Orally Disintegrating Films Research Articles

Pre-gelatinized cassava starch orally disintegrating films: Influence of β-Cyclodextrin

The study investigated the interactions between pre-gelatinized cassava starch (PCS) and β-Cyclodextrin (β-CD) in the preparation process of orally disintegrating films (ODFs). The thermal properties, mechanical properties, surfaces micromorphology and FTIR spectra of the ODFs were measured. The moisture content, mechanical properties and surface hydrophilicity of the ODFs were improved after β-CD were incorporated in film matrix. Disintegration time was prolonged slightly due to the increase of thickness in ODFs containing β-CD. However, the disintegration time of all ODFs samples was shorter than 60 s. The results of thermal properties, atomic force microscope, and FTIR spectra indicated: β-CD promoted the uniform dispersion of PCS during stirring and the formation of more complete network structure. However, excessive β-CD blocked the aggregation of PCS chains. It promoted the mono-dispersion of PCS molecules and the formation of weakened network structure. The study will help to develop the new type vehicle platform of active ingredients via oral delivery.

Carboxymethyl cellulose-based orally disintegrating films enriched with natural plant extract for oral iron delivery

The aim of this work was to provide an alternative for iron intake using carboxymethyl cellulose (CMC)-based orally disintegrating films (ODF) containing ora-pro-nobis (OPN) extract or microparticles. The novelty is based on the use of iron from an alternative vegetable source into ODF systems employing only natural compounds. OPN is a native and underused plant that presents high contents of proteins and minerals. Different formulations of CMC-based ODF were produced employing the tape casting technique and characterised by colour parameters, contact angle, surface pH, mechanical properties, oral disintegration time, infrared spectroscopy, microstructure by scanning electron microscopy (SEM) and atomic force microscopy (AFM), and iron release. The results indicated the formation of hydrophilic systems with fast disintegrating times (<50 s) for all formulations. The release of iron occurred in a maximum time of 26 and 50 min for CMC-based ODF-microparticles and CMC-based ODF-OPN extract, respectively, following a Fickian diffusion mechanism. The systems developed could be a potential and innovative application for a vehicle of oral iron intake, facilitating the reduction of iron-related diseases in human health.

Oral Disintegrating Films – A Novel Approach for Patient Compliance

Oral disintegrating films (ODF) are recently being explored overcome the problem faced by pediatric and geriatric populations of swallowing the tablets. Oral disintegrating films disintegrate in the mouth cavity infraction of time and then they are to be swallowed. Remarkably, after getting swallowed by the patient, they should dissolve and release the drug in the GI track. The ODF is simply placed on the tongue or any oral mucosal tissue which makes the film wet, rapidly disintegrate and dissolve to immediate release of medication for oral absorption. It is the advance form of solid dosage form due to their flexibility and enhances the release rate of API within the seconds. There are various polymers used in ODF as an individual or in combination to obtain desirable properties such as Mechanical strength, Drug loading capacity, Drug release and Disintegration time. Depending on the content and type of polymer selected for the preparation of optimized formulation of ODF, which has to be disintegrate within a seconds after make in contact with mouth. ODFs are characterized for the quality parameters like Physical strength, Appearance, Drug release profile, Residual water content, Dose uniformity, Organoleptic characteristics and Stability. Thus, the oral disintegrating films can be a novel promising approach for patient compliance with faster onset of action.

An Updated Overview on Mucoadhesive Buccal Drug Delivery System

Among the various routes of drug delivery, the oral route is an attractive site for the delivery of drugs. The main advantages of these formulations are: drug targeting, sustained release, increased permanence time in the buccal mucosa, increased bioavailability, and decreased potential adverse effects and maintains constant blood levels for extended period of time. The buccal cavity was found to be the most suitable and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery. Buccal mucosa has a tremendous availability, which leads to direct access to systemic circulation through the internal jugular vein bypasses the drug from hepatic first pass metabolism. The main disadvantage of this route is Limited absorption area- the total surface area of the membranes of the oral cavity available for drug absorption is 170 cm2 of which ~50 cm2 represents non-keratinized tissues, including buccal membrane, the barrier function of the skin changes from one site to the other and from one person to other person with age and large dose of drug are difficult to be administered. Melt granulation is emerging technique and this technique used to increase the dissolution rate of poorly water-soluble drugs. Tablet molding technique: Tablets produced by the molding technique are easier to scale up for industrial manufacture than lyophilisation technique. Hot melt extrusion of film method: Hot melt extrusion has been used for the manufacture of controlled release matrix tablets, pellets and granules, as well as oral disintegrating films.

