Orodispersible Films Research Articles

Formulation and characterization of tadalafil-loaded orodispersible films with enhanced dissolution rate and membrane permeability

The low solubility of tadalafil (TDF) normally retards the dissolution rate and permeability of the drug in oral mucosa and gastrointestinal tract. The aim of this study was to optimize and evaluate novel orodispersible films (ODFs) loaded with TDF or micronized TDF (MTDF) to enhance the solubility and permeability of the drug. The TDF(or MTDF)-loaded ODFs with polyvinyl alcohol 1788 as a film-forming material, sodium alginate as a disintegrant, polyethylene glycol 400 as a plasticizer, and polysorbate 80 (Tween 80) or sodium lauryl sulfate (SLS) as a surfactant was prepared by using a solvent casting method. In addition, the formulation composition of TDF-loaded ODFs was also optimized in terms of appearance, thickness, disintegration time, mechanical properties, and dissolution rate of films. The SLS-incorporatedODFs showed more reliable dissolution profiles than Tween 80-incorporated ODFs in pH 7.4 PBS (0.5% SLS and 1% Tween 80) as compared to commercial tablet (Cialis®). The dissolution rates of optimal TDF-loaded ODFs (F11) at pH1.2 and pH7.4 were 68.74% and 74.81% at 15 min, 83.04% and 84.95% at 30min, respectively. Compared with Cialis® and F11, MTDF-loaded ODFs (F12) showed faster dissolution rate at 10 min in pH 7.4 PBS (0.5% SLS). There was no significant difference in the in vitro permeability between F11 and F12 in the media containing Tween 80. However, the permeability of F12 was higher than that of F11 if Tween 80 was absent in the dissolution media. In conclusion, novel TDF or MTDF-loaded ODFs were successfully formulated and the ODFs incorporated with MTDF showed higher drug dissolution and membrane permeability, indicating that the ODFs formulated with MTDF may be an alternative to commercial tablets for the treatment of male erectile dysfunction.

Hydroxypropyl Methylcellulose Orodispersible Film Containing Desloratadine for Geriatric Use: Formulation and Evaluation.

Oral strip is very similar to thin strip of postage stamp in shape, size and thickness. The strip is designed to be placed on the tongue or any oral mucosal tissue which immediately gets wet and hydrated after being in contact with the saliva. Desloratadine is one of the better- known second-generation antihistamines that has been studied for being effective in relieving the allergic nasal and skin symptoms. The aim of this study is to develop desloratadine orodispersible film (ODF) with fast disintegration time and suitable mechanical strength to treat allergic symptoms in geriatric patients in order to increase compliance and convenience. Solvent casting method using hydroxypropyl methylcellulose (HPMC) as the film forming polymer was applied. Polyethylene glycol 400 (PEG 400) and glycerol (Gly) were used as the plasticizers and citric acid (CA) was used as saliva stimulating agent. The resultant films were evaluated for disintegration time, folding endurance, surface pH, weight variation, thickness, surface morphology using scanning electron microscopy, drug content, content uniformity, moisture loss, moisture uptake, and drug-excipient compatibility using DSC and FT-IR. All the selected films started to disintegrate in less than 14 seconds. Selected optimum films exhibited good mechanical properties with a folding endurance value greater than 100. The uniformity in weight, thickness, and drug content in the selected films was obtained. Surface pH was within the normal range (6.4 - 6.8). A smooth surface of the films was obtained and drugexcipient compatibility was proved using DSC and FT-IR. The dissolution test was done for optimum film formulations by simulating the oral cavity physiological conditions using the conventional dissolution test apparatus. More than 87% of the drug was released by the 4th minute. Orodispersible film of desloratadine was successfully prepared by solvent casting method in order to improve the disintegration/dissolution of the drug in oral cavity and hence better patient compliance and effective therapy.

Preliminary Study on the Development of Caffeine Oral Solid Form 3D Printed by Semi-Solid Extrusion for Application in Neonates.

