Orally Disintegrating Film Research Articles

Chitosan/pre-gelatinized waxy corn starch composite edible orally disintegrating film for taurine delivery

In this study, chitosan/per-gelatinized waxy corn starch composite edible orally disintegrating films (ODFs) incorporated with taurine were prepared and the morphology, release behavior and storage stability of the ODFs were investigated. The XRD, ATR-FTIR and microscopic investigation results revealed that taurine could be uniformly dispersed in the film matrix. The optimal level of taurine addition was 1.0% (w/w). The incorporation of taurine improved the apparent morphology, mechanical properties and water holding capacity while slightly increased the film thickness, disintegration time and contact angle of the composite films. In addition, taurine exhibited a rapid release behavior in the films. The fitted results of the Ritger-Peppas model indicated that the release mechanism of taurine in the composite films was mainly Fickian diffusion with minor skeleton erosion. As a delivery carrier, the composite film had a positive effect on the preservation of taurine, increasing the retention of taurine by 8.34% ± 1.48% during storage. The study confirmed the feasibility for the development of taurine ODF carriers and provided a basis for the development of functional packaging materials.

PVA-based formulations as a design-technology platform for orally disintegrating film matrices

In the majority of pharmaceutical applications, polymers are employed extensively in a diverse range of pharmaceutical products, serving as indispensable components of contemporary solid oral dosage forms. A comprehensive understanding of the properties of polymers and selection the appropriate methods of characterization is essential for the design and development of novel drug delivery systems and manufacturing processes. Orally disintegrating film (ODF) formulations are considered to be a potential substitute to traditional oral dosage forms and an alternative method of drug administration for children and uncooperative adult patients, including those with swallowing difficulties. A multitude of pharmaceutical formulations with varying mechanical and biopharmaceutical properties have emerged from the modification of the original polymeric bulk. Here we propose different formulation approaches, i.e. solvent casting (SC), 3D printing (3DP), electrospinning (ES), and lyophilization (LP) that enabled us to adjust the disintegration time and the release profile of poorly water soluble haloperidol (HAL, BCS class II) from PVA (polyvinyl alcohol) based polymer films while maintaining similar hydrogel composition. In this study, the solubility of haloperidol in aqueous solution was improved by the addition of lactic acid. The prepared films were evaluated for their morphology (SEM, micro-CT), physicochemical and biopharmaceutical properties. TMDSC, TGA and PXRD were employed for extensive thermal and structural analysis of fabricated materials and their stability. These results allowed us to establish correlations between preparation technology, structural characteristics and properties of PVA films and to adapt the suitable manufacturing technique of the ODFs to achieve appropriate HAL dissolution behaviour.

Influence of Casting Variables on Release Kinetics of Orally Disintegrating Film.

As a new form for supplying vitamin C, orally disintegrating films (ODFs) were developed C based on hyaluronic acid (HA) under varying casting conditions and the properties were analyzed. The films with different thicknesses (2, 3, and 8 mm, for CT2, CT4, and CT8, respectively) were produced by adjustments made to casting height. Two types of 8 mm thick ODFs produced by single or double casting (4 + 4 mm for CTD4+4) methods were also compared. As film thickness increased, water vapor permeability and tensile strength also increased. Even at equal thickness, manufacturing with double casting exhibited a stronger texture and reduced disintegration compared to single casting. All ODFs met the World Health Organization's recommended daily vitamin C intake (45 mg/day) with a single sheet. Films showed over 80% dissolution in various solvents, adhering to the Hixson-Crowell cube root law, indicating vitamin C release occurred via porous penetration of the eluate. For CT2, CT4, and CTD4+4, vitamin C release was primarily governed by diffusion within the gel matrix and HA erosion. However, for CT8, HA erosion-induced release somewhat dominated. Based on the sensory test, it seems desirable to adjust the thickness of the film to 2 or 4 mm, because a thickness greater than that increased the foreign body sensation due to prolonged residence in the oral cavity.

