Fast-dissolving Films Research Articles

Development and Evaluation of Fast Dissolving Film for Oro-Buccal Drug Delivery of Chlorpromazine

Abstract: Objective: Objective was designed to prepare, develop and evaluate fast dissolving films (FDFs) for oro-buccal drug delivery of chlorpromazine. Background: The drug delivery through oro-buccal mucosa is very interesting one but it partially lacked oro-buccal delivery products in the market. Methods: FDFs of chlorpromazine were prepared by solvent casting method using polymers PVA, HPMCE-5, HPMCE-15 and were evaluated for film specific parameters. FDFs were also evaluated for dissolution and percentage drug release by in vitro and ex vivo dissolution or drug permeation study. Results: The prepared films DPF1, DHF2, DHF3, DHPF4 and DHPF5 were of smooth surface without bubbles and cracks; flexible and non-sticky; uniform in weight without any significant weight variation; around to neutral surface pH; unchanged folding endurance; 84-95 %mg drug content variation. Thickness of DPF1 was less compared to DHF2, DHF3, DHPF4 and DHPF5. DPF1 showed excellent elasticity and undergone disintegration in less time. Chlorpromazine was rapidly released in vitro from all formulations and release was found to be maximum 97.2% over a period of 150s in DPF1. Chlorpromazine was significantly more rapidly released ex vivo from DPF1 and release was found to be 85.10% over a period of 150s. Conclusion: The prepared FDFs of chlorpromazine were in accordance to the standard range of film specific parameters and comply it. FDF of chlorpromazine prepared with the polymer PVA is better than other prepared films with other polymers for oro-buccal drug delivery of chlorpromazine in buccal cavity for the treatment of either psychosis or emesis. Key words: Chlorpromazine, Fast dissolving film, Oro-buccal drug delivery, in vitro, ex vivo.

FORMULATION AND EVALUATION OF ORAL FAST DISSOLVING FILMS OF MELOXICAM

FORMULATION AND EVALUATION OF ORAL FAST DISSOLVING FILMS OF MELOXICAM

Formulation and Evaluation of Orally Fast Dissolving Wafer by Using Natural Gum: Review Article

Oral thin film a new drug delivery system for the oral delivery of the drugs, was developed based on the technology of the transdermal patch. Fast-dissolving oral thin film is a solid dosage form, which disintegrate or dissolve within 1 min when placed in the mouth without drinking water or chewing. Oral film includes various ingredients for its formulation. Fast dissolving film is prepared using hydrophilic polymers that rapidly dissolves on the tongue or buccal cavity, delivering the drugto the systemic circulation via dissolution when contact with liquid is made. Water-soluble polymers are used as film formers for fast dissolving films. The water-soluble polymers achieve rapid disintegration, good mouth feel and mechanical properties to the films. Fast-dissolving oral thin film offer fast, accurate dosing in a safe, efficacious format that is convenient and portable, without the need for water or measuring devices

Oral fast-dissolving films containing lutein nanocrystals for improved bioavailability: formulation development, in vitro and in vivo evaluation

Lutein is widely used as diet supplement for prevention of age-related macular degeneration. However, the application and efficacy of lutein in food and nutritional products has been hampered due to its poor solubility and low oral bioavailability. This study aimed to develop and evaluate the formulation of oral fast-dissolving film (OFDF) containing lutein nanocrystals for enhanced bioavailability and compliance. Lutein nanocrystals were prepared by anti-solvent precipitation method and then encapsulated into the films by solvent casting method. The formulation of OFDF was optimized by Box-Behnken Design (BBD) as follows: HPMC 2.05% (w/v), PEG 400 1.03% (w/v), Cremophor EL 0.43% (w/v). The obtained films exhibited uniform thickness of 35.64±1.64μm and drug content of 0.230±0.003mg/cm2 and disintegrated rapidly in 29±8s. The nanocrystal-loaded films with reconstituted particle size of 377.9nm showed better folding endurance and faster release rate in vitro than the conventional OFDFs with raw lutein. The microscope images, thermograms, and diffractograms indicated that lutein nanocrystals were highly dispersed into the films. After administrated to SD rats, t max was decreased from 3h for oral solution formulation to less than 0.8h for OFDF formulations, and C max increased from 150ng/mL for solution to 350ng/mL for conventional OFDF or 830ng/mL for nanocrystal OFDF. The AUC 0-24h of conventional or nanocrystal OFDF was 1.37 or 2.08-fold higher than that of the oral solution, respectively. These results suggested that drug nanocrystal-loaded OFDF can be applied as a promising approach for enhanced bioavailability of poor soluble drugs like lutein.

