Orodispersible Film Formulation Research Articles

Nanoemulsion-Based Orodispersible Film Formulation of Guava Leaf Oil for Inhibition of Oral Cancer Cells.

Among natural sources, guava leaf oil (GLO) has emerged as a potential anticancer agent. However, its limited water solubility poses a significant challenge for its use. Oil-in-water nanoemulsions are used to address the limitation of water solubility of GLO prior to its incorporation into orodipersible films. Nanoemulsions containing GLO:virgin coconut oil (VCO) at a ratio of 50:50 to 70:30 presented a small droplet size of approximately 50 nm and a relatively low zeta potential. GLO:VCO at a ratio of 70:30 was selected for incorporation into sodium alginate film at various concentrations ranging from 1% to 30% w/w. Tensile strength and elongation at break relied on the concentration of nanoemulsions as well as the internal structure of films. Fourier transform infrared spectroscopy revealed that GLO was compatible with sodium alginate. Film containing 2% w/w of nanoemulsions (2G_ODF) exhibited effective in vitro antioral cancer activity, with an IC50 of 62.49 ± 6.22 mg/mL; furthermore, its anticancer activity showed no significant difference after storage at 25 °C for 1 year. Moreover, 2G_ODF at IC60 arrested colony formation and cell invasion. There is also evidence that cell death occurred via apoptosis, as indicated by nuclear fragmentation and positive Annexin-V staining. These findings highlight the potential of orodispersible films containing GLO nanoemulsions as a prospective oral anticancer agent.

REVIEW PENGARUH PENGGUNAAN SURFAKTAN PADA KARAKTERISTIK SEDIAAN ORODISPERSIBLE FILM (ODF) OBAT BERKELARUTAN RENDAH DALAM AIR: SIFAT DISINTEGRASI DAN DISOLUSI

Orodispersible film (ODF) is a drug delivery gaining widespread acceptance because it disintegrates quickly and can be self-administered. ODF has the advantage of increasing the active pharmaceutical ingredient (API) effectiveness by rapid dissolution in the oral cavity after direct contact with saliva. One of the components of ODF that influences the physical characteristics and dissolution of low-soluble drugs in water is surfactant. This material acts as a wetting or dispersing agent so the film can quickly disintegrate and release API. The method used is searching for international journal data using the Google Scholar. The surfactants reported to have been used in the ODF formulation are L-arginine, poloxamer 407, tween 80, and sodium dodecyl sulfate. In general, surfactant usage significantly affects the disintegration behavior of the film and API release. This behavior is caused by reducing the interfacial tension between phases by surfactants, which causes increased solid surface wetting and helps speed up the film disintegration and API dissolution from the ODF matrix. The conclusion is that surfactant usage with the appropriate type and concentration will help improve the ODF quality, especially in the disintegration properties of the dosage form and API dissolution.

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.

Orodispersible films based on jambolan juice and natural extracts: Development, characterization and sensory evaluation

AbstractBackgroundThe orodispersible films (ODFs) are ultra‐thin films that dissolve rapidly within the oral cavity. These can be used to carry vitamins, nutraceutical compounds and drugs. Generally, its formulated with synthetic polymers and artificial colorants. Due to growing consumer interest in healthier products, it is necessary to study the use of natural materials for ODF production, such as fruit juices and natural extracts. In this study, ODFs were prepared using pectin, jambolan juice and extracts of guaco, pomegranate, clove or cinnamon in different concentrations. The impact of the addition of natural extracts in different concentrations was evaluated by the following properties of the films: swelling, disintegration time, tensile strength, elongation at break, Young's modulus, work of adhesion, visual and sensory.ResultsThe films showed a visually homogeneous purple color, slowly disintegrating (from 1.1 ± 0.1 to 2.2 ± 0.1 min), flexible, and adherent enough independently of the extract used. The anthocyanin present in the jambolan juice (6.58 ± 0.02 mg g−1) contributed higher antioxidant capacity shown by the ODF (198–292 μMol TEg−1). The sensory evaluation reveals that the films presented adequate acceptance for a new kind of product.ConclusionThe results indicate the use of jambolan juice and natural extracts is suitable for the formulation of ODFs as a healthy product, maintaining technological properties.

