Oral Thin Film Research Articles

Biocompatible Natural Polymers and Cutting-Edge Fabrication Techniques in the Development of Next-Generation Oral Thin Films for Enhanced Drug Delivery Systems.

Oral thin films are changing the way drugs are delivered, making drug administration more convenient and patient-friendly. This review delves into the fascinating possibilities of natural polymers in thin film design. We consider the benefits of biocompatible polymers produced from chitosan, gelatin, and pullulan. Their intrinsic biodegradability and safety make them excellent for use with a wide range of patients. Additionally, the research investigates novel strategies for creating these distinctive drug delivery systems. We look beyond standard solvent casting techniques, hot melt extrusion methods, rolling methods, etc. These technologies provide exact control over film qualities, allowing for tailored medication delivery and increased patient compliance. This review seeks to bridge the gap between natural polymers and cutting-edge fabrication processes. By investigating this combination, we pave the road for the development of next-generation oral thin films that are more efficacious, patient-acceptable, and environmentally-friendly.

Exploring the Advancements and Applications of Oral Thin Film Technology

This comprehensive review delves into the recent advancements and diverse applications of oral thin film (OTF) technology in the field of pharmaceuticals. The aim is to provide a thorough exploration of the evolution of OTFs, their unique characteristics, and their expanding role in drug delivery systems. A systematic analysis of the literature was conducted to gather information on the formulation techniques, properties, and challenges associated with OTFs. Additionally, recent developments, innovations, and future trends in OTF technology were examined to understand the dynamic landscape of this drug delivery system. The review highlights the key properties of OTFs, including rapid disintegration, enhanced bioavailability, and patient-centric advantages. Various manufacturing techniques, such as solvent casting, hot melt extrusion, and 3D printing, were explored for their impact on OTF formulation. Challenges, including stability issues and taste masking complexities, were identified. Recent innovations, such as nanotechnology integration, personalized medicine applications, and the use of digital health platforms, showcase the ongoing efforts to overcome these challenges. Oral thin film technology stands at the forefront of pharmaceutical innovation, offering a patient-friendly and adaptable drug delivery system. As evidenced by recent developments, the integration of advanced technologies, personalized medicine approaches, and sustainable practices positions OTFs as a transformative force in the future of drug delivery. The exploration of these advancements and applications contributes to a deeper understanding of the potential impact of OTF technology on healthcare.

Development of a new method for analyzing the behavior of rapidly dissolving films in contact with liquids

Oral Thin Film (OTF) is a promising dosage form, easy to use and patient-friendly drug delivery systems suitable for every consumer profile. This dosage form ensures safety, stability, and acceptability of the drug, that's why it can be a good alternative for tablets and capsules for children and elderly therapies. As no detailed monography of OTFs including characterization methods and uniform requirements has been presented in any of the pharmacopoeias to date, this study focuses on the development of an innovative analyzing method to characterize the OTF behavior and particularly to determine its disintegration time by goniometry. These parameters are key for the development of OTFs and for studying, at an early stage, the impact of formulation and process variables on product quality and impacting Critical Quality Attributes (CQA) by a Quality by Design approach.Different model OTF preparations were investigated as models to determine the suitability of the disintegration test systems. These placebos OTF were used to compare the disintegration times obtained by the tablets pharmacopeial method (conducted in 800 mL of distilled water) and the novel proposed method. As expected, the disintegration times determined by the proposed method were similar than those obtained by the conventional disintegration test. Moreover, they seem more reliable to the in vivo behavior because of the small amount of solvent used. The experiments showed acceptable reproducibility (low variation within sample replicates due to a well-defined determination of the measurement endpoint). This method provides clear endpoint detection and is applicable for different types of OTFs based on different polymers. Moreover, a better understanding of the physical-chemical properties of oral thin films towards water could be obtained. This new method of analysis could provide a valuable approach to the development of new OTF formulas, thanks to the different information that can be obtained, such as critical energy, free energy and polar and dispersive components.