Development of soy protein isolate-based orally disintegrating film: Improvement of disintegration speed, mechanical properties, and thermal stability by β-Cyclodextrin

The effect of β-Cyclodextrin (β-CD) at different concentrations (0–20% w/w) on the function and properties of soy protein isolate (SPI)-based orally disintegrating films (ODF) was studied. The results of moisture content and contact angle indicate that the inclusion of β-CD enhances the moisture content and surface hydrophilicity of ODF. The thickness ODF samples is between 0.031 and 0.041 mm. Due to the addition of β-CD, ODF disintegration rates increased by 47.86%–64.62%. Scanning electron microscope, and mechanical analysis show that ODF with a β-CD concentration of 10% w/w has the best performance, presenting the smoothest surface, maximum tensile strength (TS) and elongation at break (EB). FTIR spectrum results show that there are physical entanglements and hydrogen bonding interactions between SPI and β-CD, and appropriate concentrations of β-CD (5% w/w and 10% w/w) can transform random coils into β-sheets. Once the concentration exceeding 10% w/w, β-CD will crystallize and precipitate on the ODF surface, which weakens the mechanical properties of the ODF and the strength of the SPI network structure. Thermogravimetric test results show that β-CD improves ODF thermal stability. This research offers a significant theoretical foundation for the advancement of ODF that are protein-based and not hydrolyzed.

Oral fast-dissolving risperidone loaded electrospun nanofiber drug delivery systems for antipsychotic therapy

Risperidone is an antipsychotic drug classified as BCS Class II with low solubility at physiological pH and orally used in the treatment of schizophrenia. Electrospinning is one of the newest fabrication methods used for the development of fast soluble drug delivery systems. In this study, an orally disintegrating film (ODF) formulation of risperidone was developed with green electrospinning technique. Different molecular weight polyethylene oxide (PEO) as a polymer and xylitol or Kollidon VA64 as a disintegration agent were used for the preparation of formulations. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) analyses were conducted as part of pre-formulation studies to identify possible incompatibilities in formulation components. We characterized ODFs based on their mechanical properties, shape and diameter of nanofibers, disintegration behavior, and in vitro dissolution profiles. A few wrinkles appeared on the surface of fibers prepared with xylitol, but a smooth surface was evident on Kollidon VA64 fibers. Disintegration studies performed in the simulated oral environment showed that ODFs disintegrate in as little as 1 s. The dissolution behavior of developed ODFs and commercial products was compared with a dissolution study in distilled water. The chosen formulations had acceptable mechanical properties with much faster dissolution compared to the commercially available product. In this study, risperidone ODF formulation was successfully produced and characterized. The study showed that risperidone-loaded nanofibers could provide a promising alternative to conventional oral dosage forms like tablets and capsules.

Orally Disintegrating Film: A Review of Its Formulation and Manufacturing Method

Oral route drug delivery system is still considered as the most convenient and patient friendly drug delivery route. Over the decades, many research has been performed to improve the functionality oral dosage form. Orally disintegrating film (ODF) is a newer oral drug delivery system, which is in the form of a thin film that will disintegrate in the oral cavity within a matter of seconds. The aim of this review paper is to recap ODF, its benefits, formulation contents and manufacturing method. With more research and development work has been conducted on ODF, the dosage form is expected to be manufactured and scaled up to be commercializable products to be sold in the market.

Synergistic modulation of chitosan on the mechanical and disintegration properties of pre-gelatinized waxy corn starch orally disintegrating film

The inconsistency between good mechanical properties and rapid disintegration characteristic is a challenge for starch-based orally disintegrating films (ODF). In order to improve the mechanical and disintegration performances of the films, chitosan/pre-gelatinized waxy corn starch (PWCS) ODF was fabricated and investigated for physical properties, surface micromorphology and crystallinity. The results showed that the mechanical properties of the composite films were improved (6.55 MPa ± 1.22 MPa, 18.11% ± 2.34%) while the fast disintegration characteristic (<30 s) was still maintained. During the film-forming process, the retrogradation of PWCS chains was hindered by chitosan molecules and the polar groups were exposed, enhancing the plasticity and hydrophilicity of the composite films. There was a synergistic effect between chitosan and PWCS. In addition, the microscopic images indicated that the high compatibility of chitosan and PWCS caused a homogeneous surface for the composite films. However, PWCS aggregated when the concentration of chitosan exceeded 20%, which increased the short-range order and crystallinity of PWCS in the composite films. The study provided a theoretical feasibility for the development of novel oral carrier platform.