Orodispersible thin films: A Hodiernal Perspective in Drug Delivery System

Undoubtedly that the ongoing epoch of pharmaceutical research has been focusing on the productive technological evolution of the drug delivery system so that the effectiveness appropriate to drug and patient’s sustainability can be strengthened. As determination and generation of present day chemical agents or substances are complex, expensive, and time-consuming procedure, so neoteric trends are reposition towards the drafting and advancing the inventive drug delivery systems for existing drugs. Among various pharmaceutical forms, orodispersible thin films have gained more interest from drug formulators to develop rapid drug-releasing formulations, especially for pediatrics and geriatrics patients. Furthermore, these strips have diverse merits over traditional fast-moving disintegrating tablets in consideration of schizophrenic and dysphasia patients. This convenience accommodates both the supremacy of marketing and enlarges patient compliance with this oral dosage form. Solvent casting and semi-solid casting methods are primary techniques that are used for the formulation of orodispersible thin films using a wide variety of hydrophilic polymers to achieve the desired biopharmaceutical attributes. In the current analysis article, recent improvements in the formulations of orodispersible films with their regulatory perspective are compiled.

Development and Evaluation of Fluoxetine Fast Dissolving Films: An Alternative for Noncompliance in Pediatric Patients

The most used pharmaceutical formulations for children are syrups, suppositories, soft chewable capsules, and mini-tablets. Administrating them might create an administration discomfort. This study aimed to develop and evaluate orodispersible films (ODFs) for pediatric patients in which the fluoxetine (FX) is formulated in the polymeric matrix. Six FX fast dissolving films (10 mg FX/ODF), FX1, FX2, FX3, FX4, FX5, and FX6, were prepared by solvent casting technique. In the composition of the ODFs, the concentration of the hydroxypropyl methylcellulose and the concentration of the propylene glycol were varied. Each formulation of fluoxetine ODF was evaluated by determining the tensile strength, folding endurance, disintegration, behavior in the controlled humidity and temperature conditions, and adhesiveness. All the obtained results were compared with the results obtained for six ODFs prepared without FX. The disintegration time of the FX ODFs was of maximum 88 s for FX2. Via the in vitro releasing study of the FX from the ODFs it was noticed that FX1 and FX2 allow a better release of the drug 99.98 ± 3.81% and 97.67 ± 3.85% being released within 15 min. From the obtained results it was also confirmed that FX ODFs were found to follow first-order release kinetic.

Optimal Design, Characterization and Preliminary Safety Evaluation of an Edible Orodispersible Formulation for Pediatric Tuberculosis Pharmacotherapy.

The severity of tuberculosis (TB) in children is considered a global crisis compounded by the scarcity of pharmaceutical formulations suitable for pediatric use. The purpose of this study was to optimally develop and evaluate a pyrazinamide containing edible orodispersible film formulation potentially suitable for use in pediatrics actively infected with TB. The formulation was prepared employing aqueous-particulate blending and solvent casting methods facilitated by a high performance Box Behnken experimental design template. The optimized orodispersible formulation was mechanically robust, flexible, easy to handle, exhibited rapid disintegration with initial matrix collapse occurring under 60 s (0.58 ± 0.05 min ≡ 34.98 ± 3.00 s) and pyrazinamide release was controlled by anomalous diffusion coupled with matrix disintegration and erosion mechanisms. It was microporous in nature, light weight (57.5 ± 0.5 mg) with an average diameter of 10.5 mm and uniformly distributed pyrazinamide load of 101.13 ± 2.03 %w/w. The formulation was physicochemically stable with no evidence of destructive drug–excipient interactions founded on outcomes of characterization and environmental stability investigations. Preliminary inquiries revealed that the orodispersible formulation was cytobiocompatible, palatable and remained intact under specific storage conditions. Summarily, an edible pyrazinamide containing orodispersible film formulation was optimally designed to potentially improve TB pharmacotherapy in children, particularly the under 5 year olds.

A Pediatrics Utilization Study in The Netherlands to Identify Active Pharmaceutical Ingredients Suitable for Inkjet Printing on Orodispersible Films.

