenges and opportunities in buccal film development, Historical context and current commercial marketplace. By addressing the complexities of buccal drug delivery, this review provides a roadmap for researchers, clinicians, and industry experts, underscoring the transformative potential of buccal films.
The buccal region, comprising the mucosal membrane lining the oral cavity, has emerged as a
promising site for targeted drug delivery. Offering a unique combination of local and systemic
effects, buccal delivery provides an attractive alternative to traditional oral drug administration.
This route leverages the mucosa’s high vascularization, reduced enzymatic activity, and minimal sensitivity to enhance bioavailability, minimize dose-related effects, and improve patient adherence. Buccal drug delivery is particularly suited for potent drugs requiring rapid clinical response and extended therapeutic effects, making it an ideal option for acute conditions.
(1) The buccal mucosa, a complex and dynamic tissue, poses significant
challenges in developing effective in vitro models for mucoadhesive buccal film evaluation. Patient variability, spanning pediatric to geriatric populations, with diverse disease statuses and multi-morbidities, complicates the development of a universal in vitro methodology. The lack of standardized In vitro models, coupled with the availability of alternative dosage forms (e.g., solutions, syrups) for specialized populations, has hindered the commercialization of mucoadhesive film technology. (2) Compared to oral delivery, the buccal route provides faster onset of action and improved bioavailability due to – High blood flow, Reduced enzymatic activity, Bypassed first-pass metabolism ,Minimized acidic degradation and food interactions . Various dosage forms, including muco-adhesive films, have been developed to exploit this non-invasive route. (3) The buccal route of administration offers a promising alternative to oral and intravenous routes, providing direct access to the systemic circulation. The buccal mucosa, located on the inner side of the cheeks, is a non-keratinized tissue conducive to drug absorption. The buccal mucosa's unique characteristics make it suitable for drug delivery. Non-keratinized tissue, Elastic and penetrable, Stratified epithelium with 40-50 cell layers, Thickness is 400-700 mm, Surface area is ?50 cm?2;.Drug absorption across the buccal mucosa depends on- Physicochemical properties of the molecule, Interaction with cell plasma membranes ,Dosage form.
(4) Various routes administer drugs into the body, including oral, parenteral, transdermal, and sub-mucosal . The oral route is the most widely accepted due to its low therapy cost, comfort, and self-medication capabilities . Over 70% of marketed drugs are oral dosage forms, driven by patient preference and adaptability . However, approximately 50% of the population, particularly pediatric and elderly patients, struggle with solid oral preparations
due to choking hazards, leading to non-compliance .Recent advances in novel drug delivery systems aim to enhance safety and effectiveness by developing convenient and patient-compliant dosage forms . Modifications in oral drug delivery have led to the evolution of Altered release tablets/capsules, Oral dispersible tablets, Fast mouth-dissolving films (MDFs) MDFs rapidly dissolve in the oral cavity without water, ideal for patients with swallowing difficulties . By incorporating oral mucosal permeation enhancers, MDFs deliver drugs systemically, bypassing gastrointestinal tract and first-pass metabolism .(5)
The development of Innovative drug delivery systems has focused on overcoming the limitations of traditional administration routes. Recently, the oral mucosa, particularly the buccal and sublingual mucosa, has garnered significant attention for drug administration. The buccal route offers- Direct access to systemic circulation via the internal jugular vein, Bypassing hepatic first-pass metabolism, Reduced side effects. However, buccal delivery faces challenges-Low permeability, Smaller absorptive surface area compared to the small intestine . Advances in drug delivery technology emphasize, Pharmacokinetic profile optimization, Targeted drug delivery. Nanotechnology emerges as a promising approach for buccal drug delivery. Nano-carriers offer- Enhanced bioavailability, Prolonged systemic circulation, Controlled drug release, Steady-state plasma concentration ,Reduced side effects.(6)
Anatomy and physiology of Buccal Mucosa :
The buccal mucosa, like the skin, serves the fundamental function of shielding underlying structures from external substances. A stratified squamous epithelium makes up the buccal mucosa’s surface, and an undulating foundation membrane divides it from the lamina propria and submucosa, the underlying connective tissue . The keratinocytes that make up this stratified squamous epithelium are developing layers of cells that undergo size, shape, and content changes as they move from the basal region to the superficial region, where the cells are shed.(7)