FORMULATION AND EVALUATION OF FAST DISSOLVING ORAL FILMS OF PROCHLORPERAZINE MALEATE

The objective of the present study was to prepare and evaluate fast-dissolving oral films of prochlorperazine maleate (PCM), in order to enhance the bioavailability of the drug and to provide rapid onset of action thereby improving patient compliance. The solubility of the drug was increased by preparing inclusion complex with 2-hydroxypropyl-β-cyclodextrin (2HPβCD) and then incorporating it into the fast dissolving films. The fast-dissolving films of PCM were prepared by solvent casting method using different film forming polymers such as HPMC E15 and HPMC E5, either as single polymer or combination of the two. The film formulations were evaluated for various physico-chemical parameters. All formulations released more than 85% of the drug within 15 minutes. Formulation F4 showed best in vitro drug release profile. From the ex vivo study it was found that 94.79% of drug permeated through the porcine oral mucosa from the optimized formulation F4 within 60 mins.

Preparation and characterization of fast dissolving pullulan films containing BCS class II drug nanoparticles for bioavailability enhancement

The aim of this study is to assess pullulan as a novel steric stabilizer during the wet-stirred media milling (WSMM) of griseofulvin, a model poorly water-soluble drug, and as a film-former in the preparation of strip films via casting–drying the wet-milled drug suspensions for dissolution and bioavailability enhancement. To this end, pullulan films, with xanthan gum (XG) as thickening agent and glycerin as plasticizer, were loaded with griseofulvin nanoparticles prepared by WSMM using pullulan in combination with sodium dodecyl sulfate (SDS) as an ionic stabilizer. The effects of drug loading and milling time on the particle size and suspension stability were investigated, as well as XG concentration and casting thickness on film properties and dissolution rate. The nanosuspensions prepared with pullulan–SDS combination were relatively stable over 7 days; hence, this combination was used for the film preparation. All pullulan-based strip films exhibited excellent content uniformity (most <3% RSD) despite containing only 0.3–1.3 mg drug, which was ensured by the use of precursor suspensions with >5000 cP viscosity. USP IV dissolution tests revealed fast/immediate drug release (t80 < 30 min) from films <120 μm thick. Thinner films, films with lower XG loading, or smaller drug particles led to faster drug dissolution, while drug loading had no discernible effect. Overall, these results suggest that pullulan may serve as an acceptable stabilizer for media milling in combination with surfactant as well as a fast-dissolving film former for the fast release of poorly water-soluble drug nanoparticles.

Development of polymer-bound fast-dissolving metformin buccal film with disintegrants.