Anti-aging effect of an oral disintegrating collagen film: a prospective, single-arm study.

As the average life expectancy increases, skin aging and wrinkles due to photoaging have gained attention. Collagen is closely involved in the process of skin aging. Among the potential methods of drug delivery to the skin, oral disintegrating films show promise for their ability to bypass the loss of active components that is typical of drug absorption via oral administration. This study was conducted to investigate the effect of an oral disintegrating collagen film on skin aging. We performed a prospective, single-arm study in a cohort of 22 women to assess the anti-aging effect of a novel oral disintegrating film containing collagen applied daily over a 12-week period. We measured the clinical indicators of skin integrity and performed immunofluorescence and high-performance liquid chromatography analyses of an exvivo oral mucosa model to compare the absorption rates of collagen films and conventional oral tablets via the mucosa. We found that the oral disintegrating collagen film reduced skin wrinkle depth and number and significantly increased skin elasticity and density. The novel mode of delivery of collagen via oral disintegrating films has a clinically potential anti-aging efficacy and is safe and convenient for daily use.

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.

Development and characterization of pullulan-based orally disintegrating films containing amlodipine besylate

The aim of this study was to prepare pullulan-based orally disintegrating films (ODFs) containing amlodipine besylate, an anti-hypertensive drug, by the solvent casting method. For this purpose, nine different ODF formulations (F1-F9) were prepared by using different plasticizers (glycerol, sorbitol, propylene glycol) and different superdisintegrants (croscarmellose sodium, sodium starch glycolate, crospovidone). FD&C Green and aspartame were used as coloring agent and sweetener, respectively. According to the results of preformulation studies, the optimum ODF (F9) was determined and various characterization studies such as uniformity of mass, film thickness, surface pH of films, and mechanical properties (such as elongation at break, tensile strength, Young's modulus, and folding endurance), moisture content, disintegration time, uniformity of content and dissolution test, X-ray, DSC, SEM and short term stability analysis were performed on this formulation. Cytotoxicity and permeability studies for the F9 formulation were performed on the human epithelial colorectal adenocarcinoma (Caco-2) cell line. The formulation F9 had appropriate morphological and mechanical properties and disintegrated within 51.3 s according to the petri dish method, and 28.8 s according to the drop method. Dissolution studies revealed that 78.1 % of amlodipine besylate was dissolved in 20 min from F9 formulation. Cell culture studies showed that the formulation had no significant toxic effect on the Caco-2 cells. Also, there was no significant difference between the Caco-2 permeabilities of amlodipine besylate powder and amlodipine besylate ODFs. As a result of all these studies, we suggest to use the pullulan based amlodipine besylate ODFs to enhance ease of administration and patient compliance.

Mechanical characteristics of orally disintegrating films: Comparison of folding endurance and tensile properties.

The tensile test is the most widely used method for testing the mechanical characteristics of orally disintegrating films (ODFs). The other available test is the folding endurance (FE) test, which is more suitable for clarifying the actual strength during the manufacturing and dosing. However, the FE test is performed manually, and the FE number it generates has not been adequately analyzed as an index. The aim of this studies were to establish an automatic method for determining the FE number, and to compare the resulting FE numbers with the tensile properties. For this purpose, a desktop-model endurance test machine was used. First, the operating conditions-i.e., the folding angle, the folding speed and the weight requirement were optimized using ODF models. Secondly, the FE of ODFs prepared from three film formers (HPMC, HPC, and PVA) and with insoluble particles (calcium carbonate), plasticizers (glycerin) and APIs (acetaminophen), was evaluated and compared with the tensile properties. Lastly, the commercial ODFs were investigated. The results showed that our automatic system could be successfully used to determine the FE characteristics of ODFs. FE was suggested to relate to not only the strength but also the elongation during the tensile test.