Background: The use of medication in pediatrics, children aged 0–5 years, was explored so as to identify active pharmaceutical ingredients (APIs) suitable for inkjet printing on a plain orodispersible film (ODF) formulation in a pharmacy. Methods: The database IADB.nl, containing pharmacy dispensing data from community pharmacies in the Netherlands, was used to explore medication use in the age group of 0–5 years old, based on the Anatomical Therapeutic Chemical classification code (ATC code). Subsequently, a stepwise approach with four exclusion steps was used to identify the drug candidates for ODF formulation development. Results: there were 612 Active Pharmaceutical Ingredients (APIs) that were dispensed to the target group, mostly antibiotics. Of the APIs, 221 were not registered for pediatrics, but were used off-label. After the exclusion steps, 34 APIs were examined regarding their suitability for inkjet printing. Almost all of the APIs were sparingly water soluble to practically insoluble. Conclusion: Pharmaceutical inkjet printing is a suitable new technique for ODF manufacturing for pediatric application, however the maximal printed dose as found in the literature remained low. From the selected candidates, only montelukast shows a sufficiently high water-solubility to prepare a water-based solution. To achieve higher drug loads per ODF is ambitious, but is theoretically possible by printing multiple layers, using highly water-soluble APIs or highly loaded suspensions.

Orodispersible films as a personalized dosage form for nursing home residents, an exploratory study

Background A frequent problem in ageing patients, and thus in nursing home residents, is dysphagia, affecting the ability to swallow solid dosage forms. A promising and personalized drug delivery system for this patient group is the orodispersible film. Orodispersible films could be prepared extemporaneously in a (hospital) pharmacy setting or in specialty compounding community pharmacies using the solvent casting method. Little has been done to systematically investigate which medications should be chosen for orodispersible film formulation development. Objective In this study, the medication use of nursing home residents was examined to identify medications that are suitable for orodispersible film formulation development. Setting Nursing homes of three Northern provinces of Netherlands. Method Medication intake data from 427 nursing home residents from nine nursing homes from the three northern provinces of the Netherlands were used to identify candidates for orodispersible film formulation development. A stepwise approach, with exclusion steps, was used. Selection criteria included systemic use with a maximum amount of 100 mg per dose unit, no commercially available suitable dosage forms for administration in dysphagia, indication for diseases associated with dysphagia. Furthermore, the characteristics of the active pharmaceutical ingredient needed for the orodispersible film formulation development, such as water solubility and taste, were reviewed. Main outcome measure Active pharmaceutical ingredients suitable for orodispersible film formulation development. Results The nursing home residents used three hundred forty one different medications. Of those, 34 active pharmaceutical ingredients from six therapeutic groups were considered as candidates for orodispersible film formulation development. Most of these active pharmaceutical ingredients have a bitter taste and poor water solubility, which is a challenge for orodispersible film production. Conclusions The most suitable active pharmaceutical ingredient candidates for manufacturing of orodispersible films for the ageing patient population may be the combination of levodopa and carbidopa used to treat the symptoms of Parkinson’s disease, and baclofen used to treat spasticity.

Enhancement of Solubility of Lutein by Solid Dispersion Technique and Development of ITS STABLE Orodispersible Film Formulation

Enhancement of Solubility of Lutein by Solid Dispersion Technique and Development of ITS STABLE Orodispersible Film Formulation

Poly(methyl methacrylate) salt as film forming material to design orodispersible films

This work aims to evaluate the possible use of a poly(sodium methacrylate, methyl methacrylate) (NaPMM2) plasticized by PEG400 in the design of orodispersible films (ODF). Placebo ODF prepared by solvent casting were intended to study the impact of the polymer/plasticizer ratio and residual moisture on disintegration time, stickiness and mechanical properties. The drug loading capacity was assessed using ketoprofen and paracetamol. Placebo ODF containing PEG400 in the 10–30% w/w range and 10–15% of residual moisture content were easy-to-handle, packed without failures and completely dissolved within 30 s.NaPMM2/PEG400 in 80/20 ratio allowed up to 70% of paracetamol loading, which appeared as the largest value described in literature. This ODF showed good mechanical properties and disintegration time. The same formulation loaded with 25% or 50% ketoprofen (pKa = 4.45) swelled without disintegrating, because of a partial protonation of NaPMM2, as verified by ATR-FTIR spectroscopy. However, the addition of 5% surfactants allowed the formulation of ODF containing 25% ketoprofen that disintegrated within one minute and guaranteed the complete drug dissolution within 5 min. All the presented data, discussed in the framework of information available on such copolymer, highlighted its versatility in the design of orodispersible dosage forms.