Fast-dissolving drug-delivery systems are considered advantageous over the existing conventional oral dosage forms like tablets, capsules, and syrups for being patient friendly. Buccal films are one such system responsible for systemic drug delivery at the desired site of action by avoiding hepatic first-pass metabolism. Metformin hydrochloride (Met), an antidiabetic drug, has poor bioavailability due to its high solubility and low permeability. The purpose of the study reported here was to develop a polymer-bound fast-dissolving buccal film of metformin to exploit these unique properties. In the study, metformin fast-dissolving films were prepared by the solvent-casting method using chitosan, a bioadhesive polymer. Further, starch, sodium starch glycolate, and microcrystalline cellulose were the disintegrants added to different ratios, forming various formulations (F1 to F7). The buccal films were evaluated for various parameters like weight variation, thickness, folding endurance, surface pH, content uniformity, tensile strength, and percentage of elongation. The films were also subjected to in vitro dissolution study, and the disintegration time was found to be less than 30 minutes for all formulations, which was attributed to the effect of disintegrants. Formulation F6 showed 92.2% drug release within 6 minutes due to the combined effect of sodium starch glycolate and microcrystalline cellulose.

Fast-Dissolving Films of Sumatriptan Succinate: Factorial Design to Optimize In Vitro Dispersion Time

Sumatriptan succinate, a serotonin 5-HT agonist, commonly used for migraine has erratic absorption from the gastrointestinal tract following oral administration and undergoes first-pass metabolism, resulting in a low bioavailability. The present study was undertaken to formulate fast-dissolving films of sumatriptan succinate meant to be quickly dispersed in the mouth. Films were prepared by solvent casting method and characterized for thickness, folding endurance, elongation, surface pH, and content uniformity. A 32 factorial design was used to optimize the in vitro dispersion time of films, and in vitro dissolution study was studied to determine the drug release. Ex vivo buccal permeation study was carried out using goat buccal mucosa mounted on a modified Franz diffusion cell. The optimized in vitro dispersion time for both the type of films was ∼30 s. The in vitro drug dissolution was complete in 90 s for both types of films. Thirty-eight percent of the drug was permeated from the hydroxy propyl methyl cellulose (HPMC) film, and about 42 % was permeated from maltodextrin film in 30 min. Such fast-dissolving films of sumatriptan succinate would mediate the release of drug and would be potentially useful for the treatment of migraine where quick onset of action is required.

Formulation and evaluation of fast-dissolving films of lisinopril

Objective The aim of this study was to formulate and evaluate the oral fast-dissolving film of lisinopril for the effective management of hypertension and cardiac diseases. Materials and methods Fast-dissolving films were prepared by the solvent-casting method using a combination of different polymers, HPMC E5 LV, HPMC E 3 and HPMC 4KM, along with PEG as a plasticizer. The Fourier-transform infrared study for the drug-polymer interaction was carried out. Evaluation of physical parameters such as physical appearance, surface texture, uniformity of weight, uniformity of strip thickness, surface pH, folding endurance, uniformity of drug content and percentage of moisture absorption were performed. Kinetic data analysis for the release study and the stability study were also performed. Result and conclusion Results of uniformity of weight, thickness, folding endurance, surface pH, tensile strength, percentage drug content, swelling index, tensile strength and percentage elongation of all the films were found to be satisfactory with respect to variation of these parameters between films of same formulation. The Fourier-transform infrared study indicated that there was no interaction between the drug and the polymers. The in-vitro drug release study showed that a better rate of drug release was achieved by formulations FA3, FB1, FB4 FC8 and FD10 compared with other formulations. The stability study did not show any significant difference in the external appearance, the drug content and the in-vitro drug release. The ex-vivo study indicated that the drug has a better ability to cross the sublingual barrier at a faster rate, and hence the delivery system was found to be promising as it has the potential of overcoming the drawbacks associated with tablet formulations available in the market presently.