Apnea of prematurity can be treated with a body-weight-adjusted dosage of caffeine. Semi-solid extrusion (SSE) 3D printing represents an interesting approach to finely tailor personalized doses of active ingredients. To improve compliance and ensure the right dose in infants, drug delivery systems such as oral solid forms (orodispersible film, dispersive form, and mucoadhesive form) can be considered. The aim of this work was to obtain a flexible-dose system of caffeine by SSE 3D printing by testing different excipients and printing parameters. Gelling agents (sodium alginate (SA) and hydroxypropylmethyl cellulose (HPMC)) were used to obtain a drug-loaded hydrogel matrix. Disintegrants (sodium croscarmellose (SC) and crospovidone (CP)) were tested for get rapid release of caffeine. The 3D models were patterned by computer-aided design with variable thickness, diameter, infill densities, and infill patterns. The oral forms produced from the formulation containing 35% caffeine, 8.2% SA, 4.8% HPMC, and 52% SC (w/w) were found to have good printability, achieving doses approaching to those used in neonatology (between 3 and 10mg of caffeine for infants weighing approximately between 1 and 4kg). However, disintegrants, especially SC, acted more as binder/filler, showing interesting properties to maintain the shape after extrusion and enhance printability without a significant effect on caffeine release.

Orodispersible Film Based on Maltodextrin: A Convenient and Suitable Method for Iron Supplementation.

Orodispersible film (ODF) is an innovative dosage form used to administer drugs and nutrients, designed to disintegrate or dissolve in the oral cavity without needing water. One of the advantages of ODF is that it is suitable for administration in older people and children who have difficulty swallowing because of psychological or physiological deficiencies. This article describes the development of an ODF based on maltodextrin, which is easy to administer, has a pleasant taste, and is suitable for iron supplementation. An ODF containing 30 mg of iron as pyrophosphate and 400 µg of folic acid (iron ODF) was developed and manufactured on an industrial scale. The kinetic profile for serum iron and folic acid upon consumption of ODF compared with a Sucrosomial® iron capsule (known for its high bioavailability) was evaluated in a crossover clinical trial. The study was conducted in nine healthy women, and the serum iron profile (AUC0-8, Tmax, and Cmax) of both formulations was defined. Results showed that the rate and extent of elemental iron absorption with iron ODF was comparable to that obtained using the Sucrosomial® iron capsule. These data represent the first evidence of iron and folic acid absorption concerning the newly developed ODF. Iron ODF was proven to be a suitable product for oral iron supplementation.

The potential role of the novel orodispersible film from rice polymer loaded with silkworm pupae hydrolysate and the combined extract of holy basil and ginger for the management of stroke with stress

The prevalence of stroke under stress conditions is rising and the severity of stroke is increasing. Owing to the limitation of the current therapeutic strategy, a novel effective strategy for treating this condition is needed. In this study, we explored the neuroprotective effect of an orodispersible film derived from a rice polymer loaded with silkworm pupae and the combined extract of holy basil and ginger (JP1). Male Wistar rats weighing 200–250 g were administered JP1 at the doses of 1, 10, and 100 mg/kg BW 45 min prior to an exposure to a 6-h immobilization stress for 14 days. Permanent, occlusion of the right middle cerebral artery (MCAO) was performed, and JP1 was administered continually for 21 days after MCAO. Assessments of the brain infarction volume, oxidative stress, inflammation, and apoptosis in the cerebral cortex were carried out 24 h after MCAO. Neurological severity scores were also determined for the rats every 7 days after MCAO until the end of the study period. The results clearly showed that all doses of JP1 decreased the brain infarct volume, oxidative stress, inflammation, and apoptosis and improved neurological deficits. Therefore, JP1 is a potential novel neuroprotective supplement for combating ischemic stroke under stress conditions. However, a clinical trial is essential to confirm this beneficial effect.

Preparation and Evaluation of Caffeine Orodispersible Films: The Influence of Hydrotropic Substances and Film-Forming Agent Concentration on Film Properties.