Impact of calcium addition on the characteristics of hyaluronic acid-based oral films for vitamin D supplementation

An orally disintegrating film (ODF) was developed using hyaluronic acid as a base material, along with incorporation of vitamin D and varying amounts of calcium citrate. Increasing calcium amount within ODF resulted in higher opacity of the film, and stiffer texture. Microscopic examination of calcium-added films revealed consistently rough surfaces and cross-sections with irregular roughness. The moisture content and water vapor permeability were found to be higher in calcium-added films than in control films, however there was no significance by calcium amount. The content analysis indicated a loss of 32.66–46.16% of vitamin D and 8.05–13.53% of calcium in a sheet of ODF, which could be attributed to the formation of new chemical bonds among HA, vitamin D and calcium based on the result of FT-IR. In this study, it was successfully developed an ODF containing both vitamin D and calcium. However, unlike vitamin D, which can be added in recommended quantities within a single ODF, the addition of the insoluble bulk mineral, calcium, is limited, indicating that addition of plasticizer or technologies may be required to achieve an adequate amount of calcium incorporation into the ODF.

ORODISPERSIBLE FILM FABRICATION BY HOT MELT EXTRUSION FOR DENTAL PAIN AMELIORATION BY QUALITY BY DESIGN APPROACH

Surgical dental procedures cause pain and inflammation leading to temporary restriction of the movement of the oral cavity. Consumption of analgesic medications in the form of tablets or dispersible tablets causes compliance issues due to the compromised movability of the mandibular joint. An Orally Disintegrating Film (ODF), due to its pliability and compact size, can be a patient compliant tool for management of postoperative dental pain over parenterally administered opioids, conventional as well as orodispersible tablets of steroids or NSAIDS. Due to the inadequacies involved in solvent-casting, an unmet need exists for a continuous, eco-friendly and patient compliant process of manufacturing. The present research work addresses the unmet need of a patient compliant delivery system containing ketorolac tromethamine by Hot Melt Extrusion. The ODF optimized by Quality by Design was found to be stable with excellent mechanical properties and provided superior release profile as compared to the equivalent marketed formulation.

Physicochemical and in-vitro release characteristics of vitamin C-loaded antioxidant orally disintegrating films with different catechin levels

To develop a convenient food formulation for supplying antioxidants, hyaluronic acid (HA)-based orally disintegrating film (ODF) containing vitamin C (Vit C) and catechin (CAT) with various molar ratios (Vit C:CAT, 1:0, 1:0.2, 1:0.4, 1:0.6, 1:0.8 and 1:1.0, by name of CAT0, CAT0.2, CAT0.4, CAT0.6, CAT0.8 and CAT1.0, respectively) were prepared, and the physico-chemical, and sensory properties of the films were analyzed. In addition, the release properties of the Vit C and CAT in the films were also evaluated. In the results, there was no significant difference in the moisture content among the films, but the thickness significantly increased with the CAT amount. The water vapor permeability (WVP) started decreasing at CAT0.4. For texture, the addition of CAT decreased tensile strength, and showed inverse relationship with film thickness. Also higher the CAT content was, the more brittle and fragile the texture obtained film. The vitamin C content in the film significantly decreased as the CAT content increased, whereas the antioxidant effects continued to increase with CAT content. In a sensory evaluation, CAT0.2 was the most preferred, followed by CAT0 and CAT0.4, and for those samples containing over 0.6 M ratio CAT, the acceptability dramatically decreased. Based on the above results, the most suitable molar ratio of Vit C:CAT was 1:0.4. As a result of the analysis of the release pattern of the optimized ODF (CAT0.4), both Vit C and CAT exhibited rapid release of over 70% within 30 and 20 min, respectively, in all simulated body fluids. So the prepared ODF can be considered as a suitable delivery formulation for convenient and fast-acting antioxidant.

