Technical Review Article | Open Access | Published 29th September 2026
Orodispersible Film-Based Pediatric Antiemetic Delivery Systems: Formulation Strategies, Evaluation and Future Perspectives
Authors: Mahendra Chouhan¹, Ragni Bathre¹, Seema Sharma², Sampat Singh Tanwar² , Devendra Singh Lodhi³,
Chameli Devi Institute of Pharmacy
Department of Pharmacy, Shri Vaishnav Vidyapeeth Vishwavidyalaya
Department of Pharmacy, Gyan Ganga Institute of Technology & Sciences
EJPPS | 313 (2026)| https://doi.org/10.37521/ejpps31312
Abstract
Pediatric emesis is a common and clinically significant problem associated with acute gastroenteritis, postoperative nausea, motion sickness, systemic infections, and drug-induced adverse effects. In children, recurrent vomiting may rapidly lead to dehydration, electrolyte imbalance, poor oral intake, reduced therapeutic compliance, and increased risk of hospitalization. These challenges highlight the need for age-appropriate, patient-centric antiemetic delivery systems that are effective, acceptable, and easy to administer. Conventional dosage forms, including syrups, tablets, and capsules, often fail to meet these requirements because of poor palatability, swallowing difficulties, dose inaccuracy, and administration challenges during active vomiting. Orodispersible films (ODFs) have emerged as a promising alternative owing to their rapid disintegration in the oral cavity, water-independent administration, ease of handling, portability, and potential for improved pediatric acceptability. Their formulation can be tailored through selection of suitable polymers, plasticizers, sweeteners, saliva stimulants, and taste-masking approaches to optimize drug release and patient compliance. This review highlights the clinical burden of pediatric emesis, examines the limitations of conventional antiemetic therapy, and discusses the growing rationale for ODF-based pediatric delivery systems. Particular attention is given to the need for age-appropriate formulations in children and the therapeutic advantages of film-based systems in improving medication adherence and ease of administration. Overall, ODFs represent a promising platform at the interface of pediatric clinical need and modern formulation science, with substantial potential to improve antiemetic therapy in children.
Keywords: Pediatric emesis; orodispersible films; pediatric drug delivery; antiemetic therapy; age-appropriate formulations; oral thin films
Graphical abstract
Introduction
Pediatric emesis is a frequent and clinically important symptom encountered in a broad range of acute and chronic conditions, including gastroenteritis, postoperative recovery, motion sickness, systemic infections, and drug-induced nausea. Although vomiting is often viewed as a self-limiting symptom, its clinical implications in children are far more serious than in adults because of their limited physiological reserves, greater dependency on caregivers, and increased vulnerability to dehydration and electrolyte imbalance. Recurrent vomiting can reduce oral intake, impair drug administration, aggravate nutritional compromise, and ultimately increase the likelihood of treatment failure and hospitalization ¹⁻³. In pediatric care, particularly in cases of acute gastroenteritis, effective control of vomiting is closely associated with the success of oral rehydration therapy, which remains the first-line management strategy for mild to moderate dehydration ¹,². Failure to control emesis may therefore transform a manageable condition into one requiring intravenous fluid therapy or inpatient care ³.
Despite the substantial burden of pediatric emesis, the development of suitable antiemetic formulations for children remains a major pharmaceutical challenge. Pediatric patients cannot be treated as simple miniature adults because dosage form performance is strongly influenced by age-related physiological and behavioural differences. Swallowing ability, taste sensitivity, oral cavity size, saliva volume, cognitive maturity, and dependence on caregivers all contribute to variability in formulation acceptability and therapeutic adherence ⁴⁻⁶. These considerations are particularly important in antiemetic therapy, where repeated administration, rapid onset of action, and high patient acceptability are essential for successful outcomes. Conventional dosage forms often do not align with these needs, thereby exposing a significant gap between therapeutic goals and formulation suitability.
Regulatory agencies have increasingly recognized this unmet need. Guidance from the International Council for Harmonisation (ICH) and the European Medicines Agency (EMA) emphasizes that age-appropriate dosage forms should be incorporated early in pediatric drug development and should ensure accurate dosing, safe administration, and practical usability across different pediatric age groups ⁴,⁵. Nevertheless, many pediatric therapies still depend on manipulated adult products, off-label administration, or formulations that are poorly accepted by children ⁶. Such practices may compromise dose precision, stability, safety, and adherence. Consequently, the search for child-friendly, flexible, and patient-centered dosage forms has become a major focus of current pediatric pharmaceutical research.