This study aimed to develop caffeine (CAF) orodispersible films (ODFs) and verify the effects of different percentages of film-forming agent and hydrotropic substances (citric acid-CA or sodium benzoate-SB) on various film properties. Hydroxypropyl methylcellulose E 5 (HPMC E 5) orodispersible films were prepared using the solvent casting method. Four CAF-ODF formulations were prepared and coded as CAF1 (8% HPMC E 5, CAF), CAF2 (8% HPMC E 5 and CAF:CA-1:1), CAF3 (9% HPMC E 5 and CAF:CA-1:1), and CAF4 (9% HPMC E 5 and CAF:SB-1:1). The CAF-ODFs were evaluated in terms of disintegration time, folding endurance, thickness, uniformity of mass, CAF content, thickness-normalized tensile strength, adhesiveness, dissolution, and pH. Thin, opaque, and slightly white CAF-ODFs were obtained. All the formulations developed exhibited disintegration times less than 3 min. The dissolution test revealed that CAF1, CAF2, and CAF3 exhibited concentrations of active pharmaceutical ingredients (APIs) released at 30 min that were close to 100%, whilst CAF4 showed a faster dissolution behaviour (100% of the CAF was released at 5 min). Thin polymeric films containing 10 mg of CAF/surface area (3.14 cm2) were prepared.

Pediatric Drug Development Process: A Review

This review includes New Formulation approaches to improve Pediatric compliance such as Mini tablets, 3D printing, Orodispersible films, Chewable tablets. Various strategies to improve patient adherence such as ‘nipple shield’ delivery system, dry solid formulations to be converted to liquid at the point of administration, pill swallowing cups, Medicated dosing straw. It is important to formulate pediatric medicines that are tailored to a child’s age, size, physiological condition, and treatment requirements. Legislations for pediatric formulation to ensure that products to treat pediatric patients are appropriately authorized for use in the pediatric population, minimize the worst effect of Off-label medication and to improve the information available on the use of these products in the various pediatric populations. Also, the review consists of Information on legislative obligation and requirement, current State, challenges and effect of regulations. Recent progress has been made in the development of pediatric formulations due to new regulations, additional funding opportunities, and collaborative research initiatives.

Predicting pharmaceutical inkjet printing outcomes using machine learning

Inkjet printing has been extensively explored in recent years to produce personalised medicines due to its low cost and versatility. Pharmaceutical applications have ranged from orodispersible films to complex polydrug implants. However, the multi-factorial nature of the inkjet printing process makes formulation (e.g., composition, surface tension, and viscosity) and printing parameter optimization (e.g., nozzle diameter, peak voltage, and drop spacing) an empirical and time-consuming endeavour. Instead, given the wealth of publicly available data on pharmaceutical inkjet printing, there is potential for a predictive model for inkjet printing outcomes to be developed. In this study, machine learning (ML) models (random forest, multilayer perceptron, and support vector machine) to predict printability and drug dose were developed using a dataset of 687 formulations, consolidated from in-house and literature-mined data on inkjet-printed formulations. The optimized ML models predicted the printability of formulations with an accuracy of 97.22%, and predicted the quality of the prints with an accuracy of 97.14%. This study demonstrates that ML models can feasibly provide predictive insights to inkjet printing outcomes prior to formulation preparation, affording resource- and time-savings.

Electrospun HPMC/PEO-blend orodispersible films: how slight batch differences affect the crucial mechanical properties

Orodispersible films comprise a promising dosage form with a wide range of advantages compared to conventional formulations. The electrospinning process can significantly enhance the relevant characteristics of orodispersible films, e.g., the dissolution rate and the ease of administration. This study involved the use of two types of hydroxypropyl methylcelluloses of low molecular weight obtained from three different manufacturers as the matrix. The SEM, FTIR, RAMAN, and DSC analyses revealed comparable values for all the fabricated materials. However, the mechanical properties of the fibers differed significantly, with electrospun Methocel E5/PEO proving to be particularly brittle. This is probably caused by the different arrangements of substituted methoxy- and hydroxypropyl groups of studied HPMCs. It is hoped that this paper will serve as an example of the extent to which slight differences between HPMC powder batches can dramatically alter the key properties of electrospun orodispersible films.