Formulation and evaluation of orally disintegrating film (ODF) containing piperine-succinic acid cocrystal

Piperine is a type of alkaloid found in plants of the Piperaceae family, including Piper nigrum and Piper longum , which has numerous pharmacological properties and is being developed as a nutraceutical. However, its poor solubility makes delivering in effective doses for therapeutic purposes challenging. To overcome this limitation, the cocrystals of piperine and succinic acid was prepared, which are more soluble, and then formulated into orally disintegrating films (ODFs) for better delivery. The cocrystals were formed using the slurry method, while the ODFs were made using the solvent-casting method with different concentrations of hydroxypropyl methylcellulose (HPMC) and polyethylene glycol (PEG) 400. The resulting films were evaluated for various parameters, such as their organoleptic characteristics, weight and thickness uniformity, pH, moisture content, swelling properties, and disintegration time. The results showed that the ODF with 6% HPMC as a film-forming polymer and 0.6% PEG 400 as a plasticizer loaded with 10 mg of piperine in the form of piperine-succinic acid cocrystal was the best formula. This ODF formulation disintegrated in less than one minute and was found to be a good film with uniform content.

Eggshell Membrane Based Turmeric Extract Loaded Orally Disintegrating Films.

The increasing interest in using natural bioactive compounds as new drug candidates due to their low solubility led to designing and developing novel drug delivery systems. Out of those, orally disintegrating films (ODFs) are a very eminent drug delivery system among pediatrics and geriatrics. In our study, the solvent casting method was used to prepare eggshell membrane-based and turmeric extract loaded orally disintegrating films. Characterization of the prepared films was done with FTIR, AFM, and SEM analysis. The release profile of the turmeric extract was determined and fitted to the mathematical models. AFM results showed that the best interaction between components was achieved in Film 2. The highest cumulative release percentage was obtained for the film with 7.5% (w/w) turmeric extract (Film-2) as 41.98%, based on the HPLC measurements. The Higuchi model was the best-- fitted model for Film 2. In this study, SEP and CMCH were used for the first time as biopolymers to prepare the orally disintegrating film. Turmeric extract was successfully integrated into films prepared from SEP and CMCH.

Electrospun orally disintegrating film formulation of telmisartan

Telmisartan (TEL) is an antihypertensive BCS class II drug with low solubility at physiological pH. However, the solubility of TEL increases with the presence of an alkalizer. Electrospinning is one of the most recent techniques for the solubility enhancement studies. In this study, an electrospun orally disintegrating film (ODF) formulation of TEL was developed with L-arginine and polyvinylpyrrolidone K90 (PVP), and its characterization studies were performed. Preformulation studies were performed to investigate possible incompatibilities in the components of formulation with differential scanning calorimetry (DSC) and Fourier transform infrared spectrometer (FT-IR) analyses. ODFs were characterized in terms of drug content and uniformity, mechanical properties, fiber shape and diameter and in vitro dissolution profile. Smooth nanofibers without any beads were obtained. The dissolution rate of the TEL significantly increased. The chosen formulation had acceptable mechanical properties with much faster dissolution compared to the commercially available product. Developed ODF and marketed product were compared with a dissolution study in phosphate-buffered solution (pH 7.4). ODF and marketed product both reached 100% release in the 45th minute, and ODF results showed that ODF had much faster release than marketed product. In this study, TEL ODF formulation was successfully produced and characterized.