Effectiveness and Safety of Oro-Dispersible Sildenafil in a New Film Formulation for the Treatment of Erectile Dysfunction: Comparison Between Sildenafil 100-mg Film-Coated Tablet and 75-mg Oro-Dispersible Film

BackgroundA new oro-dispersible film (ODF) formulation of sildenafil has been developed for the treatment of erectile dysfunction (ED) to overcome the drawbacks that some patients experience when taking the conventional film-coated tablet (FCT). AimTo assess the effectiveness and safety of sildenafil ODF formulation in patients with ED who were using the conventional FCT. MethodsFrom May 2017 through July 2017, 139 patients with ED were enrolled. Data from penile color-duplex ultrasound, medical history, hormonal evaluation, and patient self-administered questionnaires were collected. All patients were administered sildenafil 100-mg FCT for 4 weeks. Thereafter, they underwent a 2-week washout period and subsequently took sildenafil 75-mg ODF for 4 weeks. OutcomesThe International Index of Erectile Function (IIEF-15), Hospital Anxiety and Depression Scale (HADS), Patient Global Impressions of Improvement (PGI-I), and Clinician Global Impressions of Improvement (CGI-I) questionnaires were administered and severity of ED was classified as severe (IIEF-15 score ≤ 10), moderate (IIEF-15 score 11–16), or mild (IIEF-15 score = 17–25). ResultsAll patients completed the final protocol. Differences in mean IIEF scores for erectile function, orgasmic function, sexual desire, and intercourse satisfaction were significantly in favor of sildenafil 100-mg FCT, whereas the mean score for overall satisfaction was in favor of sildenafil 75-mg ODF. A significant difference in changes in HADS score was found from washout to final follow-up (mean difference = −0.19; P < .01). For the ODF formulation, the median CGI-I score was 3.5 (interquartile range [IQR] = 2.5–4.5) and the median PGI-I score was 3.0 (IQR = 2.0–4.0). The median action time was 20.0 minutes (IQR = 15.0–30.0) and the median mouth time was 60.0 seconds (IQR = 30.0–120.0). Clinical ImplicationsThe ODF formulation of a widely known drug, with the same safety and effectiveness of the FCT, was better appreciated by patients in overall satisfaction. Strengths and LimitationsThis is the first clinical trial to assess the efficacy of a new formulation of sildenafil in patients with ED. The limitations of the study are related to the methodology used: it was not a case-control study and the patients were not drug-naïve for ED treatment. Therefore, only the “additional” side effects of the ODF formulation compared with FCT are reported. ConclusionThe new ODF formulation is as efficient and safe as the FCT formulation and offers a new choice of treatment to specialists for more precisely tailored therapy.Cocci A, Capece M, Cito G, et al. Effectiveness and Safety of Oro-Dispersible Sildenafil in a New Film Formulation for the Treatment of Erectile Dysfunction: Comparison Between Sildenafil 100-mg Film-Coated Tablet and 75-mg Oro-Dispersible Film. J Sex Med 2017;14:1606–1611.

Formulation of orodispersible films for paediatric therapy: investigation of feasibility and stability for tetrabenazine as drug model.

Orodispersible films (ODF) were formulated to facilitate tetrabenazine (TBZ) administration to paediatric population for the treatment of hyperkinetic movement disorders. ODF were obtained by solvent casting/evaporation method using four different polymers (HPMC, PVP, pullulan and HEC). Physicochemical, mechanical and biopharmaceutical characterizations as well as API state in ODF by thermal analysis were investigated to define and compare formulations. ODF stability was also monitored during 6 months to follow evolution of properties. Analyses at T0 showed few differences between formulations: results of physicochemical and mechanical characterizations were almost similar for each formulation and TBZ appeared at the amorphous state in all cases. ODF delivery system allowed a major improvement of TBZ dissolution profile in buccal conditions compared with pure drug. However, after 3 and 6 months of stability, a TBZ recrystallization occurred for formulations based on PVP and HEC associated with a decrease of drug release in saliva conditions. HPMC-ODF (F1) appeared as the best formulation. Indeed, physicochemical, mechanical and biopharmaceutical characteristic remained intact. In addition, TBZ remained in amorphous state during stability study.