Among the emerging alternatives, orodispersible films (ODFs) have attracted considerable interest as a promising platform for pediatric drug delivery. ODFs are thin, rapidly disintegrating polymeric strips that are placed on the tongue or oral mucosa and usually dissolve without the need for water. This dosage form offers several advantages that are especially valuable in pediatric therapy, including ease of administration, reduced choking risk, portability, rapid disintegration, and the potential for accurate dosing ⁴,⁵. In children experiencing nausea or vomiting, these advantages become even more relevant, as conventional tablets, capsules, or even liquid formulations may be difficult to swallow or retain. By contrast, ODFs can simplify administration and improve the practicality of treatment in both home and clinical settings.
An additional factor driving interest in ODFs is the growing emphasis on medicine acceptability in pediatrics. Therapeutic effectiveness in children depends not only on pharmacodynamic efficacy but also on the ability to administer the medicine successfully and consistently. Palatability, mouthfeel, dosage form size, swallowability, and overall administration burden are important determinants of adherence ¹⁰⁻¹². Reviews on pediatric oral dosage forms have consistently shown that poor palatability and swallowing difficulty are major barriers to successful treatment, while evidence also indicates that substantial gaps remain in defining truly age-appropriate oral formulations across all pediatric subgroups ¹⁰⁻¹². In this context, ODFs are increasingly viewed as a formulation strategy that can combine pharmaceutical performance with improved real-world usability.
From a technological perspective, ODFs are highly versatile systems whose properties can be modulated through careful selection of film-forming polymers, plasticizers, sweeteners, saliva stimulants, solubilizers, and taste-masking agents. Manufacturing approaches such as solvent casting and hot-melt extrusion allow developers to optimize thickness, flexibility, mechanical strength, disintegration time, drug content uniformity, and dissolution behaviour ⁹,¹³,¹⁴. These features make ODFs attractive not only for pediatric antiemetic therapy but also for a broader range of pediatric indications requiring rapid and convenient oral administration. At the same time, the platform presents certain challenges, including limited drug loading capacity, moisture sensitivity, taste masking difficulties, and scale-up complexity ⁸,⁹,¹³. These limitations underscore the need for rational formulation design and comprehensive evaluation.
In view of these considerations, ODF-based pediatric antiemetic systems represent a compelling convergence of clinical necessity and formulation innovation. They have the potential to overcome many of the shortcomings of conventional oral dosage forms while supporting improved adherence, faster administration, and more patient-centered care in children. Accordingly, this review examines the clinical burden of pediatric emesis, discusses the limitations of currently available antiemetic formulations, and introduces the rationale for ODFs as a promising pediatric therapeutic platform. It further aims to establish the scientific and clinical foundation for subsequent discussion of formulation design, quality assessment, developmental challenges, and future opportunities in this evolving field.
Clinical Burden of Pediatric Emesis and Limitations of Conventional Therapy
Pediatric emesis is a common symptom across multiple clinical settings and remains an important cause of morbidity in infants and children. It may arise from gastrointestinal infections, postoperative recovery, motion sickness, systemic illness, neurological disorders, and adverse drug reactions. While vomiting in adults is often transient and manageable, in children it may produce disproportionately severe consequences because of smaller body size, higher fluid turnover, reduced physiological reserves, and limited capacity to communicate symptoms or self-manage treatment ¹⁵. As a result, repeated vomiting can quickly lead to dehydration, electrolyte disturbances, nutritional compromise, fatigue, irritability, and increased caregiver anxiety. These complications are particularly problematic in young children, in whom even short periods of poor oral intake may negatively affect general clinical status.
The burden of emesis is especially evident in acute gastroenteritis, one of the most common causes of pediatric vomiting worldwide. In such cases, vomiting directly interferes with oral rehydration, which is the preferred first-line treatment for mild to moderate dehydration ¹⁶. When oral fluids cannot be retained, the risk of treatment failure rises substantially, often necessitating intravenous hydration, emergency department visits, or hospitalization. Thus, pediatric emesis is not merely a distressing symptom but a clinically relevant factor that influences therapeutic success, healthcare utilization, and disease outcomes. Effective antiemetic management in children is therefore not only symptom-oriented but also functionally important in restoring fluid intake and maintaining treatment continuity.