Fast dissolving paracetamol/caffeine nanofibers prepared by electrospinning

A series of polyvinylpyrrolidone fibers loaded with paracetamol (PCM) and caffeine (CAF) was fabricated by electrospinning and explored as potential oral fast-dissolving films. The fibers take the form of uniform cylinders with smooth surfaces, and contain the drugs in the amorphous form. Drug–polymer intermolecular interactions were evidenced by infrared spectroscopy and molecular modeling. The properties of the fiber mats were found to be highly appropriate for the preparation of oral fast dissolving films: their thickness is around 120–130μm, and the pH after dissolution in deionized water lies in the range of 6.7–7.2. Except at the highest drug loading, the folding endurance of the fibers was found to be >20 times. A flavoring agent can easily be incorporated into the formulation. The fiber mats are all seen to disintegrate completely within 0.5s when added to simulated saliva solution. They release their drug cargo within around 150s in a dissolution test, and to undergo much more rapid dissolution than is seen for the pure drugs. The data reported herein clearly demonstrate that electrospun PCM/CAF fibers comprise excellent candidates for oral fast-dissolving films, which could be particularly useful for children and patients with swallowing difficulties.

Aminoacids as non-traditional plasticizers of maltodextrins fast-dissolving films

This study explored the effect of aminoacids as non-traditional plasticizers of maltodextrins fast dissolving films. 5% w/w glycine and proline decreased the glass transition temperature (Tg) of maltodextrins from 102.6±2.0°C to 73.1±1.4°C and 76.1±0.7°C, respectively; meanwhile the binary mixture made with lysine had a Tg value of 83.6±2.2°C. At the same time, all aminoacids increased the ΔCp values. The shift of the thermal data were due to profound effect on the hydrogen bonding as evidenced by ATR-FTIR spectra since the OH stretching and scissoring bands decreased of about 15–26cm−1. A linear relationship was found (R2=0.9334) between HOH scissoring wavenumbers and Tg values. The addition of glycine and proline resulted effective in reducing the elastic modulus (about 50%) and tensile strength (about three times) and, therefore, can be used to increase the film ductility.

Fast-dissolving ocular films of riboflavin acetate conjugate for treatment of keratoconus in UVA-CXL procedure: ex vivo permeation, hemolytic toxicity and apoptosis detection

Background: Attempts to facilitate corneal epithelial penetration of riboflavin (Rb) without de-epithelization, so far, include the use of penetration enhancers, to devitalize corneal epithelium in order to disturb tight epithelial interjunctional complexes and zonulae occludentes. Though such approaches result in sufficient epithelial permeability of Rb to guarantee efficacy of CXL procedure, they lack the evidences of safety. Prodrug with improved lipophilicity targeted toward esterases and amidases has proven to be an effective and promising approach to overcome lipophilic corneal epithelial barrier.Objectives: Fast-dissolving ocular films of newly synthesized and characterized riboflavin lipid conjugate (RbLDC) were developed to overcome corneal epithelial barrier resistance for treatment of keratoconus. The safety concern of the film was assessed by in vitro hemolytic toxicity and in vitro apoptosis detection for its safe clinical use.Results: The optimized film was tough, flexible and dissolved rapidly within 36.86 s in simulated tear fluid, pH 7.4. FE-SEM/EDX showed smooth surfaces of films and evidenced the quantitative elemental similarity, indicating drug homogeneity. The permeation profile of F18 demonstrated 13.28-fold increased permeation of RbLDC relative to Rb solution across intact cornea. Safety was confirmed by 3.74% hemolysis and 10% apoptosis.Conclusion: Safe and efficient RbLDC fast-dissolving ocular films capable of overcoming corneal epithelial barrier resistance to avoid surgical intervention of corneal epithelial debridement were developed.

Development of a vaginal delivery film containing EFdA, a novel anti-HIV nucleoside reverse transcriptase inhibitor