Fabrication and Evaluation of Fast Disintegrating Oral Hybrid Films of Propranolol Hydrochloride by Using Pectin and Synthetic Polymers

The main aim of this investigation is to develop fast disintegrating oral films of Propranolol hydrochloride by using Pectin and synthetic polymers. The Propranolol HCl oro-dispersible films were formulated by using HPMC E15LV, HPMC regular, pectin, Carbopol, and PVA, as film forming polymers. The selected polymers were natural and synthetic water soluble polymers. Generally solvent casting method was used in the manufacture of the mouth dissolving films. The formula which incorporates pectin HPMC E15 LV 4:2 and pectin: Carbopol 3:2 ratios and also other varying ratio were used in the formulation of Oro-dispersible films. The quantity and type of plasticizer affected the formulation of films; Propranolol HCl has bitter taste so taste masking agents were used. Citric acid was used as a salivary stimulating agent. The prepared films were subjected to the analysis of various evaluation tests such as weight variation, tensile strength, thickness, surface pH, and drug content. The significant parameters such as disintegration and dissolution profiles also studied in detail since the product was prepared for fast dissolving in the oral cavity.

Preparation and Characterization of Ultrarapidly Dissolving Orodispersible Films for Treating and Preventing Iodine Deficiency in the Pediatric Population.

Iodine deficiency is a public health problem that is easily prevented in many countries through having a salt iodization program. However, the World Health Organization (WHO) recommends that particular population groups including infants and young children have a sufficient level of daily iodine intake, while also reducing salt consumption in their diet. While many iodine supplements are available, swallowing tablet supplements is physically difficult for young children; thus, there is a need for the development of novel iodine delivery systems for pediatric patients. In this study a novel, ultrarapidly dissolving, nanofiber-based orodispersible film formulation containing iodine which is constructed from nanofibers was manufactured using an electrospinning technique. The potassium iodate (KIO3)-loaded poly(ethylene oxide) (PEO) fiber orodispersible films dissolve within seconds on wetting (applying on the tongue) without the need for the consumption of water. The electrospinning process and KIO3 loading did not alter the crystallinity and conformation of PEO. With high loading, KIO3 nanocrystals are present in the fibers. This formulation design allows easy administration of iodine for preventing childhood iodine deficiency. We have also described a novel and easy method for producing and harvesting nanocrystals of inorganic salts that can be potentially adopted for use in other relevant fields.

Effect of type and ratio of solubilising polymer on characteristics of hot-melt extruded orodispersible films

In formulating an orodispersible film (ODF), it is important for polymer choice to strike a balance between mechanical properties and release rates. Studies have been done to study polymer combinations. However, there is a lack of a systematic study to determine key factors affecting these properties. We studied the effect of varying the ratios of a solubilising polymer (Kollidon(®) VA 64 or Soluplus(®)) to a film forming polymer, hydroxypropyl cellulose (HPC), on mechanical properties and release rates of hot-melt extruded ODFs using a 2(3) factorial design. The two drugs evaluated were chlorpheniramine and indomethacin. The main effects impacting mechanical properties were the drug and two-way interaction between drug and solubilising polymer. For dissolution, the main effects were the solubilising polymer; the drug; and the two-way interaction between solubilising polymer and ratio of solubilising to film forming polymer. Both drugs exhibited plasticising effects on the polymer matrix and had higher film ductility and lower film stiffness. Kollidon(®) VA 64-containing films performed better in terms of drug release whereas Soluplus(®)-containing films had better mechanical properties. The dissolution rate can be improved by decreasing film thickness. The findings of our study will be crucial to forming a robust ODF formulation.

Characterization and Optimization of Orodispersible Mosapride Film Formulations

Orodispersible film (ODF) technology offers new possibilities for drug delivery by providing the advantages of oral delivery coupled with the enhanced onset of action and convenience to special patient categories such as pediatrics and geriatrics. In this study, mosapride (MOS) was formulated in an ODF preparation that can be used for treatment of patients who suffer from gastrointestinal disorders, especially difficulty in swallowing due to gastroesophageal reflux disease. Poloxamer 188 was used to solubilize MOS to allow its incorporation into the film matrix. The films were prepared by solvent-casting method using different polymer ratios of maltodextrin and hydroxypropyl methylcellulose and plasticizer levels of glycerol and propylene glycol. A D-optimal design was utilized to study the effect of polymer ratio, plasticizer type, and level on film mechanical properties, disintegration time, and dissolution rate. Statistical analysis of the experimental design showed that the increase of maltodextrin fraction and plasticizer level conferred optimum attributes to the prepared films in terms of film elasticity, film disintegration time, and MOS release rate. The ODF formulations were further tested for moisture sorption capacity, with formulations containing a higher ratio of maltodextrin and percent plasticizer showing more moisture uptake. The optimum film composition was also tested in vivo for film palatability and disintegration time. An optimized mosapride orodispersible film formulation was achieved that could be of benefit to patients suffering from gastrointestinal disorders.