Despite this clear need, conventional antiemetic dosage forms present several practical limitations in pediatric populations. Liquid preparations are often assumed to be the most suitable for children, yet their real-world use is associated with multiple drawbacks. Poor palatability, unpleasant aftertaste, need for measuring devices, and risk of dosing errors may all reduce treatment adherence. Moreover, in a child who is actively vomiting, the administration and retention of liquid medication can be difficult, leading to incomplete dosing or repeated administration attempts. Syrups and suspensions may also be inconvenient during travel, emergency care, or situations requiring rapid drug delivery.
Solid dosage forms such as tablets and capsules are even more problematic for many pediatric patients. Younger children frequently have difficulty swallowing these formulations, which can result in refusal, gagging, choking fear, or the need for crushing and manipulation ¹⁷. Such practices may alter drug release characteristics, reduce dose accuracy, and compromise product stability. In addition, many conventional formulations have not been specifically designed with pediatric sensory preferences or developmental needs in mind. An ideal pediatric antiemetic formulation should provide rapid onset of action, acceptable taste, flexible dosing, minimal choking risk, and ease of administration without reliance on water. Conventional dosage forms rarely fulfill all of these requirements simultaneously.
These limitations have stimulated increasing interest in patient-centric delivery systems better suited to pediatric use. Among these, ODFs are particularly attractive because they disintegrate rapidly in the oral cavity, reduce swallowing burden, and can be administered easily even in children experiencing nausea or active vomiting ¹⁸. Their development reflects a broader shift in pediatric pharmaceutical science away from simple adaptation of adult dosage forms and toward rational design of medicines that align with the practical, sensory, and clinical realities of childhood therapy.
Orodispersible Films as a Promising Platform for Pediatric Therapy
Orodispersible films (ODFs) have emerged as a highly promising platform for pediatric drug delivery, as they directly address several persistent limitations of conventional oral dosage forms. ODFs are thin, flexible polymeric strips designed to disintegrate rapidly in the oral cavity, generally without the need for water or chewing. This feature is especially advantageous in pediatric patients, including infants and young children, who often have difficulty swallowing tablets or capsules and may refuse or incompletely ingest liquid formulations due to poor palatability or administration burden ¹⁹. By combining rapid disintegration with ease of handling and administration, ODFs offer a patient-centric dosage form that aligns well with the practical realities of pediatric therapy.
One of the principal strengths of ODFs is their potential to improve treatment acceptability and adherence. In children, the success of any formulation depends not only on its pharmacological efficacy but also on whether it can be administered conveniently, safely, and repeatedly without resistance. Acceptability challenges such as spitting, crying, gagging, incomplete swallowing, and aversion to taste are well documented in pediatric medicine administration ²⁰. ODFs may reduce several of these barriers by offering a small, noninvasive, water-independent dosage form with minimal swallowing burden. Studies conducted in infants and preschool children have reported favourable caregiver perceptions and acceptable usability profiles for ODFs, supporting their relevance as age-appropriate formulations ²¹. A randomized clinical comparison in neonates and infants further showed that an orodispersible film was non-inferior to syrup in terms of acceptability, reinforcing the therapeutic promise of this dosage form in early pediatric age groups ²².
ODFs also provide important advantages from a formulation and therapeutic perspective. Because the film disintegrates rapidly on the tongue, it offers the possibility of fast drug release and convenient administration during conditions where swallowing conventional dosage forms may be difficult, such as nausea, vomiting, fever, pain, allergy, or acute distress. This feature is particularly relevant in pediatric antiemetic therapy, where vomiting itself may interfere with the retention of syrups, suspensions, tablets, or capsules. Moreover, the small unit size and thin structure of ODFs enhance portability and allow discreet administration in both home and healthcare settings ²³. These practical benefits make ODFs attractive not only for antiemetics but also for a wider range of pediatric indications requiring rapid and user-friendly drug delivery.