Formulation and evaluation of melatonin as fast dissolving oral strips using combined polymers

Background and objective: Fast-dissolving oral thin film (FDOF) is a novel and most advanced form of solid dosage form that dissolves or disintegrates in 1 minute when put in the mouth without water or chewing. Pre-gastric absorption of FODFs from the mouth, pharynx, and esophagus as saliva flows down into the stomach would improve the therapeutic benefit of the drug as oral films disintegrated in the mouth. The study is designed and purposed to use most water soluble, best type and concentration of polymers to be selected for use in combination to formulate melatonin oral thin films. Different types of synthetic water soluble polymers were utilized the preparation of films (hydroxypropyl methyl cellulose HPMC15M, sodium carboxy methyl cellulose NACMC). Methods: Solvent casting method was performed for preparation of twelve placebo films at the beginning, to obtain and select suitable polymer type and concentration for use in combination to be formulated for drug loading. The films were evaluated for their characteristics like mechanical properties (thickness and folding endurance), surface pH and disintegration time. Percentage of release and assay of melatonin was taken. Comparison studies were performed on melatonin films from this study with melatonin oral disintegrating tablets release profiles. Best batch could be selected. Drug-excipient compatibility carried out as pre formulation study to see whether there is interaction between the drug and excipients used. Results: Results from FT-IR showed no interaction between melatonin and polymers used, the prepared formulations were clear, transparent, non-sticky and easily removed from the plate surface with the thickness ranging from (0.04-0.07) mm depending on the polymer concentration. The times required for the films to disintegrate was ranging from 21-26 seconds, and the majority of melatonin was released within first 2 minutes within the dosage form. Conclusion: Melatonin can be formulated as fast dissolving oral films using combination of water-soluble polymers by solvent casting method to obtain ease of administration without using water during administration, fast onset of action resulted from rapid disintegration.

Formulation and evaluation of dosage form of fast dissolving oral film of Rofecoxib

Rofecoxib is utilized for the treatment of osteoarthritis, rheumatoid joint inflammation, intense torment in grown-ups, and essential dysmenorrhea, just as intense therapy of headache assaults with or without emanations. Rofecoxib is strong. This compound has a place with the stilbenes. These are natural mixes containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are acquired from the normal phenylpropene (C6-C3) skeleton building block. The presentation of at least one hydroxyl gathering to a phenyl ring leads to stilbenoids. Rofecoxib has a half-existence of 17 hours and its mean oral bioavailability at restoratively suggested dosages of 125,25,and 50 mg is roughly 93%. The proteins that rofecoxib target incorporate elastin and prostaglandin G/H synthase Cytochrome P4501A2, Cytochrome P4503A4, Cytochrome P4502C9, Cytochrome P4502C8, and Prostaglandin G/H synthase1 are known to processor of Rofecoxib. Rofecoxib oral thin films were prepared from the evaluation studies RCX2 with 98.14% drug release is considered as the optimized formulation.

Optimization of Oral Thin Film Cetirizine HCI by Response Surface Methodology: Disintegration and Mechanical Properties

Optimization of Oral Thin Film Cetirizine HCI by Response Surface Methodology: Disintegration and Mechanical Properties

Esketamine combined with a mindfulness-based intervention for individuals with alcohol problems.

Alcohol use disorder (AUD) is a major public health issue, posing harmful consequences for individuals and society. Recent advances in addiction research have highlighted the therapeutic potential of ketamine-assisted therapy for AUD. However, the exact mechanisms underlying its effectiveness remain unknown. This double-blind, pilot study aimed to investigate esketamine combined with mindfulness-based intervention (MBI) to examine whether esketamine enhances engagement in MBI for individuals with alcohol misuse problems and whether enhanced engagement has any impact on alcohol-related outcomes. In all, 28 individuals with alcohol problems were randomly assigned to receive sublingual esketamine hydrochloride (AWKN002: 115.1 mg) or vitamin C (placebo) in an oral thin film and took part in 2 weeks of daily MBI. Participants were assessed on various self-report measures, including mindfulness, engagement in MBI (physical and psychological), alcohol cravings and consumption. Esketamine enhanced psychological engagement with a daily MBI, compared to placebo, and led to transient decreases in alcohol cravings. Esketamine also resulted in significantly greater mystical experiences and dissociative states compared to placebo. The findings suggest that esketamine may improve treatment outcomes when combined with mindfulness-based therapies through its ability to increase engagement with meditative practice.