Development and Characterization of Pullulan-Based Orodispersible Films of Iron.

Iron deficiency is the principal cause of nutritional anemia and it constitutes a major health problem, especially during pregnancy. Despite the availability of various non-invasive traditional oral dosage forms such as tablets, capsules, and liquid preparations of iron, they are hard to consume for special populations such as pregnant women, pediatric, and geriatric patients with dysphagia and vomiting tendency. The objective of the present study was to develop and characterize pullulan-based iron-loaded orodispersible films (i-ODFs). Microparticles of iron were formulated by a microencapsulation technique, to mask the bitter taste of iron, and ODFs were fabricated by a modified solvent casting method. Morphological characteristics of the microparticles were identified by optical microscopy and the percentage of iron loading was evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES). The fabricated i-ODFs were evaluated for their morphology by scanning electron microscopy. Other parameters including thickness, folding endurance, tensile strength, weight variation, disintegration time, percentage moisture loss, surface pH, and in vivo animal safety were evaluated. Lastly, stability studies were carried out at a temperature of 25 °C/60% RH. The results of the study confirmed that pullulan-based i-ODFs had good physicochemical properties, excellent disintegration time, and optimal stability at specified storage conditions. Most importantly, the i-ODFs were free from irritation when administered to the tongue as confirmed by the hamster cheek pouch model and surface pH determination. Collectively, the present study suggests that the film-forming agent, pullulan, could be successfully employed on a lab scale to formulate orodispersible films of iron. In addition, i-ODFs can be processed easily on a large scale for commercial use.

Dual thermal stabilizing effects of xanthan gums via glycosylation and hydrogen bonding and in vivo human bioavailability of desmopressin in orodispersible film

Desmopressin acetate (DDAVP), a nonapeptide drug, is easily destroyed by heat in the manufacturing process of orodispersible film (ODF). A new challenging study was conducted to improve thermal stability through glycosylation and hydrogen bonding using carbohydrate gums (agar, arabic gum, carrageenan, xanthan gum) using the solvent casting method. Among gum types, xanthan gum strongly showed dual stabilizing effects of DDAVP via covalent glycosylation and hydrogen bonding, minimizing total impurities and optimizing physicochemical properties of ODF under accelerated conditions for six months. The optimized ODF formulation (O-DDAVP ODF) at a DDAVP and xanthan gum ratio of 1:1.5 had a pharmaceutically equivalent dissolution profile as compared with a commercial 0.2 mg commercial Minirin® tablet in four different media: pH 1.2, pH 4.0, and pH 6.8 buffers and deionized water. Furthermore, O-DDAVP ODF showed in vivo bioequivalence to Minirin® tablets in healthy human volunteers. Glycosylation-oriented stabilization of peptide drug using pharmaceutically active excipients against thermal denaturation could be challenged to design patient-friendly ODF.

Effect of the new 75-mg orodispersible film of sildenafil on erection and sexual quality of life: insights from an observational study.