Another significant advantage of ODFs is their versatility in formulation. Their composition can be tailored by selecting appropriate film-forming polymers, plasticizers, sweeteners, saliva stimulants, solubilizers, and taste-masking systems. This enables formulation scientists to optimize key properties such as mechanical strength, flexibility, disintegration time, drug release, and palatability ⁹,¹³,¹⁷. Such flexibility is especially important in pediatric dosage form design, where taste and mouthfeel strongly influence compliance. ODFs may also support dose personalization more effectively than many conventional solid dosage forms, which is valuable in pediatric practice where doses frequently vary according to age or body weight ²⁴.
Despite these benefits, ODFs are not without limitations. Drug loading capacity is often restricted, and highly bitter or poorly soluble drugs may require advanced formulation strategies to achieve acceptable performance and palatability ²⁵. In addition, moisture sensitivity and mechanical fragility may complicate packaging and storage. Nevertheless, the overall balance of evidence indicates that ODFs represent one of the most promising age-appropriate oral delivery platforms currently available for pediatric therapy. Their ability to combine patient acceptability, administration convenience, and adaptable formulation design places them at the forefront of modern pediatric drug delivery research.
Formulation Design of Pediatric Orodispersible Films
The formulation design of pediatric ODFs requires a careful balance between rapid disintegration, sufficient mechanical integrity, dose precision, acceptable palatability, and excipient safety. Unlike adult oral films, pediatric ODFs must be specifically tailored to the developmental and physiological characteristics of children, including limited swallowing ability, increased taste sensitivity, smaller saliva volume, and greater vulnerability to excipient-related adverse effects ²⁶. Consequently, successful formulation design is not merely a matter of preparing a fast-dissolving film, but of engineering a dosage form that is safe, acceptable, robust, and clinically practical for pediatric use.
The most fundamental component of an ODF is the film-forming polymer, which determines matrix formation, flexibility, hydration, mechanical strength, and disintegration behaviour. Commonly used polymers include hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA), sodium alginate, gelatin, pullulan, and starch derivatives ³,¹³,¹⁷,¹⁹. The choice of polymer has a profound influence on the final film properties. Polymers such as HPMC and HPC are frequently preferred because they form smooth films with favourable mechanical performance and rapid hydration characteristics ²⁷. However, increasing polymer concentration may improve strength at the expense of longer disintegration time and increased film thickness, which can reduce pediatric acceptability.
Plasticizers are incorporated to improve film flexibility and reduce brittleness. Common plasticizers include glycerol, polyethylene glycol, and propylene glycol ⁹,¹⁷,¹⁹,²⁸. Their role is particularly important in pediatric ODFs because the films must remain sufficiently robust during handling, packaging, and administration while avoiding cracking or fragmentation. Plasticizer concentration must be optimized carefully, since insufficient amounts can lead to brittle films, whereas excessive levels may result in tackiness, prolonged drying, or reduced structural integrity.
A major determinant of pediatric ODF success is palatability. Because the film disintegrates directly in the oral cavity, any unpleasant taste is detected almost immediately. Thus, sweeteners, flavouring agents, and saliva stimulants are frequently added to improve overall sensory acceptance ²⁹. In cases where the active drug is bitter, more advanced taste-masking strategies may be required, including cyclodextrin complexation, ion-exchange resins, coated particles, or polymer-assisted masking systems ³⁰. Regulatory and scientific discussions on pediatric formulations repeatedly emphasize that taste masking and acceptability should be integrated early into formulation development rather than treated as secondary refinements ³¹.
Another key design challenge is drug loading and content uniformity. Due to their thin and lightweight structure, ODFs are generally better suited for low-dose or moderately potent drugs. High drug loads may compromise flexibility, thickness, homogeneity, and disintegration, thereby reducing both pharmaceutical quality and patient acceptability ³². This limitation often necessitates the use of solubilizers, dispersing systems, or multiparticulate incorporation strategies to maintain uniform drug distribution and acceptable film performance ³³. At the same time, all excipients used in pediatric ODFs must be selected with careful attention to age-specific safety, since some substances tolerated in adults may not be equally suitable for neonates, infants, or young children ³⁴.
The formulation design of pediatric ODFs is a multidimensional process centered on patient-oriented performance. The ideal pediatric film should disintegrate quickly in a small amount of saliva, mask unpleasant taste effectively, deliver a uniform dose, possess sufficient mechanical strength for handling, and use excipients with well-established pediatric safety profiles. These requirements explain both the promise and the complexity of ODFs as pediatric antiemetic delivery systems.