Quality by Design (QbD) Aided Formulation Optimization of Amlodipine Besylate Oral Thin Film

Quality by Design (QbD) Aided Formulation Optimization of Amlodipine Besylate Oral Thin Film

UTILIZATION RED DRAGON FRUIT PEEL (HYLOCEREUS POLYRHIZUS) ETHANOL EXTRACT IN ORAL THIN FILM STRIP AS A MOUTH FRESHENER

Objective: The aim of this study was to formulate an oral thin film strip (OTFS) contained the red dragon fruit peel (RDFP) ethanol extract (Hylocereus polyrhizus) and evaluate the characteristic, stability and antibacterial activity against Streptococcus mutans (S. mutans). Methods: The film was made using the solvent casting method by adding a variety of concentration ethanol extract of red dragon fruit peel (5%, 10%, and 15%). The films were evaluated in organoleptic test, weight, thickness, pH, disintegration time, folding endurance, stability test and antibacterial activity. Results: The results showed that the film provided a distinctive color, aroma, and taste of the extract. The result of film evaluation had weight between 0.07-0.21 g, thickness between 0.10-0.20 mm, pH between 5.70-5.99, disintegration time between 34.99-49.13 s, and folding endurance between 321.00-812.83 times. The films were stable for 2 mo at a variety storage temperature (4±2 ℃, 28±2 ℃, and 40±2 ℃). The films showed antibacterial activity for 5%, 10% and 15% with the diameter of inhibition 8.5 mm, 10.8 mm, and 12.9 mm, respectively. Conclusion: Ethanol extract of RDFP can be utilized as a mouth freshener film that is stable for 2 mo and has antibacterial activity against S. mutans.

AN OVERVIEW ON ORAL THIN FILMS–METHODOLOGY, CHARACTERIZATION AND CURRENT APPROACH

The pharmaceutical sector is looking for new ways to deliver drugs, and one such way is through thin films. It has been said that thin films offer an alternative to traditional dosage forms. They offer rapid, local, or systemic effects and are a very flexible platform. Furthermore, patients with dysphagia, elderly, paediatrics, or bedridden patients, as well as those who have difficulty accessing water, can easily utilize these systems on their own. There are several ways to administer these drug delivery systems, including transdermally, ocularly, buccally, sublingually, and orally. One of the most creative and patient-focused novel drug delivery systems is Orodispersible Thin Films (OTF). Numerous pharmaceutical companies and academic experts worldwide are currently investigating the potential of these films for delivering drugs derived from both synthetic and natural sources. The beauty of this special drug delivery method is that, as we can see from the subjects' consumption of conventional dosage forms (tablets, capsules), they don't require water to be consumed. Furthermore, these delivery methods do a great job of encouraging patient compliance in general, especially in the case of both older and pediatric patients. This review shows a detailed review of oral thin film its applications and method of preparation; mainly focus of this research is thin film introduction to researchers and last 10 y of research on thin film with drugs and polymers used in research.

A REVIEW ON MOUTH DISSOLVING FILM

Oral route is considered as one of the most convenient route for administration of various pharmaceutical dosage forms like, tablet, capsule, syrup, suspension and emulsion. Fast Dissolving Drug Delivery systems have developed various fast disintegrating preparations like mouth dissolving film, MDT. Oral thin film are new dosage form that are prepared from hydrophilic polymer which are when placed in mouth, buccal cavity disintegrate rapidly. Mouth dissolving film is superior as compare to mouth dissolving tablet as the cost of production is low. Geriatric and pediatric patients are facing difficulty in swallowing of tablet and capsule, the oral film can bypass it, along with that it has other advantages like self-administrable, fast dissolving, rapid absorption that make it versatile dosage form. The aim of present study is to enlighten specifically different polymer along with their concentrations and applications. This study also focuses on use of plasticizer, polymer, sweetener, different methods which are used for the preparation of oral films and various evaluation parameter of the film.