Epithelium: The epithelium is made up of roughly 40–50 layers of 500–800 ?m thick stratified squamous epithelial cells. Connective tissue and the basement membrane The basement membrane (BM), a continuous layer of extracellular materials, separates the connective tissues from the basal layer of epithelium. Although some macromolecules and complexes may have their mobility restricted by connective tissue and the basement membrane, these two zones are thought to have little effect on the diffusion of the majority of substances of therapeutic interest.(8) The mouth cavity is approximately 100 cm?2;. The buccal surface makes up around one-third of this, and it is lined with an epithelium that is roughly 0.5 mm thick . The lipid makeup of the cells in the keratinized and non-keratinized areas of the oral epithelium varies from one another. The keratinized epithelium is primarily composed of neutral lipids, such as ceramides, but the non-keratinized epithelium has a small number of polar lipids, namely glucosylceramides 2 and cholesterol sulphate. A further obstacle to medication diffusion over the buccal membrane is the abundance of elastic fibers in the dermis of the membrane. A medication that gets beyond this membrane enters the systemic circulation through an artery and capillary network. The lymphatic drainage enters the jugular ducts and nearly parallels the venous vascularization. Saliva (about 0.5 to 2 liters per day) continuously washes the mouth mucosal area. The non-keratinized areas of the oral mucosa are where drugs are absorbed for the delivery of proteins and peptides. Compared to other mucosal channels such as the nasal, vaginal, rectal, etc., the buccal route has clear advantages. (9).
Fig. No. 1 Structure of oral cavity showing the parts of oral cavity.
Fig. No.2 Cross section of buccal epithelial cells , showing keratinized and non -keratinized epithelium.
Bio adhesion Theories and Mechanism :
The mechanism of bioadhesion is as follows: Mucus penetrates the bioadhesive’s chain several times, causing low chemical bonds to settle; the expansion of the sticky material and chemical connections caused by electrostatic contact, hydrophobic interaction, hydrogen bonding, and dispersion forces are the main causes of the bonding between mucus and the biological substance. A good wetting of the bioadhesive and the membrane or the bioadhesive swelling will result in intimate contact between the two.(10) The oral mucosa can be penetrated by two different routes for passive drug transport: paracellular and transcellular. These two pathways can be used simultaneously by permeabilants, however one is typically chosen over the other based on the diffusant’s physicochemical characteristics. Because the cytoplasm and intercellular gaps are hydrophilic, lipophilic substances would be poorly soluble in these environments. However, because the cell membrane is very lipophilic, hydrophilic solutes will find it difficult to pass through the cell.(11) Contact stage: Close contact (wetting) between the mucus (membrane) and the mucoadhesive membrane is caused by both a fair wetting of the bioadhesive and the swelling of the bioadhesive. Consolidation stage: Hydrophobic and hydrogen bonding dispersion forces are examples of physicochemical interactions that aid in strengthening and consolidating the adhesive junction, which prolongs adherence.(9)
Concepts of Bioadhesion :
1.Electronic Theory :
The electronic theory predicts that a double layer of electrical charge will arise at the bioadhesive interface as a result of electron transfer upon contact between the bioadhesive polymer and the glycoprotein, which have distinct electronic structures that rotate.
2. Adsorption Theory :
Bioadhesive systems stick to tissue because to Vander walls hydrogen bonding and related forces, according to the adsorption theory.
3. Wetting Theory :
For a strong adhesive connection to form, close molecular contact is necessary, necessitating analysis of the bioadhesive candidate material’s wetting equilibrium and dynamic behaviour with the mucus. The following are some essential properties of liquid bioadhesive materials:
4. Diffusion Theory :
The creation of an extremely deep layer of chains may result from the interpenetration of mucus and polymer chains. Diffusion occurs when two polymers or fragments of the same polymer come into intimate contact. When the polymer molecules and the dangling chains of the glycoprotein network come into close contact, this is known as chain interpenetration. Because of the concentration gradient, the speeds at which the bioadhesive polymer chains perforate rely on the chemical potential gradient and the diffusion coefficient of a macromolecule across a cross-linked network. For bioadhesion to occur during integration, the bioadhesive medium must be well soluble in the mucus. Therefore The discrepancy between the bioadhesive medium’s and the glycoprotein’s solubility characteristics has to be as close to zero as feasible.
5.Fracture Theory :
Adhesion is equivalent to the disunion of two surfaces following adhesion, according to the fracture hypothesis of adhesion. The fracture vigor and adhesive vigor are equivalent, as indicated by the formula G = (E?. /L) ½. Where E stands for Young’s elasticity module. ? stands for fracture energy. The critical crack length (L) is the distance between two surfaces(12).