Table 1: Key formulation components in pediatric orodispersible films and their design roles
Formulation component | Common examples | Primary role in ODF design | Pediatric relevance |
Film-forming polymers | HPMC, HPC, PVA, sodium alginate, gelatin, pullulan, starch derivatives | Form the film matrix; determine strength, flexibility, hydration, and disintegration | Must support rapid disintegration with acceptable mechanical properties |
Plasticizers | Glycerol, PEG, propylene glycol | Improve flexibility, reduce brittleness, enhance folding endurance | Important for easy handling and prevention of cracking |
Sweeteners and flavors | Sucralose, xylitol, mannitol, fruit flavors | Improve taste and overall acceptability | Critical because palatability strongly affects adherence |
Saliva stimulants | Citric acid, malic acid | Promote wetting and faster disintegration | Helpful for rapid film breakdown in the oral cavity |
Solubilizers/surfactants | Cyclodextrins, polysorbates, cosolvent systems | Improve drug dispersion or solubility | Useful for poorly soluble or bitter drugs |
Taste-masking systems | Cyclodextrins, ion-exchange resins, coated particles | Reduce bitterness and improve sensory acceptance | Often essential for pediatric antiemetic drugs |
Stabilizers/preservatives | Formulation-specific | Maintain product stability and microbiological quality | Must be selected cautiously for pediatric safety |
Quality Assessment and Performance Evaluation
Quality assessment of pediatric orodispersible films (ODFs) is a critical stage in formulation development because the dosage form must simultaneously ensure rapid oral disintegration, adequate mechanical stability, dose precision, acceptable sensory attributes, and reproducible in vitro performance. Unlike conventional tablets or capsules, ODFs are thin, flexible systems whose quality depends strongly on formulation composition, casting method, drying conditions, residual moisture, and storage environment. Therefore, their evaluation requires a multidimensional framework encompassing physical, mechanical, chemical, performance-related, sensory, and stability parameters ³⁵.
The first level of assessment involves general appearance and dimensional uniformity. Films are visually examined for colour, transparency, smoothness, flexibility, absence of cracks, stickiness, and air bubbles. These properties influence not only product elegance but also patient acceptability and manufacturing consistency. Dimensional parameters such as film size, shape, thickness, and weight variation are then measured to ensure batch uniformity and dose reproducibility. Thickness is commonly determined at different points using a micrometer or digital caliper, while weight variation helps identify non-uniform casting or drying. In pediatric formulations, these attributes are particularly important because films must remain small, smooth, and easy to administer without discomfort ³⁶.
A second group of tests concerns surface characteristics and moisture-related behaviour. Surface pH is evaluated to ensure compatibility with the oral mucosa and to minimize the risk of irritation during administration. Moisture-related parameters, such as moisture content, moisture uptake, moisture loss, residual moisture, and hygroscopicity, are also important because water strongly affects film flexibility, brittleness, stickiness, microbial stability, and disintegration profile. Excessive moisture may lead to tackiness and reduced mechanical integrity, whereas insufficient moisture may make the film brittle and prone to cracking. For this reason, controlled-humidity studies and moisture-behaviour analysis are frequently incorporated into ODF evaluation protocols ³⁷.
The mechanical properties of ODFs are central to their practical performance. Since these films must withstand handling, packaging, cutting, transport, and administration, they need sufficient mechanical strength without becoming too rigid. Commonly assessed parameters include tensile strength, percent elongation, Young’s modulus, tear resistance, and folding endurance. Tensile strength measures the maximum stress a film can tolerate before breaking, while percent elongation reflects flexibility. Folding endurance indicates the number of times a film can be folded at the same location before breaking and is particularly relevant in predicting resistance to handling. A balanced mechanical profile is essential in pediatric therapy, where films are often removed from packaging and administered by caregivers rather than by the patients themselves ³⁸.
Another key domain of quality evaluation involves drug-related parameters. These include assay, drug content, content uniformity, and drug–excipient compatibility. Because ODFs are thin systems that often contain relatively low drug doses, even small variations in casting or drug dispersion can lead to clinically important inconsistencies in dose. Thus, content uniformity is one of the most critical quality attributes for pediatric ODFs. Compatibility studies using analytical techniques such as Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and related methods are also widely employed to confirm that the active drug remains stable within the film matrix and does not undergo undesirable interactions with excipients ³⁹.