Antioxidant and anti-inflammatory properties of orally disintegrating films based on starch and hydroxypropyl methylcellulose incorporated with Cordia verbenacea (erva baleeira) extract

Cordia verbenacea (erva baleeira) is a plant used in indigenous folk medicine. Due to its pharmacological properties (antioxidant and anti-inflammatory), it can be used in the development of herbal medicines by different forms of administration such as orally disintegrating films (ODFs), which would facilitate the systemic release of its active ingredients. Considering the properties of the C. verbenacea and the advantages of ODFs, the objective of this work was the potential development of ODFs with antioxidant and anti-inflammatory properties. The polymeric matrices were produced based on starch and hydroxypropyl methylcellulose and additives with different C. verbenacea extract concentrations in order to obtain concentrations of 0.25, 0.50 and 0.75 mg flavonoids/ODF. The films were characterized by microscopy, infrared spectroscopy, mechanical properties, mucoadhesiveness, in vitro disintegration, in vitro release of flavonoids, antioxidant, and anti-inflammatory activities of the films. The ODFs showed good antioxidant activity and high anti-inflammatory capacity with inhibition of COX-2 enzyme. The stability study demonstrated the conservation of flavonoids and also the maintenance of the anti-inflammatory capacity of ODFs. This study demonstrated that orally disintegrating films have high potential for the delivery of natural bioactive compounds and the maintenance of their pharmacological properties.

Orally disintegrating films based on gelatin and pregelatinized starch: new carriers of active compounds from acerola

This study aimed to produce orally disintegrating films (ODFs) based on pregelatinized starch and gelatin with the incorporation of acerola powder and to evaluate the effect of the macromolecule concentration on the properties of the films. No ODFs had insoluble particles, and microstructure analysis by atomic force microscopy showed that higher starch concentrations led to greater surface heterogeneity and roughness. Starch inclusion in the films enhanced the hydrophilicity of the material (producing lower contact angle values). These factors, along with higher levels of starch, probably contributed to the favorable disintegration time, as observed by the lower values from in vitro and in vivo analyses. The FTIR spectra of the ODFs demonstrate predominant presence of carbohydrates and proteins, showing good interaction between them. In addition, the antioxidant capacity results showed that, after 50 days of storage under drastic conditions (75% relative humidity and 40 °C), the ODFs retained at least 60% of their antioxidant capacity. Therefore, the ODF containing acerola powder represents a promising system for use in active compound delivery.

Novel use of insoluble particles as disintegration enhancers for orally disintegrating films

The most important issue in the design of orally disintegrating films (ODFs) is the control of the ODFs' disintegration properties. A better understanding of the mechanisms of ingredients used to promote or disturb the disintegration time of ODFs would improve the development of ODF formulations. Here we focused on the advantage of adding insoluble particles (IPs) to improve the disintegration times of ODFs. We also verified the undesirable impact of the use of IPs on the mechanical properties of ODFs. We used hydroxyproplyl methylcellulose (HPMC), which is one of the most commonly used film-forming polymers for ODFs, as a film former. Films were prepared using the solution/solvent casting method. Microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and silica with different particle sizes and shapes were added in the film formulations as IPs. As expected, the addition of IPs shortened the disintegration times of the films. The larger particles had a greater impact compared to the smaller particles. However, the addition of larger particles decreased the films’ tensile strength. Our results demonstrate the effectiveness of IPs for shortening the disintegration times of HPMC films loaded with active pharmaceutical ingredients.

Formulation Development and Evaluation of Taste Masked Oral Disintegrating Films of Atenolol by Using Natural Polymers

Fast dissolving/disintegrating films/tablets have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical area. Particularly the fast dissolving drug delivery systems formulated with natural polymers have more demand because natural materials like gums and mucilages have been extensively used in the field of drug delivery for their easy availability, ease administration, non toxicity, non irritant nature etc. Atenolol is β1-selective adrenergic blocking agent and widely used in the treatment of hypertension and angina pectoris. It has a bioavailability of 40-50%. The main objective of the study was to formulate taste masked oral fast disintegrating films of Atenolol to achieve a better dissolution rate by improving the bioavailability of the drug and providing quick onset of action thereby enhancing patient compliance. Oral FDF prepared by solvent casting method using water and 95% ethanol as solvents and HPMC as film forming polymer. PEG 400 was the selected plasticizers, Natural and synthetic superdisintegrants such as croscarmellose sodium (CCS), sodium starch glycolate (SSG) and fenugreek mucilage alone and also in combinations was incorporated to achieve quick onset of action, is to increase the water uptake with in shortest wetting time and there by decrease the disintegration time. The prepared films were evaluated for the drug content, weight variation, film thickness, disintegration time, folding endurance, percentage of moisture content and in vitro dissolution studies and taste mask studies on healthy human volunteers. Among all, the formulation F5 was found to be best formulation which releases 98.89% of the drug within 15 min and disintegration time is 59 sec. which was significantly high when compared to other formulation. When the regression coefficient values compared, it was observed that ‘r’ values of formulation F5 was maximum i.e 0.890 hence indicating drug release from formulations was found to follow zero order drug release kinetics.