Efficacy of orally disintegrating film vs intravenous ondansetron in preventing postoperative nausea and vomiting in middle ear surgeries under general anaesthesia

Introduction: Ondansetron is widely used perioperative antiemetic. In this study, we have assessed the anti-emetic efficacy of orally disintegrating film (ODF) in middle ear surgeries, associated with higher incidence of PONV. Materials and Methods: We studied two doses of ODF (4 and 8 mg) and compared it with IV ondansetron and placebo. All 120 cases were done under general anesthesia with standard anesthesia technique. Results: Oral intake was significantly delayed in placebo group. (p= 0.001) During first 6hrs, the PONV score was significantly low (p Conclusion: We conclude that all patients undergoing surgeries of middle ear should receive prophylactic antiemetic. Ondansetron in the form of orally disintegrating film is an effective as well as safe choice for PONV prevention in middle ear surgery with 8 mg to be the desired dose as compared to placebo and IV ondansetron. Keywords: Postoperative nausea vomiting, Ondansetron, Orally disintegrating film, Middle ear surgery.

Formulation of Orally Disintegrating Films as an Amorphous Solid Solution of a Poorly Water-Soluble Drug.

The objective of the present study was to develop an orally disintegrating film (ODF) for a poorly water-soluble drug, phenytoin (PHT), using the cosolvent solubilization technique to achieve the amorphization of the drug, followed by the preparation of ODFs. Eleven formulations were prepared with different polymers, such as polyvinyl alcohol (PVA) and high methoxyl pectin (HMP) by the solvent casting method. The prepared films were subjected to characterization for weight variations, thickness, surface pH, disintegration time and mechanical strength properties. Then, differential scanning calorimetry, X-ray diffraction analysis and the drug release patterns of the selected films were evaluated. Among the prepared formulations, the formulation composed of 1% w/w of PVA, 0.04% w/w of sodium starch glycolate with polyethylene glycol 400, glycerin and water as cosolvents (PVA-S4) showed promising results. The physical appearance and mechanical strength properties were found to be good. The PVA-S4 film was clear and colorless with a smooth surface. The surface pH was found to be around 7.47 and the in vitro disintegration time was around 1.44 min. The drug content of the PVA-S4 film was 100.27%. X-ray diffractometry and thermal analysis confirmed the transition of phenytoin in the PVA-S4 film into a partially amorphous state during film preparation using the cosolvent solubilization approach. The resulting PVA-S4 film showed a higher dissolution rate in comparison to the film without a cosolvent. Overall, this study indicated the influence of cosolvents on enhancing the solubility of a poorly water-soluble drug and its film dissolution.

Preparation and evaluation of orally disintegrating film containing donepezil for Alzheimer disease

The present study intended to prepare orally disintegrating film (ODF) containing donepezil (DP) for the treatment of mild to moderate alzheimer disease. HPMC and HPC, glycerine were used as film forming agents, plasticizer, respectively. The ODFs were prepared by solvent casting method. The method was optimized with full factorial design considering the amount of film forming agents, the proportion of HPMC: HPC, amount of plasticizer as independent variables and tensile strength, elongation, folding endurance and disintegration time as dependent variables. Furthermore the studies of mechanical, drug release and bioavailability of the optimized DP-loading ODF formulation were performed. The results indicated the prepared film hold uniform, smooth film surface, non-sticky and disintegrated within 30 s, and over 85% of the drug dissolved in the first 5 min. And there was no significant difference between the optimized ODF formulation and the marketed one in cmax, tmax and AUC0-t.Current study suggested the optimized ODF formulation will be an effective alternative for commercially available dosage forms for the treatment of Alzheimer's diseases.

Comparative single-dose pharmacokinetics of sildenafil after oral and rectal administration in healthy beagle dogs

BackgroundSildenafil citrate, a highly selective phosphodiesterase type 5 inhibitor, is used to treat pulmonary hypertension (PH) in veterinary medicine. The objective of this study was to investigate pharmacokinetic profiles by oral administration of orally disintegrating film (ODF) and film coated tablet (FCT) formulations and rectal administration of ODF formulation in healthy dogs. Twelve healthy beagle dogs were administered four separate doses of sildenafil: FCT formulation 2 mg/kg orally, ODF formulation 2 mg/kg orally, ODF formulation 2 mg/kg rectally, and ODF formulation 10 mg/kg rectally. For 24 hours following administration, blood samples were collected and the plasma concentrations of sildenafil were assayed by liquid chromatography-tandem mass spectrometry.ResultsThere were no significant differences in all the pharmacokinetic parameters between FCT and ODF formulations when administrated orally. Cmax at the time of rectal administration was lower when the same dose was given as that orally administered. No serious systemic adverse events (AEs) were observed.ConclusionsThese findings suggest that sildenafil ODF formulation can be used as an alternative to FCT formulation in the treatment of canine PH patients; additionally, rectal administration of sildenafil ODF may be a beneficial treatment option for canine patients who are unable to receive medication orally.