NOVEL BIOMATERIAL ASSISTED DRUG DELIVERY SYSTEMS FOR THE MANAGEMENT OF ORAL DISEASES–FUTURE THERAPEUTIC APPROACHES

Oral health is integral to maintaining systemic health as the mouth and oral cavity connect our digestive system with the external environment. The incidence of oro-dental disorders has been emerging as a serious threat to the healthcare sector owing to the increasing complexity of oral microbiome. Conventional treatment modalities are often limited by drug resistance and unwanted inflammatory responses. Recently, therapeutic strategies that can reinstate microbial homeostasis in the oral microenvironment have been implicated in the management of odontogenic infections. Biomaterial-based drug delivery systems, including nanocarriers, dendrimers, hydrogels, oral thin films, oral patches, and other stimuli-responsive polymeric systems, facilitate targeted administration of antimicrobials and anti-inflammatory agents to the site of infection. Bio adhesivity of the polymeric carriers facilitates faster disintegration and accurate dosing of the pharmacological agent to the target site. Moreover, restorative dentistry has been revolutionized by the advent of bio-functional templates that offer improved osseointegration and long-term stability of implants. A comprehensive review of the potential applications of biomaterial-mediated therapeutic strategies in the management of caries, peri-implantitis, periodontitis, and other oro-dental infections is explored here.

Design and Characterization of Fast-Dissolving Oral Film of Apixaban.

Following the COVID-19 pandemic, microvascular and macrovascular thrombotic problems emerged that required anticoagulants. Apixaban (RN) is a factor Xa inhibitor that treats deep vein thrombosis and the two forms of artery diseases (coronary artery disease and peripheral artery disease). The study objective was to create fast-disintegrating Apixaban Oral Thin Films (OTF) with the help of various super disintegrants to shorten disintegration time and enhance drug release in order to assist patients who have difficulty in swallowing conventional dosage forms and increase bioavailability. OTF was created using the solvent casting method. A 22 factorial design was employed in Design-Expert® software to develop an ideal formula. The optimized film formula pH, drug content, disintegration time, folding endurance, and dissolution rate were estimated, and the film was subjected to a short-term stability study. The optimized formula exhibited a cumulative drug release of 93.47% in 60 sec. The drug's in vitro release pattern shows first-order kinetics and fickian diffusion was the mechanism of drug release. These findings supported that Apixaban OTFs offer a quick release of the medication from the administration site into the systemic circulation.

Preparation and evaluation of Oral Thin Film of Eugenol for tooth decay

Preparation and evaluation of Oral Thin Film of Eugenol for tooth decay

Incorporation of Loratadine-Cyclodextrin Complexes in Oral Thin Films for Rapid Drug Delivery