The aim of this work was to develop a fast-dissolving film formulation containing EFdA for potential use as a topical vaginal microbicide for prevention of HIV sexual transmission. Solid state compatibility approaches were used to screen commonly used polymers for formulation development. Factorial design and desirability function were used to investigate the effect of two variables, the ratio of the polymers and the concentration of selected plasticizer on four mechanical responses including tensile strength, elongation at break, toughness and elastic modulus for optimization of the film formulation. Assessments of EFdA-loaded films included physicochemical characteristics, in vitro cytotoxicity, epithelia integrity, ex vivo permeability and bioactivity test. The optimal placebo film was composed of PVA, HPMC E5 and propylene glycol (7:3:3, w/w), and its mechanical characteristics were comparable to those of VCF(®) film (a commercial vaginal film product). Permeability studies using human ectocervical explants showed that there was no significant difference in cumulative permeated amount of EFdA between EFdA film and free EFdA. The results of in vitro cytotoxicity and bioactivity testing showed that 50% cytotoxic concentration (CC50) was several orders of magnitude higher than 50% effective concentration (EC50) of EFdA. Furthermore, epithelial integrity study showed that EFdA-loaded film had a much lower toxicity to HEC-1A cell monolayers as compared to VCF(®). Therefore, EFdA-loaded vaginal film may be considered as a promising vaginal microbicide for HIV prevention.

“Real-time” disintegration analysis and D-optimal experimental design for the optimization of diclofenac sodium fast-dissolving films

The objective of this work was to study the dissolution and mechanical properties of fast-dissolving films prepared from a tertiary mixture of pullulan, polyvinylpyrrolidone and hypromellose. Disintegration studies were performed in real-time by probe spectroscopy to detect the onset of film disintegration. Tensile strength and elastic modulus of the films were measured by texture analysis. Disintegration time of the films ranged from 21 to 105 seconds whereas their mechanical properties ranged from approximately 2 to 49 MPa for tensile strength and 1 to 21 MPa% for young’s modulus. After generating polynomial models correlating the variables using a D-Optimal mixture design, an optimal formulation with desired responses was proposed by the statistical package. For validation, a new film formulation loaded with diclofenac sodium based on the optimized composition was prepared and tested for dissolution and tensile strength. Dissolution of the optimized film was found to commence almost immediately with 50% of the drug released within one minute. Tensile strength and young’s modulus of the film were 11.21 MPa and 6, 78 MPa%, respectively. Real-time spectroscopy in conjunction with statistical design were shown to be very efficient for the optimization and development of non-conventional intraoral delivery system such as fast dissolving films.

Development and Characterization of Pharmacokinetic Parameters of Fast Dissolving Films Containing Levocetirizine

A fast-dissolving film containing levocetirizine, a non-sedative antihistamine drug, was developed using pullulan, xanthan gum, propylene glycol, and tween 80 as the base materials. The drug content of the prepared films was within an acceptable limit as prescribed by the USP. The film exhibited excellent stability for four months when stored at 40 °C and 75% humidity. In vitro dissolution studies suggested a rapid disintegration, in which most of levocetirizine (93.54 ± 3.9%) dissolved within 90 seconds after insertion into the medium. Subsequently, Sprague–Dawley rats were used to compare the pharmacokinetic properties of the film preparation administered to the oral cavity, to those with oral administration of the pure drug solution. The pharmacokinetic parameters were similar between the two groups in which AUC0–t (ng h/ml), AUC0–∞ (ng h/ml) Cmax (ng/ml), Tmax (min), Kel (h−1), and t1/2 (h) of the reference were 452.033 ± 43.68, 465.78 ± 48.16, 237.16 ± 19.87, 30, 0.453 ± 0.051, and 1.536 ± 0.118, respectively, for the film formulation 447.233 ± 46.24, 458.22 ± 46.74, 233.32 ± 17.19, 30, 0.464 ± 0.060, and 1.496 ± 0.293, respectively. These results suggest that the present levocetirizine containing fast-dissolving film is likely to become one of the choices to treat different allergic conditions.