Factors affecting mucoadhesion :
Factors connected to the active polymer:
A number of the polymer’s attributes are essential for mucoadhesion. These include concentration, swelling, polymer molecular weight, specific confirmation, and the flexibility of polymer chains, all of which might impact mucoadhesion.
Environmental factors: Mucoadhesion can be affected by functional strength, first contact time, and the pH of the polymer-substrate interface.
physiological factors: These factors can also impact mucoadhesion are disease status and mucin turnover.(13)
Advantages:
Disadvantages:
1.The oral cavity’s membranes have a total surface area of 170 cm2, of which about 50 cm2 is made up of non-keratinized tissues, such as the buccal membrane. This is known as the limited absorption area.
2. Mucosal barrier characteristics.
3. The medicine is thereafter diluted due to the constant release of saliva (0.5-2 l/day).
4. There is a risk that someone could choke if they unintentionally swallow the delivery system.
5. The loss of dissolved or suspended medication and, eventually, the involuntary removal of the dose form can also result from swallowing saliva.(14)
Ideal Characteristics of mucoadhesive Buccal Films :
Formulation aspect:
Drug Substance:
Prior to developing mucoadhesive drug delivery systems, it is necessary to determine whether a rapid or protracted release and a local or systemic effect are the desired outcomes. When choosing a medication to use in the design of buccoadhesive drug delivery systems, pharmacokinetic characteristics are crucial. The following traits should be present in the medication . Traditionally, a single dose of the medication should be extremely little. For regulated drug delivery, medications with a biological half-life of two to eight hours make good choices. When the medication is taken orally, its T max exhibits numerous fluctuations or greater values. When used orally, the medicine should be absorbed passively; it may have a first-pass effect or pre systemic drug elimination. (16)
Polymer:
The Initial phase in crafting buccoadhesive dosage forms involves carefully choosing and characterizing. Utilize suitable bio adhesive polymers when formulating. Biomedical adhesive polymers play a significant part in. Drug delivery systems involving the use of buccoadhesive formulations for administering medications. Polymers are utilized in matrix devices for drug delivery purposes. The drug release duration is controlled by the polymer matrix in which it is embedded. Polymers with bioadhesive properties .They belong to a highly diverse class and offer significant benefits to patient health care and treatment. The drug is delivered to the mucous membrane through a layer that controls the release rate or a central layer. Revise this text in a smoother style: Biography Adhesive polymers that stick to the mucin/epithelial surface are highly effective and result in substantial outcomes .Enhancements have been made in the field of oral drug administration.(17)
Fig. No. 3 Oro dispersible thin Buccal films
Plasticizer:
When creating a buccal medication delivery system, plasticizers are essential . They aid by enhancing the buccal film’s mechanical qualities, such as its tensile strength and elongation, and they also offer additional benefits like decreased brittleness and increased flexibility, as well as an improvement in the polymer’s flow characteristics and a reduction in the glass transition temperature. It is possible to modify the amount of polymer utilized, which will change the resulting film’s characteristics. Glycerin, sorbitol, propylene glycol, polyethylene glycol, tri-acetin, dibutyl phthalate, tri-ethyl-citrate, acetyl tri-ethyl-citrate, and various citrate esters are a few examples of plasticizers. The quantity of plasticizer that to be used can range from around 0 to 20%W/W. ((18)
Sweetning agents:
Sweeteners are now essential excipients in systems that administer medications orally. The formulation’s pleasant taste is very important when it comes to the paediatric population. The mouth-feel of mouth-dissolving formulations is improved by the inclusion of both natural and artificial sweeteners. Natural sweeteners include lactose, sucrose, dextrose, fructose, glucose, and liquid glucose. The sweetness of fructose is better absorbed by the mouth more rapidly than that of sucrose and dextrose. It is recommended to use artificial sweeteners if the dosage form is meant for diabetics. Among the first generation of artificial sweeteners are aspartame, cyclamate, and saccharin. The second generation comprises neotame, alitame, sucralose, and acesulfame-K.(19)
Flavouring agents:
To enhance the flavour and create a pleasing sensory experience, flavouring chemicals are used. They may consist of natural or synthetic flavours like fruit flavours, mint, or other appropriate taste-masking substances(20).