The performance-related evaluation of ODFs primarily centers on disintegration and dissolution. In vitro disintegration time is a particularly important parameter because ODFs are designed for rapid breakup in the oral cavity. Different methods have been reported for this purpose, including Petri dish methods, slide-frame tests, texture analyzer-based approaches, and modified pharmacopoeial methods. Although no universal standard exists specifically for ODFs, rapid disintegration remains a defining feature of the platform. In vitro dissolution studies are then used to determine the rate and extent of drug release, often with special focus on early release behavior because pediatric ODFs are generally intended for immediate therapeutic action. Additional performance indicators such as wetting time, swelling index, and disintegration in simulated saliva are also useful in predicting oral behaviour ⁴⁰,⁴¹.
In pediatric ODF development, sensory and acceptability-related tests are equally important. These may include organoleptic assessment, taste evaluation, mouthfeel, grittiness, and palatability studies. Although these properties are more difficult to standardize than analytical or mechanical measurements, they are central to pediatric compliance because a technically sound formulation may still fail in practice if it is unpleasant to taste or irritating in the mouth. Finally, stability studies under accelerated and long-term storage conditions are necessary to confirm that the films maintain their appearance, drug content, disintegration profile, dissolution behaviour, and mechanical integrity over time. Taken together, these quality parameters define whether an ODF is not only pharmaceutically acceptable but also clinically and practically suitable for pediatric administration ⁴²,⁴³,⁴⁵.
Table 2: Major quality parameters commonly evaluated for pediatric orodispersible films
Category | Quality parameters |
Physical appearance | Colour, transparency, smoothness, flexibility, absence of cracks, stickiness, air bubbles |
Dimensional properties | Film size, shape, thickness, weight variation |
Surface properties | Surface pH, visual homogeneity |
Moisture-related properties | Moisture content, moisture uptake, moisture loss, residual moisture, hygroscopicity |
Mechanical properties | Tensile strength, percent elongation, Young’s modulus, tear resistance, folding endurance |
Drug-related properties | Drug content, assay, content uniformity, drug–excipient compatibility |
Performance tests | Wetting time, swelling index, in vitro disintegration time, disintegration in simulated saliva, in vitro dissolution/release profile |
Sensory evaluation | Taste, mouthfeel, grittiness, palatability, acceptability |
Stability evaluation | Accelerated stability, long-term stability, packaging compatibility, retention of release and mechanical properties |
Major Challenges in Development and Clinical Translation
Despite the substantial promise of pediatric ODFs, several barriers continue to hinder their translation from laboratory-scale research to routine clinical use. One of the foremost challenges is achieving true age-appropriateness across different pediatric subgroups. The pediatric population includes neonates, infants, children, and adolescents, each with distinct physiological, developmental, and behavioural characteristics. A formulation acceptable to one age group may be unsuitable for another because differences in swallowing ability, taste sensitivity, oral cavity size, saliva production, caregiver administration, and dose requirements significantly influence dosage form performance. Thus, developing a single ODF platform that is broadly acceptable across pediatric age ranges remains a demanding formulation objective ⁴⁴,⁴⁵.
A second major obstacle is drug loading and dose uniformity. ODFs are inherently thin and lightweight systems, which makes them highly convenient but also restricts the amount of active pharmaceutical ingredient that can be incorporated without compromising film thickness, flexibility, mouthfeel, or disintegration. This limitation is especially problematic for drugs requiring moderate to high doses. Increasing drug load may lead to brittle, thick, or nonuniform films, thereby affecting both pharmaceutical quality and patient acceptability. In pediatric therapy, where dosing often depends on age or body weight, maintaining precise dose uniformity is especially important because even minor dose deviations may influence therapeutic outcomes ⁴⁶,⁴⁷.