Rapidly dissolving polymer thin films, or oral thin films (OTFs), have recently emerged as an improved oral drug delivery vehicle with its ability to bypass liver first pass metabolism, longer shelf-life, and simpler transport and distribution requirements, compared to traditional tablets and liquid formulations. Loratadine (LOR), an antihistamine commonly used to treat allergic rhinitis, undergoes liver first pass metabolism and is a prime candidate for incorporation within an OTF. However, loratadine is a BCS II drug with low aqueous solubility. Herein, the solubility of loratadine was improved by complexation with methyl β-cyclodextrin (MBCD) by co-evaporation of 2:1, 1:1, and 1:2 LOR:MBCD ratios and incorporation into a pullulan-based OTF at 4 wt% by solvent casting at 50 °C for 30 – 35 min. A therapeutically relevant 10 mg LOR dose could be prepared in a 3 cm by 3 cm OTF. The feasibility of complexation was observed with a Bs-type phase solubility diagram, and complexation itself was confirmed via differential scanning calorimetry (DSC) by disappearance of the LOR melting peak, Fourier-transform infrared spectroscopy (FTIR) by shifting of the C=O peak, via 1H NMR spectroscopy by downfield shifting and change in peak multiplicity of the LOR aromatic protons, and via diffusion-ordered spectroscopy by a decrease in the diffusion coefficient of LOR:MBCD complex. LOR:MBCD could be incorporated homogeneously throughout an OTF, and LOR:MBCD OTFs exhibited reasonable mechanical strength and endured 12 ± 3 folds before breaking. LOR:MBCD OTFs disintegrated within 38 ± 10 s. The cumulative in vitro release of LOR:MBCD OTFs peaked at 80 % within 3–4 min of dissolution, and LOR in LOR:MBCD OTFs exhibited permeability across a 0.22 μm nitrocellulose membrane, demonstrating its applicability as a rapid drug delivery vehicle.

Development of a tadalafil transdermal formulation and evaluation of its ability to in vitro transdermal permeate using Strat-M® membrane

Tadalafil (TDF) has low water solubility, high intestinal permeability and belongs to the Biopharmaceutics Classification System (BCS) Class II. Due to high intestinal permeability, only oral administration (tablets) and oral thin film formulations have been developed. Therefore, it is necessary to develop various formulations, such as external formulations and transdermal absorption formulations requested by patients. The purpose of this study is to improve the solubility and skin permeability of TDF, and to develop a novel transdermal formulation with secured stability over time. The research strategy is to determine solvents that will improve TDF solubility and to screen substances that will enhance TDF permeability. Skin penetration tests were simulated by using a Strat-M® membrane in Franz diffusion cell systems. The optimal formulation (F1, consisting of TDF/HDTMA-Br at a ratio of 1:10 [weight/weight] in DPG) observed the highest permeability compared to all formulations in PBS (pH 7.4). Changes in thermal property of F1 formulation was observed and maintained its stability over 12 months including drug content (μg/mL), appearance, pH, and permeation (μg/cm2). In conclusion, DPG played a supported role in improving both TDF solubilization and permeability, whereas HDTMA-Br played a key role in enhancing permeability. It is thought that these results will be supplemented in the future to conduct research and experiments on humans.

An Overview of Oral Thin Film Drug Delivery Systems with Fast Dissolving Films

Fast-dissolving oral thin films (OTFs), rather than tablets, are the product of choice for many pharmaceutical businesses. The benefits of tablets (precise dose, simple administration) and liquid dosage forms (easily swallowed, quick bioavailability) are all present in films. Four out of five patients, according to statistics, prefer orally disintegrating dose forms over traditional solid oral dosage forms. Children, the elderly, people who are bedridden, people who are emetic, and those who have CNS illnesses have trouble swallowing or digesting solid dose forms. Many of these individuals refuse to take solid dose forms because they are afraid of choking. OTFs are immediately moistened by saliva when put on the tongue's tip or base. Because of this, OTFs quickly hydrate before dissolving or disintegrating to release the drug for local or systemic absorption. This technology offers a solid foundation for the creation of patent-compliant items and for extending the patent protection of currently available goods. Fast-dissolving oral thin films can be used for a variety of purposes, including gastroprotective and sublingual delivery systems in addition to buccal fast-dissolving systems. This study emphasizes the composition, detailing the numerous natural and synthetic polymer kinds, diverse manufacturing processes, packaging materials, and assessment tests for OTFs.