Surfactant:
In the film, surfactants are employed as wetting agents or solvents. When surfactants are utilized, the film releases the medication instantly after dissolving quickly in the buccal mucosa in a matter of seconds. Drugs that are poorly soluble in the oral cavity may become more soluble when surfactants are used .(21)
Penetration Enhancers :
By employing penetration enhancers, medication penetration via the buccal mucosa was improved. One of the simple penetration enhancer examples is the use of water; they should have reversible and non-irritating effects. Chemicals that may enhance penetration include terpenes (like eucalyptus), fatty acids (like oleic acid), solvents (like ethanol), and surfactants (like Tween). Furthermore, polymers possessing the mucoadhesion feature, bile salts, azone, and currently chitosan and its derivatives, have the capacity to enhance penetration. Chitosan is thought to be a potential transmucosal absorption enhancer for hydrophilic macromolecular medications (22)
Saliva stimulating agent :
salivary stimulants can be made from acids used in meal preparation. Saliva stimulating compounds are used to speed up the production of saliva, which will help the formulations of rapid dissolving films dissolve more quickly. Salivary stimulants include lactic acid, ascorbic acid, tartaric acid, malic acid, and citric acid, with citric acid being the most popular. Between 2 and 6% of the film’s weight is made up of these agents, either alone or in combination.(23)
Backing membrane : To avoid needless drug loss from all sides of the device, the backing membrane should be impermeable to both the drug and mucus. Inert, insoluble, or poorly soluble in water materials should be employed to produce the backing membrane. The following materials are frequently used in backing membranes: polycarbophil, sodium alginate, carbopol, ethyl cellulose, and HPMC.(24)
Colouring agents :
It is preferred that Buccal film contain no more than 1%w/w of FD&C-approved colouring additives. Titanium dioxide, for instance. (25)
Method of preparation :
Solvent Casting method:
Fig. No. 4 Solvent Casting method of preparation of buccal films.
The necessary amount of polymer is introduced and dissolved in distilled water in the solvent casting procedure. This solution contains a small amount of an active medicinal component. After adding plasticizer to the solution, it is well agitated. After casting the solution onto a petridish, it is dried at 400C in a hot air oven. Using a blade, remove it off the petriplate once it has dried, then leave it in the desiccator for a full day. Cut in the appropriate size and shape from now on.
The Solvent Casting Method’s steps Step 1: Making the casting solution.
Step 2: Deaeration of the mixture .
Step 3: Fill the mold with the proper amount of solution.
Step 4: The casting solution is dried .
Step 5: Cutting the final dose form so that the appropriate amount of medication is contained. (26)
Solid dispersion method:
Solid dispersion is the process of dispersing one or more active substances in a solid form while ancephous hydrophilic polymers are present. A liquid solvent dissolves the drug. After that, add this solution to a polyethylene glycol melt that is below 70°C. Using dies, the obtained solid dispersions are formed into films.(27)
Direct milling:
This method creates patches without the need for solvents. For motorized drug and excipient mixing without the presence of a liquid solution, direct milling or kneading techniques are employed. The resultant material is rolled to get the required thickness. After that, the backing material is laminated. Because there is no chance of leftover solvents or health problems caused by solvents, the solvent-free method is selected.(28)
Hot melt extrusion:
Granules, prolonged release tablets, and transdermal and transmucosal drug administration systems are frequently made via hot metal extrusion . As early as 1971, the pharmaceutical sector began using melt extrusion as a manufacturing tool. The medication is combined with solid carriers. The mixture is melted by an extruder with heating. Lastly, the dies form the melt into films.(29)
Fig. No. 5 Method of preparation of buccal films Hot melt extrusion
Evaluation techniques
In vivo methods
GI transit time:
By the use of radio-opaque It uses radio-opaque markers, like barium sulphate, that are contained in bioadhesive DDS to assess how bioadhesive polymers affect GI transit time. X-ray examination and faces collection (using an automated faces collection system) offer a non-invasive way to track the overall GI residence time without interfering with regular GI motility. To investigate the DDS’s transit through the GI system, mucoadhesive labelled with Cr-51, Tc-99m, In-113m, or I-123 have been employed.
Gamma scintigraphy:
The development of pharmacological dosage forms makes use of this useful instrument. It is feasible to get information non-invasively using this technology. Information about oral dose forms for the various GI tract areas is provided by this technique. The location and timing of dosage form disintegration, the site of drug absorption, and the impact of food, illness, and dosage form size on the dosage forms’ in vivo performance (30).