Another central challenge is taste masking and palatability. Since ODFs disintegrate directly in the oral cavity, the taste of the active ingredient is immediately exposed unless adequately masked. Many antiemetic drugs and related central-acting agents possess an unpleasant or bitter taste, making palatability a critical determinant of success. Poor taste is one of the most common reasons for treatment refusal in children, and this issue becomes particularly relevant when repeated dosing is required. Although sweeteners, flavouring agents, cyclodextrins, coated particles, and other masking techniques can improve sensory performance, robust taste masking remains one of the most persistent technological hurdles in pediatric ODF formulation ⁴⁸.
Moisture sensitivity and stability constitute another important challenge. ODFs are highly susceptible to environmental conditions, especially humidity and temperature. Excessive moisture may lead to tackiness, microbial growth, altered drug release, or reduced mechanical strength, whereas low moisture may cause brittleness and cracking. These factors complicate not only storage but also transportation and patient use, particularly in settings where environmental control is limited. As a result, films that perform well under laboratory conditions may behave differently during real-world handling, packaging, or shelf-life storage. This makes packaging design and stability optimization critical components of successful product development ⁴⁹.
The transition from bench-scale preparation to industrial manufacturing introduces further difficulties related to scale-up and process reproducibility. Uniform casting, controlled drying, accurate cutting, and consistent drug distribution are technically challenging when production is expanded from small batches to commercial scale. Small changes in drying temperature, solvent evaporation rate, viscosity, or casting thickness may result in significant variability in film properties. Although techniques such as hot-melt extrusion and 3D printing offer promising alternatives, these methods still require broader validation for routine pediatric ODF production. Consequently, many reported ODF systems remain proof-of-concept formulations rather than commercially viable pediatric products ⁵⁰.
Emerging Innovations and Advanced Film Technologies
Recent advances in pediatric orodispersible film (ODF) technology are shifting the platform from simple fast-disintegrating strips toward more sophisticated, patient-centric systems with improved functionality and translational relevance. One of the most notable innovations is the application of three-dimensional (3D) printing to fabricate personalized pediatric ODFs. This approach enables precise control over dose, film geometry, drug distribution, and material composition, which is particularly valuable in pediatric therapy where dosing often varies according to age, body weight, or clinical need. A recent 2025 study demonstrated direct powder extrusion 3D printing of midazolam/γ-cyclodextrin-loaded ODFs as personalized pediatric dosage forms, highlighting the feasibility of on-demand film production with improved dissolution behaviour and formulation flexibility ⁵¹. These developments suggest that 3D printing may become an important enabling technology for individualized pediatric medicines.
Another important trend is the development of hybrid and multifunctional ODF systems. Conventional ODFs are generally designed for rapid disintegration and immediate drug release; however, emerging film technologies now incorporate additional functions such as sustained release, multiparticulate loading, and modified oral residence behaviour. In 2025, Huang et al. reported a pediatric ODF loaded with dual-coated sustained-release microparticles using topiramate as a model drug, demonstrating that film-based platforms can be adapted beyond immediate-release delivery while retaining age-appropriate administration benefits ⁵². This is a significant advance because it broadens the therapeutic scope of pediatric ODFs and may make the platform applicable to drugs requiring prolonged exposure or more controlled pharmacokinetics.
Innovation is also occurring at the level of materials, excipients, and formulation architecture. Contemporary research is increasingly focused on multifunctional polymers, mucoadhesive components, advanced taste-masking systems, and biopolymer-based matrices that enhance flexibility, stability, mucosal compatibility, and patient acceptability. The broader direction of the field suggests a transition from passive disintegrating films toward engineered delivery systems capable of combining rapid oral administration with targeted mechanical, sensory, and release characteristics. In pediatric use, such advances are particularly relevant because they can help address persistent challenges related to palatability, dose individualization, and formulation robustness ⁵³.
Regulatory Landscape and Future Opportunities
The regulatory landscape for pediatric ODFs is shaped primarily by broader frameworks governing pediatric medicine development, rather than by film-specific guidelines alone. The ICH E11(R1) guideline emphasizes that pediatric drug development should facilitate timely availability of medicines for children and recognizes the importance of age-appropriate dosage forms that support accurate dosing, safe administration, and better patient compliance ⁵⁴,⁵⁵. These principles are directly relevant to ODFs because their major therapeutic value lies in improving swallowability, acceptability, and ease of administration in pediatric populations.