The newly devised orodispersible film (ODF) of sildenafil is the first phosphodiesterase type 5 inhibitor (PDE5i) available in a 75-mg dose. This intermediate dose and the particular properties of the ODF formulation can improve the clinical management of erectile dysfunction (ED) patients. We investigated the effects of the sildenafil ODF 75-mg dose on both sexual quality of life and erectile function based on the results from an observational study in daily practice in Italy. This study was a post hoc analysis of results from an observational, real-life study carried out in ED patients at 6 treatment centers in Italy. All subjects were asked to take the prescribed dose of sildenafil ODF at inclusion (visit 1) and to return for a control visit (visit 2) to confirm or adapt the prescribed dose after a minimum of 4weeks. An end of study control visit (visit 3) was performed after additional 4weeks. Erectile function, assessed by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain; sexual quality of life, measured using the sexual quality of life instrument for men (SQoL-M). Among the 36 subjects initially recruited for the 75-mg dose, 5 patients dropped out of the study (2 at visit 2 and 3 at visit 3), none of whom due to treatment inefficacy or serious adverse events. At visit 2, the mean (SD) IIEF-EF scores significantly increased (∆ = 7.97[4.71], P < 0.0001) as SQoL-M scores also did (∆ = 10.76[10.46], P < 0.0001). At visit 3, IIEF-EF and SQoL-M scores were still significantly improved compared to baseline (∆ = 10.64[7.01], P < 0.0001, and ∆ = 18.15[12.32], P < 0.0001, respectively). By ANCOVA, we found no significant effects for age, BMI, previous use of PDE5i, presence of metabolic comorbidities, or smoking habits on study outcomes at both visits 2 and 3. The new 75-mg ODF sildenafil formulation is a safe and effective treatment for ED, significantly improving both erectile function and sexual quality of life in patients undergoing treatment. This is the first study assessing the efficacy of the sildenafil ODF 75-mg dose in a real-life setting. However, the small sample size, possible underlying cultural factors, and limited availability of clinically relevant data may have affected the reliability of our results. The use of the 75 mg ODF formulation for sildenafil represents an effective and safe novel treatment option for ED patients.

Development of 3D Printed Multi-Layered Orodispersible Films with Porous Structure Applicable as a Substrate for Inkjet Printing.

The direct tailoring of the size, composition, or number of layers belongs to the advantages of 3D printing employment in producing orodispersible films (ODFs) compared to the frequently utilized solvent casting method. This study aimed to produce porous ODFs as a substrate for medicated ink deposited by a 2D printer. The innovative semi-solid extrusion 3D printing method was employed to produce multilayered ODFs, where the bottom layer assures the mechanical properties. In contrast, the top layer provides a porous structure for ink entrapment. Hydroxypropyl methylcellulose and polyvinyl alcohol were utilized as film-forming polymers, glycerol as a plasticizer, and sodium starch glycolate as a disintegrant in the bottom matrix. Several porogen agents (Aeroperl® 300, Fujisil®, Syloid® 244 FP, Syloid® XDP 3050, Neusilin® S2, Neusilin® US2, and Neusilin® UFL2) acted as porosity enhancers in the two types of top layer. ODFs with satisfactory disintegration time were prepared. The correlation between the porogen content and the mechanical properties was proved. A porous ODF structure was detected in most samples and linked to the porogen content. SSE 3D printing represents a promising preparation method for the production of porous ODFs as substrates for subsequent drug deposition by 2D printing, avoiding the difficulties arising in casting or printing medicated ODFs directly.

Formulation and Characterization of Montelukast Sodium Mouth Dissolving Film Using Cress Seed Mucilage

There is a rising interest in the development of orodispersible films (ODFs) as an alternative to fast dissolving tablets which is attributed to their faster dissolution rate, higher durability, and better patient compliance. Owing to its rheological and also various functional properties, many researchers tried to discover some of the pharmaceutical applications of L. sativum in the development of various dosage forms, in addition to its therapeutic studies, such as binding, dissolving, gelling and sustained release dosage form. The fast-dissolving oral film of the Montelukast sodium by using Cress seed mucilage (CSM) and HPMC (15cps) is prepared by solvent casting method. The fast-dissolving oral film evaluated for folding endurance, surface pH, in-vitro disintegration time, drug content and in-vitro drug release. The physical appearance and folding endurance properties were found to be reasonably good and electron microscopy shows that films are clear, colorless with smooth surface.The drug content of all the films was in the range suggesting that drug was uniformly dispersed throughout all films. The present study was an attempt to develop and evaluate an oral fast dissolving drug delivery system using cress seed mucilage as a film former.&#x0D; Keywords: Orodispersible film, Montelukast sodium, Cress seed mucilage, HPMC

Orodispersible Films-Current State of the Art, Limitations, Advances and Future Perspectives.