Swelling index:
The diameter approach was used to calculate the swelling index. 0.2 g of agar was dissolved in 10 mL of heated simulated saliva fluid with a pH of 6.8 (50–70 ?C) to create the agar solution. After that, the solution was transferred to a Petri dish and let to cool. Once the initial patch diameter was established, each patch was left to swell on its own gel surface. After two, five, and seven hours, the patch’s diameters were measured, and the average of the three readings was used to record the results. Since a 7-hour residence period was advised, swelling studies were conducted for 7 hours. Three improved formulations (PS1, PE1, and PH2) were the subjects of the observations. {(Df-Di) / Di}x 100 is the swelling index, where Di is the original patch diameter and Df = final patch diameter.
Folding stamina:
A sharp blade was used to cut three patches of each mixture that were larger in size, measuring 2 × 2 cm. A tiny strip of patch was folded repeatedly at the same spot until it broke in order to measure folding endurance. The folding endurance rating was determined by counting the number of times the patch could be folded in the same spot without breaking. The average value was determined and noted (31).
Percentage of moisture content :
The difference between the weights taken before the film was placed in the desiccators and after a certain amount of time is used to determine the film’s moisture content. After adding calcium chloride to the desiccators, the entire system is left for a full day. The percentage of moisture uptake is calculated using the following formula.
% Moisture content = (initial weight- final weight/final weight)×100
Absorption of moisture:
After being taken and weighed, the sample film is stored at room temperature in desiccators. The film is removed after 24 hours and exposed to 84% relative humidity. In desiccators, saturated potassium chloride solution is employed until a consistent weight is achieved. The percentage of moisture uptake is calculated using the formula below.
Absorption of moisture = ( final weight – initial weight/initial weight)×100 (32)
Test for palatability:
Palatability is a study that is carried out based on taste, followed by bitterness and appearance. Each batch is given an A, B, or C grade according to the criteria; a formulation is deemed average if it receives at least one A grade, good if it receives two A grades, and very good if it receives all three A grades. (33)
in vivo mucoadhesion time:
The Human Ethical Committee of Maharshi Markendeshwar University in Mullana, Ambala, India, gave its approval to this study. Healthy human volunteers (n = 6) gave their written agreement to conduct the study. Using a light force for 10 seconds, placebo films measuring 1 x 1 cm2 were cut and adhered to the volunteers’ upper cheek pouch. In order to prevent the film ends from abrasion, the volunteers were instructed not to consume any food or liquids during the trial. The films were observed for palatability, discomfort, residence time in the human buccal cavity, and irritation.
Ex vivo mucoadhesion/retention period:
Porcine cheek mucosa was used to measure the oral buccoadhesive films’ ex vivo mucoadhesion/retention time. Using double-sided sticky tape, a 2 cm2 porcine cheek pouch was cut and adhered to the beaker’s inside. After cutting the 1–2 cm2 film, a drop of PBS was added to moisten the surface. For ten seconds, films were applied to the porcine pouch’s surface using a light force. To replicate buccal conditions, 500 ml of PBS was added to the beaker, kept at 37 ± 1 C, and swirled at 150 rpm.
Ex vivo mucoadhesive strength ex vivo :
The produced films’ mucoadhesive strength was assessed using a TA-XTi texture analyser (Stable Micro Systems Ltd., Surrey, UK). Porcine cheek mucosa was used as the substrate to test mucoadhesive strength. After being examined for integrity, the cheek pouch was set up on the stationary platform. Using double-sided adhesive tape, a piece of film (about 1 to 2 cm2) that was to be evaluated was cut and affixed to the texture analyzer’s moving probe. To keep the pig cheek mucosa moist throughout the contact time, two millilitres of the buffer solution were added to the assembly. The texture analyzer’s moveable probe was lowered until it touched the mucosa. The twenty seconds passed during which the film and cheek mucosa came into touch. The pre-test speed was 0.5 mm/s, the test/post-test speed was 0.5 mm/s, and the applied force was 1 N. These parameters were used to get measurements. By measuring the greatest force produced during probe return, the mucoadhesive strength was determined. The mean ± SD was used to express the results, which were acquired in triplicate for each film.(34)
The weight of the film :
The buccal film Is weighed using an adjustable weighing balance, and each one’s weight has been calculated separately.