In parallel, recent regulatory developments such as ICH E11A on pediatric extrapolation reinforce a more systematic and efficient pediatric development strategy. The E11A guideline, finalized in 2024 and adopted into FDA guidance in early 2025, provides an internationally harmonized framework for leveraging extrapolation in pediatric drug development and authorization ⁵⁶. Although E11A is not specific to ODFs, it reflects an important regulatory shift toward evidence-based, streamlined pediatric development pathways. For ODF-based products, this creates a favourable context in which age-appropriate formulations supported by robust pharmaceutical quality, usability data, and clinical rationale may be more efficiently advanced through development ⁵⁷.
From a translational perspective, the future opportunities for pediatric ODFs are substantial. The strongest prospects lie in personalized dosing, digitally enabled manufacturing, improved taste-masking technologies, and broader application in conditions requiring rapid, water-independent administration. Regulatory science is also moving toward more patient-centered development models, which may favour dosage forms such as ODFs that align with practical administration needs and adherence goals in children ⁵⁸. However, successful regulatory progression will still require clear demonstration of pharmaceutical quality, content uniformity, stability, excipient safety, packaging suitability, and acceptability across relevant pediatric age groups. Thus, the future growth of pediatric ODFs will depend not only on innovation in film technology but also on closer alignment between formulation design, regulatory expectations, and real-world pediatric usability.
Conclusion and Outlook
Orodispersible films represent a highly promising platform for pediatric antiemetic therapy because they address several of the most important shortcomings of conventional formulations, including poor swallowability, administration difficulties during active vomiting, and reduced treatment acceptability. Their rapid disintegration in the oral cavity, water-independent administration, portability, and potential for accurate dosing make them particularly attractive for pediatric use, where therapeutic success depends as much on ease of administration and adherence as on pharmacological efficacy.
At the same time, the successful development of pediatric ODFs requires more than simple fast disintegration. Rational formulation design must carefully integrate polymer selection, mechanical performance, palatability, dose precision, moisture stability, and pediatric excipient safety. These factors are especially important in children, whose age-related physiological and behavioural variability can strongly influence dosage form performance in real-world settings. Accordingly, pediatric ODFs should be regarded not merely as modified oral films, but as highly specialized, patient-oriented systems that demand coordinated consideration of pharmaceutical science, pediatric medicine, and regulatory acceptability.
The outlook for this field remains highly encouraging. Emerging technologies such as 3D printing, multifunctional film architectures, advanced taste-masking systems, and digitally controlled manufacturing workflows are expanding the capabilities of ODFs beyond conventional immediate-release products. These innovations may enable individualized pediatric dosing, improved sensory acceptance, and wider applicability to drugs that were previously considered unsuitable for film-based delivery. Nevertheless, broader clinical translation will require stronger scale-up strategies, standardized performance evaluation, well-designed pediatric acceptability studies, and continued regulatory engagement. Overall, ODF-based pediatric antiemetic delivery systems represent a compelling intersection of clinical need and pharmaceutical innovation, with strong potential to become an important component of future pediatric drug delivery practice.
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Authors
Mahendra Chouhan¹, Ragni Bathre¹, Seema Sharma², Sampat Singh Tanwar² , Devendra Singh Lodhi³*
Corresponding Author: Sampat Singh Tanwar
Assistant Professor, Department of Pharmacy, Shri Vaishnav Vidyapeeth Vishwavidyalaya, Indore, M.P, India
Email: sampattanwar1999@gmail.com,
Orcid id: 0009-0001-3368-8636
Mahendra Chouhan¹a, Ragni Bathre¹b, Seema Sharma², Sampat Singh Tanwar² , Devendra Singh Lodhi³*
1a. Associate Professor, Department of Pharmaceutics, Chameli Devi Institute of Pharmacy, Umrikheda, Indore, Madhya Pradesh, India, mahendra7666@gmail.com
1b. Department of Pharmaceutics, Chameli Devi Institute of Pharmacy, Umrikheda, Indore, Madhya Pradesh, India
2. Assistant Professor, Department of Pharmacy, Shri Vaishnav Vidyapeeth Vishwavidyalaya, Indore, M.P, India, seemasharmapharm@gmail.com, Orcid id: 0009-0003-9641-4127
3. Professor, Department of Pharmacy, Gyan Ganga Institute of Technology & Sciences, Jabalpur, M.P, India, devendralodhi86@gmail.com
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