Orodispersible Films (ODFs) are drug delivery systems manufactured with a wide range of methods on a big scale or for customized medicines and small-scale pharmacy. Both ODFs and their fabrication methods have certain limitations. Many pharmaceutical companies and academic research centers across the world cooperate in order to cope with these issues and also to find new formulations for a wide array of APIs what could make their work profitable for them and beneficial for patients as well. The number of pending patent applications and granted patents with their innovative approaches makes the progress in the manufacturing of ODFs unquestionable. The number of commercially available ODFs is still growing. However, some of them were discontinued and are no longer available on the markets. This review aims to summarize currently marketed ODFs and those withdrawn from sale and also provides an insight into recently published studies concerning orodispersible films, emphasizing of utilized APIs. The work also highlights the attempts of scientific communities to overcome ODF's manufacturing methods limitations.

Mechanical, optical, and physicochemical properties of HPMC-based doxazosin mesylate orodispersible films

In this study, orodispersible films formed from hydroxypropyl methylcellulose (HPMC) E6 (2, 2.5, and 3%) and plasticizers ((glycerin (Gly), propylene glycol (PP), or polyethylene glycol (PEG)), containing doxazosin mesylate, were prepared by the solvent casting method and characterized. Design of experiments (DoE) was used as a statistical tool to facilitate the interpretation of the experimental data and allow the identification of optimal levels of factors for maximum formulation performance. Differential scanning calorimetry (DSC) curves and X-ray powder diffraction (XRPD) diffractograms showed doxazosin mesylate amorphization, probably due to complexation with the polymer (HPMC E6), and the glass transition temperature of the polymer was reduced by adding a plasticizer. Fourier transformed infrared (FTIR) spectroscopy results showed that the chemical structure of doxazosin mesylate was preserved when introduced into the polymer matrix, and the plasticizers, glycerin and PEG, affected the polymer matrix with high intensity. The addition of plasticizers increased the elongation at break and adhesiveness (Gly > PEG > PP), confirming the greater plasticizer effect of Gly observed in DSC and FTIR studies. Greater transparency was observed for the orodispersible films prepared using PP. The addition of citric acid as a pH modifier was fundamental for the release of doxazosin mesylate, and the desirability formulation had a release profile similar to that of the reference product.

Preparation and properties characterization of composite modified starch-based orodispersible films

Preparation and properties characterization of composite modified starch-based orodispersible films

Starch-based orodispersible film for diclofenac release

Starch-based orodispersible film for diclofenac release

Bioequivalence Studies of Sildenafil Citrate Orodispersible Film Administered with and without Water vs ViagraⓇ Film-Coated Tablets in Healthy Male Volunteers

Bioequivalence Studies of Sildenafil Citrate Orodispersible Film Administered with and without Water vs ViagraⓇ Film-Coated Tablets in Healthy Male Volunteers

Embedding of Poorly Water-Soluble Drugs in Orodispersible Films-Comparison of Five Formulation Strategies.

The poor bioavailability of many newly developed active pharmaceutical ingredients (APIs) poses a major challenge in formulation development. To overcome this issue, strategies such as the preparation of amorphous solid dispersions (ASDs), and the application of the APIs in lipid nanocarriers or the wet-milling of the substances into nanoparticles have been introduced. In addition to an efficient formulation strategy, a dosage form that is accepted by all patients is also of great importance. To enable a simple application of the oral dosage form for all patients, orodispersible films (ODFs) are a very promising delivery platform for the APIs because the films directly disintegrate in the mouth. In this study, two poorly water-soluble APIs, fenofibrate and naproxen, were formulated using five different formulation strategies and then embedded in ODFs. It was found that the deliverable amount of API with one ODF highly depends on the formulation strategy as well as the physicochemical properties of the formulated API. The most promising film formulations were ASD-ODFs as well as films with API-loaded lipid nanoemulsions. Both showed a reduction of the dissolution time of the APIs from the ODF compared to an ODF with unformulated API micro particles. In addition, short disintegration times were achieved, although the mechanical film properties were slightly worse compared to the API-free film formulation.