Thickness of film :
Since it significantly affects the film’s dosing accuracy and preserves the predictability of the production process, this test is conducted using a calibrated micrometre screw gauge to measure the uniformity of the film’s thickness. Following five evaluations of the film’s thickness, a mean value is determined.
Surface pH of the film :
The electrode can be placed on the surface of the film and allowed to equilibrate for one minute to determine the pH after the films have interacted with one millilitre of distilled water for two hours at 25 degrees Celsius. (35)
Mechanical Properties of the films:
Mechanical characteristics, tensile strength and elongation at break were estimated from the load time profiles of the films using INSTRON® tensile tester. The sample’s upper and lower grips, each measuring 5 cm by 1 cm, were fastened to the base plate and crosshead, respectively, such that the former was precisely 5 cm above the latter. The crosshead was raised at a rate of one centimetre per second. When the film broke, the elongation and force were measured. The mean (±SD) of five replicates was used to report the results. (36)
in vitro drug release:
Permeation through the buccal epithelium requires the drug to be released from the prepared films. The cumulative drug release from the formulation over a specified time period is ascertained via release studies. There is currently no specialized in vitro technique for studying the medication release of buccal films. Various researchers employ standard or modified dissolution apparatus with specific modifications or Franz diffusion cells (FDC) to study drug release from buccal films.(37)
Tensile strength:
The highest tension under which the film breaks is this. The polymeric film was pulled using a pulley system to measure the elongation as a tensile strength; weights were progressively added to the pan to increase the pulling force until the film broke. Using a magnifying glass, the film’s elongation was seen. The unit of measurement is kg/cm^2. The formula was used to determine the tensile strength. Where S stands for tensile strength, m for mass in grams, g for gravity-induced acceleration, b for width in centimeters, and t for thickness.(38)
Stability study :
Twenty people between the ages of 20 and 35 had their saliva collected and filtered as part of a laboratory stability research on patches. The films were placed in individual petri dishes with five milliliters of human saliva and baked for six hours at 37°C ± 0.2°C. Films were inspected for variations in colour, shape, collapse, and physical stability at regular intervals.(39)
Therapeutic applications :
Potential uses of mucoadhesive buccal films for therapeutic purposes There are numerous therapeutic and clinical opportunities where the mucoadhesive buccal film technology can be used to provide high-quality, safe, and effective therapy because of the broad range of applications for this technology. Shows the various medical conditions and therapeutic areas for which mucoadhesive buccal films have been developed. It is evident from the literature that mucoadhesive films are preferred for use in inflammatory and cardiovascular conditions, possibly to address the low oral bioavailability of beta-blockers like carvedilol and propranolol hydrochloride, which are caused by extensive hepatic first-pass metabolism. However, it’s also likely that the writers listed here are just proving that the mucoadhesive buccal film technology is feasible without taking into account the therapeutic region that the actual drug corresponds to.
Particular patient groups and mucoadhesive buccal films :
Because dysphagia and swallowing difficulties are common in pediatric and geriatric age groups, mucoadhesive buccal films offer a definite therapeutic benefit in these patient populations. The following conditions have been linked to this in the pediatric population: congenital abnormalities, iatrogenic problems, respiratory, cardiac, gastrointestinal, neurological, and caustic injuries. The developmental process also contributes to swallowing issues in this population, which leads to the usage of various dosage aids, such as an oral syringe. Most children between the ages of 6 and 11 could swallow a small oral pill, according to research by Ostrom, Meltzer, and Welch, whereas Bracken et al. showed that most children between the ages of 4 and 8 could successfully ingested tablets when they attempted to do so, while Ostrom, Meltzer, and Welch showed that the vast majority of children between the ages of 6 and 11 could take a small oral pill.
Personalized medication and mucoadhesive buccal films :
It is becoming increasingly apparent that traditional mass-produced dosage forms, including pills and capsules, are not as successful in treating patients as they may be. This is because patients differ from one another, dose strengths are rigid, and modifying drug dosages in oral-solid dosage forms (i.e., tablet splitting) is difficult. As a result, the current “one size fits all” approach to treatment is ineffective. This is supported by a 2016 UK National Health Service report that said that personalized medicine—treatment that is tailored to each patient’s unique therapeutic needs—is the way of the future.
Possibilities for developing nations :
Access to medications is a subject that has been extensively studied in the literature and affects roughly 33% of the world’s population. To influence the procurement and delivery of important medications at the national and local levels worldwide, the World Health Organization has released a list of critical medications for children under the age of twelve (350 total) and for adults over the age of forty-nine (479 total). Only two of the 829 medicines listed in this public material, however, are recommended for buccal administration, and they are both midazolam oro-mucosal solutions.