INCORPORATION OF ACTIVE COMPOUNDS FROM MANGO PEEL (Mangifera indica L. Cv. “Tommy Atkins”) INTO CORN STARCH–BASED ORAL DISINTEGRATING FILMS

This study aimed to evaluate the incorporation of mango peel extract, as a source of natural active compounds, in oral disintegrating films (ODF). The starch–based ODF were produced using a casting technique with glycerol as a plasticizer. Four formulations were tested by varying the amount of extract in the films: control, ODF 20, ODF 40, and ODF 60 (0, 20, 40, and 60 g of extract per 100 g of film0genic solution, respectively). The surface pH, disintegration time, total phenolic content, antioxidant activity, release of total phenolic content, and stability of the ODF was evaluated. All formulations studied could be classified as fast disintegrating films and source of phenolic compounds. ODF 60 showed the largest, most stable release of phenolic compounds under accelerated conditions (40 °C and 75% relative humidity). Thus, corn starch–based oral disintegrating films containing mango peel extract represent a useful vehicle for the delivery of phenolic compounds in the oral cavity.

Effect of starch and hydroxypropyl methylcellulose polymers on the properties of orally disintegrating films

Considering the advantages of orally disintegrating films as alternative pharmaceutical dosage forms, the objective of this work was to develop and evaluate different formulations of orally disintegrating films based on pre-gelatinised starch (%S) and hydroxypropyl methylcellulose (%HPMC), with suitable mechanical and disintegrating characteristics. The 90S:10HPMC, 80S:20HPMC and 70S:30HPMC formulations were selected by scanning electron microscopy for mechanical characterisation and disintegration. The increase of HPMC in the matrix reduced the tensile strength and caused the films to be less mucoadhesive. The films showed in vitro disintegration times of less than 30 s. During the in vivo disintegration, the formulation 80S:20HPMC presented the best sensation in the mouth, according to the tasters. The study showed the possibility of producing oral disintegrating films based on starch and HPMC, with the formulation 80S:20HPMC as the most suitable for further studies on the incorporation of active ingredients for oral release.

Orally Dispersible films a new platform for Drug Delivery System

Orodispersible films are thin films, when in contact with saliva gets rapidly disintegrate and dissolve to release the medication for oral mucosal absorption. The film plays a major alternative approach to conventional oral dosage form like tablets, capsule, syrups. The thin films are considered to be convenient to swallow,self-administrable, rapid disintegration, dissolution and quick onset of effect which make it as a versatile platform for effective drug delivery. Oral disintegrating films have superiority over the tablet formulations because there is no risk of chocking and friability. Compared with the traditional dosage forms this dosage forms give greater advantage as it provides a new way for the pediatrics, geriatrics, bedridden patients etc. Several types of approaches are there for preparation of the films. Mostly solvent casting method is used for the development of orodispersible films. For the development of dosage forms polymers and plasticizers along with other excipients are used. Usually hydrophilic polymers are used for the preparation. The design of the film requires comprehensive knowledge of pharmaceutical and pharmacological properties of drug and polymers along with the manufacturing therefore the aim of the review provide an overview of preparation the film The present review focus on benefit, composition, approaches for formulation and evaluation of the Orally dispersible film.