A review on orodispersible drug delivery system

The future of drug delivery holds great promise for orally dispersible dose formulations, which make application simple since no water requirement as compared to conventional solid dosage forms which requires significant volumes of fluids for administration. The objective for development of ODF provides a substitute for pills, syrups, and tablets in treating vomiting as well as nausea, particularly in children. On the basis of transdermal patch delivery system, a novel oral films drug delivery has been introduced. Fast dissolving films disintegrates quickly when come in contact with salivary secretion in the oral mucosa and released the drug fast approximately within 3 mins. ODFs are of different types, like sustained or controlled release, oral patches and fast dissolving films. They can be manufactured using a variety of method including solvent and semi solid casting, hot melt and solid dispersion extrusion, spray drying and rolling. Among them solvent casting method is the most employed method. ODFs comprises of active ingredient, polymer, plasticizer and additives like surfactants, sweetening and coloring agents. ODFs preparation requires hydrophilic polymer which provides quick dissolution in the oral cavity. Hydrophilic polymer act as base for ODFs formulation as they impart mouth feel and mechanical properties of the ODFs also dependent of polymer type. Oral thin-film provide fast drug dissolution precise dosage in a portable, safe, and handy manner that doesn't required water or any special equipment. This review article comprises of different methods for ODFs preparations, ODFs ingredients, ODFs benefits and drawbacks and their packaging.

A review on orodispersible drug delivery system

The future of drug delivery holds great promise for orally dispersible dose formulations, which make application simple since no water requirement as compared to conventional solid dosage forms which requires significant volumes of fluids for administration. The objective for development of ODF provides a substitute for pills, syrups, and tablets in treating vomiting as well as nausea, particularly in children. On the basis of transdermal patch delivery system, a novel oral films drug delivery has been introduced. Fast dissolving films disintegrates quickly when come in contact with salivary secretion in the oral mucosa and released the drug fast approximately within 3 mins. ODFs are of different types, like sustained or controlled release, oral patches and fast dissolving films. They can be manufactured using a variety of method including solvent and semi solid casting, hot melt and solid dispersion extrusion, spray drying and rolling. Among them solvent casting method is the most employed method. ODFs comprises of active ingredient, polymer, plasticizer and additives like surfactants, sweetening and coloring agents. ODFs preparation requires hydrophilic polymer which provides quick dissolution in the oral cavity. Hydrophilic polymer act as base for ODFs formulation as they impart mouth feel and mechanical properties of the ODFs also dependent of polymer type. Oral thin-film provide fast drug dissolution precise dosage in a portable, safe, and handy manner that doesn't required water or any special equipment. This review article comprises of different methods for ODFs preparations, ODFs ingredients, ODFs benefits and drawbacks and their packaging.

Optimized vitamin D repletion with oral thin film cholecalciferol in patients undergoing stem cell transplant

AbstractVitamin D deficiency is common in childhood, pervasive before and after bone marrow transplant, and is associated with increased incidence of graft-versus-host disease (GVHD) and decreased survival in patients undergoing hematopoietic stem cell transplant (HSCT). Numerous barriers impede replacement, including malabsorption secondary to gut GVHD, mucositis, inability to take capsules, kidney disease, liver disease, and infection; many patients remain refractory despite vitamin D therapy. We hypothesized that a different formulation of cholecalciferol, administered on the tongue as a readily dissolving oral thin film (OTF), would ease administration and facilitate therapeutic vitamin D levels (>35 ng/mL) in patients who are refractory. In this prospective pilot study, we evaluated 20 patients after HSCT (range, day +21 - day +428 at enrollment) with serum vitamin D levels ≤35 ng/mL. Cholecalciferol OTF strips were administered for 12 weeks. Dosing was based on patient body weight and titrated per individual pharmacokinetics. Wilcoxon matched-pairs signed-rank test demonstrated marked improvement in all 20 patients who were formerly refractory, increasing from a median baseline vitamin D level of 29.2 ng/mL to 58 ng/mL at end of study (P < .0001). All patients demonstrated improvement in serum vitamin D level by week 4 on study, some of whom had been refractory for years prior. Median dose was 1 OTF strip (40 000 IU) per week. No toxicity was observed. This formulation proved to be safe, effective, efficient, and well received. We are eager to explore other patient populations, which might benefit from this promising development, and other therapeutics that might be optimized using this mode of delivery. This trial was registered at www.clinicaltrials.gov as #NCT04818957.