Formulation design of hydroxypropyl cellulose films for use as orally disintegrating dosage forms

Hydroxypropyl cellulose (HPC) is a water-soluble polymer used as a binder during pharmaceutical tableting and granulation. HPC is also known as a base material for pharmaceutical film by virtue of its film formability with excellent plasticity.The aim of this study was to assess the applicability of HPC to orally disintegrating film (ODF) and to investigate optimization of the ODF formulation of HPC. The effects of the molecular weight of HPC and the addition of active pharmaceutical ingredients and excipients on the properties of ODFs prepared using HPC were evaluated. The results showed that a suitable grade of HPC as a base material for ODFs should be used in a suitable concentration in solution. The results also clarified that the disintegration time markedly decreased as the thickness of HPC films decreased. These properties could be controlled by adjusting the ingredients added to the formulation. While loading the film with ibuprofen prolonged the disintegration time, adding calcium carbonate particles to the film shortened it. These results demonstrated that HPC can be used as a base material for ODF applications.

An advanced technique using an electronic taste-sensing system to evaluate the bitterness of orally disintegrating films and the evaluation of model films

Taste detection systems using electronic sensors are needed in the field of pharmaceutical design. The aim of this study was to propose an advanced technique using a taste-sensing system to evaluate the bitterness of an orally disintegrating film (ODF) samples. In this system, a solid film sample is kept in the test medium with stirring, and the sensor output is recorded. Model films were prepared using a solution-casting method with a water-soluble polymer such as pullulan, HPMC, HPC or PVP as film formers, and donepezil hydrochloride and quinine hydrochloride as model bitter-tasting active pharmaceutical ingredients (APIs). The results showed that this advanced techniques could detect the emergence of bitterness along the time course. Increasing the amount of donepezil hydrochloride increased the sensor output. The sensor output was suppressed at the very early stage of the test, and then increased. Both the film thickness and the use of additives markedly affected the delay of the sensor output. The profile of the sensor output was accurately related to the release of APIs. It was concluded that this advanced technique could detect the onset of bitterness during the initial stage of ODF administration.

Characterization of low cost orally disintegrating film (ODF)

Abstract Orally disintegrating films (ODF) produced with a hydrophilic polymers are a thin and flexible material, wich disintegrate in contact with saliva and can vehicule bioactive materials. The aim of this study was to develop and characterize ODF formulation with potential to act as a carrier for different bioactives compounds prepared with low cost polymers. Gelatin (G), starch (S), carboxymethyl cellulose (CMC) and their blends (G:S, CMC:S, CMC:G, and CMC:S:G) were prepared by casting technique with sorbitol as a plasticizer. The formulations were characterized in terms of visual aspects, FTIR, SEM, mechanical characteristics, hygroscopicity, dissolution (in vitro and in vivo) and swelling index. FTIR analysis revealed that no interaction between polymers in ODF was observed. By SEM, it was possible to observe differences on surfaces by different polymers. ODF made with CMC and CMC:G presented higher water absorption (P<0.05) and higher swelling index probably due to the higher water affinity by CMC. Formulations with G, CMC:G and CMC:S:G presented the highest values of tensile strength (P<0.05). ODF prepared with S alone presented the highest disintegration time, the others formulations showed in vitro dissolution ranging from 5.22 to 8.50 min, while in vivo dissolution time ranged from 2.15 to 3.38 min. By the formulations made with G and blend of G:S and CMC:S:G it is possible to develop a ODF of low cost with desired characteristics being an alternative vehicle to deliver functional compounds for continuous use.