Patient-related variables impacting the formation of mucoadhesive films :
When creating new medications, the therapeutic needs of the patients should come first. There are usually more confusing elements that affect drug product performance that developers may be aware of or are prepared to fully investigate during the development process, even though this is frequently the case. Therefore, it is essential to consider patient physiology and the different elements that may affect physiological parameters while designing safe, high-quality, and effective dose forms. To boost the possibility of successful therapeutic outcomes, in addition to the effects of concurrent drugs and/or facilitators of patient acceptability.
Physiology of the mouth affecting buccal medication distribution :
Oral physiology can be carefully taken into account when developing dose forms that are found in the mouth. It can also help with general dosage form knowledge that can be shared with patients through patient information leaflets or healthcare providers. Due to the lengthy analysis of the basic overview of oral anatomy and oral physiology [25], this discussion will only cover the physiological features that have been determined to support buccal medication administration and the factors controlling these features.
The Impact of pathology on buccal drug delivery:
Since mucoadhesive buccal films are found in the oral cavity, conditions that impact the oral cavity will also affect how effective mucoadhesive buccal films are. One such instance is oral mucositis, for which a low salivary flow rate was thought to be a risk factor for individuals who were intended to undergo 5-fluorouracil as part of chemotherapy. Additionally, issues with the jugular vein would probably affect how well medications taken orally would be absorbed throughout the body. Incompetence of the internal jugular valve was determined to be the primary cause of slow blood flow, while hyperthyroidism patients and pregnant women saw increased turbulent flow. The carotid-cavernous fistula and arteriovenous malformation have been identified as the causes of pulsatile turbulent jugular venous flow.(40)
Limitations :
• It is not possible to deliver medications that are unstable at buccal pH
• The buccal membrane is generally less permeable than the sublingual membrane.
• This method cannot be used to give medications that irritate the mucosa or have an unpleasant or bitter taste.
• Only a little amount of the drug can be provided.
• This method can only be used to give medications that are absorbed by passive diffusion.
• Eating and drinking are restricted. •
The need for regular dosage may result from the flushing action of saliva or meal consumption.
• Only low-dose medications are appropriate. (41)
OTFs’/ Buccal films Prospects for the Future Market:
OTF has enormous commercial potential in the future. For example, according to a report titled “Market Research Future Report,” the global market for OTFs is expected to grow at a “Compound Annual Growth Rate” of 10.50?tween 2018 and 2023. According to a different study by “Transparency Market Research,” the global market for OTF is expected to reach a valuation of approximately US$15.9 billion by 2024, with a “Compound Annual Growth Rate” of 9%, rising from 7.3 billion in 2015 to 15.9 billion USD by the end of 2024 . One of the top producers of OTF formulation, CURE Pharmaceuticals, has responded favorably to this TMR research. (42)
CONCLUSION:
In conclusion, buccal films have demonstrated exceptional potential as a versatile and efficacious drug delivery system. By leveraging the unique advantages of the buccal cavity, these films facilitate rapid absorption, enhanced bioavailability, and improved patient compliance. Despite initial challenges, advancements in mucoadhesive polymers, formulation design, and manufacturing processes have significantly enhanced their performance. The therapeutic applications of buccal films are diverse, encompassing pain management, oncology, cardiovascular diseases, and infectious diseases. Ongoing research focuses on optimizing drug permeability, exploring novel materials, and integrating nanotechnology. Standardization and regulatory guidance are crucial for commercial success. Interdisciplinary collaboration and investment in clinical trials will further establish the safety and efficacy of buccal films. As research continues to address existing challenges, buccal films are poised to revolutionize drug delivery. Their potential for personalized, efficient, and effective treatment options positions them as a transformative innovation in pharmaceutical technology. Ultimately, the future of buccal films holds immense promise for improving patient outcomes and quality of life. By harnessing the full potential of this delivery system, researchers and clinicians can create novel therapies that address unmet medical needs.
REFERENCES
Rutuja Jadhav*, Aadinath Sangle , Dr. Megha Salve, Buccal Films: Revolutionizing Oral Drug Delivery through Enhanced Bioavailability and Patient Compliance, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 11, 1097-1111. https://doi.org/10.5281/zenodo.14210586
10.5281/zenodo.14210586