Design of a new disintegration test system for the evaluation of orally disintegrating films

In the design of the orally disintegrating films (ODFs), it is important to determine the disintegration time (DT) precisely and properly. These films’ DTs are usually assessed by a disintegration test defined in the pharmacopoeias, but under the conditions of such tests, a much larger volume of water is used and a stronger up-down movement is applied compared to the conditions of the human oral cavity. Here we developed and tested our new disintegration test system for ODFs. We chose a disintegration test device (the Tricorptester®, Okada Seiko, Tokyo) for orally disintegrating tablets. This device enabled the mechanical dropping of the test medium. We designed an exclusive fixture for ODFs, made an opening in the center of the fixture, and optimized the size of the opening (i.e., the cell). We also investigated that test conditions including the types of test media, the dropping height, flow rate, dropping methods, and medium holding methods. With a passage sensor attached to the Tricorptester, the device was able to automatically detect the DTs of ODFs. We thus successfully developed a new disintegration test system and optimized the operating conditions. Using this system, model ODFs and the commercial ODFs can be properly evaluated.

FORMULATION AND EVALUATION OF ORAL DISINTEGRATING FILM OF ATENOLOL

Objective: The main objective of the study was to formulate the oral disintegrating films loaded with atenolol by solvent-casting method and to carry out its evaluation studies.Methods: The films were prepared using the film-forming hydrophilic polymer like hydroxypropyl methylcellulose (E-5) and super disintegrant like pectin in various proportions.The formulated oral films were characterized for Fourier transform infrared (FTIR) and morphological evaluations. Various physicochemical parameters such as weight variation, folding endurance, surface pH, in vitro disintegration, and in vitro dissolution studies were carried out.Results: FTIR studies revealed that there was no drug-polymer interaction. The morphological evaluation of films showed that all the films were homogenous and transparent. The folding endurance test ensured that the films had sufficient brittleness and by weight variation test, it was inferred that all the films were within the deviation. The surface pH study showed the pH of the films was around neutral pH. The drug was well distributed in all the films. The films disintegrated within 120 s and the fastest being disintegrated in 30 s. Based on all the evaluation parameters, F6 had shown optimal performance and remarkable increase in drug release of 94.38% in 2 min.Conclusion: Thus, formulated oral disintegrating films can be termed as an alternative approach to deliver atenolol.

Hydroxypropyl cellulose-based orally disintegrating films of promethazine HCl for the treatment of motion sickness

Purpose: To prepare and characterize orally disintegrating films (ODFs) of promethazine hydrochloride (HCl) for prompt treatment of motion sickness.Methods: Films were prepared by solvent casting method using hydroxypropyl cellulose (HPC) as film former and glycerin as plasticizer along with a saliva stimulating and sweetening agent. Nine different film formulations were prepared and evaluated for their characteristics including thickness, disintegration time, tensile strength and drug release behavior.Results: The prepared films were transparent and slightly sticky in nature with thickness that ranged from 0.22 mm to 0.29 mm and tensile strength of 0.56 N/cm² to 2.49 N/cm². The disintegration time of film formulations ranged from 26.3 to 52.7 s and a majority of formulations released approx. 80 % of the drug within 10 min with a non-Fickian diffusion pattern.Conclusion: The study concludes that the orally disintegrating films of promethazine HCl can be prepared using HPC as film former.Key words: Orally disintegrating films, Promethazine, Solvent casting, Motion sickness

Gelatin/starch orally disintegrating films as a promising system for vitamin C delivery

Orally disintegrating films (ODFs) may disintegrate rapidly or slowly when in contact with saliva, acting as carriers of different compounds. The objective of this work was the production of gelatin and starch ODFs as vehicles of vitamin C obtained via a spray-drying method from camu-camu powder. ODFs were produced by mixing gelatin and/or starch as main components, sorbitol as plasticizer, and the powder from camu-camu as an active compound. The ODFs were characterized regarding their visual qualities, mechanical properties, contact angle, surface pH, disintegration time (in vitro and in vivo), ascorbic acid degradation, antioxidant activity stability and sensory attributes. The ODFs were homogeneous and easy to handle. An increased starch concentration in the ODF promoted a significant increase of hydrophilicity and thus, the decrease of in vitro disintegration time. The ODFs also showed a fast in vivo disintegration time. Moreover, the evaluation of the sensory attributes demonstrated that ODF consumption was palatable to the panelists. Therefore, ODFs with camu-camu extract can be used as an efficient and natural supplementary source of vitamin C and as a potential carrier of antioxidant compounds.

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.