Formulation and evaluation of fast dissolving films of levocitirizine di hydrochloride

Introduction:Levocetirizine dihydrochloride is an orally active, third-generation non-sedative antihistamine used in the symptomatic relief of seasonal and perennial allergic rhinitis. The present work aimed at preparing quick release films of levocetirizine with the purpose of developing a dosage form for a very quick onset of action, which is beneficial in managing severe conditions of allergies, aiding in the enhancement of bioavailability, and is very convenient for administration, without the problem of swallowing and using water.Materials and Methods:The films of levocetirizine dihydrochloride were prepared by using polymers such as hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA), as either single polymer or in combination of two, by a solvent casting method. They were evaluated for physical characteristics such as uniformity of weight, thickness, folding endurance, drug content uniformity, surface pH, percentage elongation, and tensile strength, and gave satisfactory results. The formulations were subjected to disintegration, in vitro drug release tests, and in vivo studies on rats.Results:A marked increase in the dissolution rate was exhibited by fast-dissolving films of levocetirizine dihydrochloride containing HPMC as a polymer, when compared to conventional tablets. The haloperidol-induced catalepsy, milk-induced leukocytosis, and nasal provocation in vivo studies in rats proved that the fast-dissolving films of levocetirizine dihydrochloride produced a faster onset of action compared to the conventional tablets.Conclusions:Fast dissolving films of levocetirizine dihydrochloride can be considered suitable for clinical use in the treatment of allergic rhinitis and other conditions of allergies, where a quicker onset of action for a dosage form is desirable along with the convenience of administration.

Nicotine Fast Dissolving Films Made of Maltodextrins: A Feasibility Study

This work aimed to develop a fast-dissolving film made of low dextrose equivalent maltodextrins (MDX) containing nicotine hydrogen tartrate salt (NHT). Particular attention was given to the selection of the suitable taste-masking agent (TMA) and the characterisation of the ductility and flexibility under different mechanical stresses. MDX with two different dextrose equivalents (DEs), namely DE 6 and DE 12, were selected in order to evaluate the effect of polymer molecular weight on film tensile properties. The bitterness and astringency intensity of NHT and the suppression effect of several TMA were evaluated by a Taste-Sensing System. The films were characterised in term of NHT content, tensile properties, disintegration time and drug dissolution test. As expected, placebo films made of MDX DE 6 appeared stiffer and less ductile than film prepared using MDX DE 12. The films disintegrated within 10 s. Among the tested TMA, the milk and mint flavours resulted particularly suitable to mask the taste of NHT. The addition of NHT and taste-masking agents affected film tensile properties; however, the effect of the addition of these components can be counterweighted by modulating the glycerine content and/or the MDX molecular weight. The feasibility of NHT loaded fast-dissolving films was demonstrated.

Diclofenac fast-dissolving film: suppression of bitterness by a taste-sensing system

Context: The selection of a proper taste-masking agent (TMA) is a critical issue in the development of fast‐dissolving films containing bitter drugs. Objective: This work is aimed to evaluate the suppression of the bitter taste of a maltodextrin fast-dissolving film loaded with 13.4 mg sodium diclofenac (DS) by adding TMAs. Methods: The films were prepared by casting and drying aqueous mixtures of maltodextrin (DE = 6), glycerin, sorbitan oleate, and DS. Films were characterized in terms of thickness, tensile properties, film disintegration time, and drug dissolution time. The bitterness intensity of DS and the masking effect of TMAs were evaluated by an electronic tongue. Results: The ‘mint’ and ‘licorice’ flavors and sucralose mixture resulted appropriate to mask DS bitterness as confirmed by a panel of volunteers. The addition of these TMAs did not significantly affect the film disintegration time (15–20 seconds) and DS dissolution rate (about 5 minutes). Conclusion: The electronic tongue was allowed to discriminate the effect of the TMA also in the presence of other hydrosoluble constituents of the film. Therefore, because of its simplicity and rapidity, this technique could assist or even replace the sensory evaluation in the development of fast‐dissolving films.

Preparation of Fast Dissolving Films for Oral Dosage from Natural Polysaccharides.

Fast-dissolving films (FDFs) were prepared from natural polysaccharides, such as pullulan, without heating, controlling the pH, or adding other materials. The release profiles of model drugs from the films were investigated. In the absence of a drug, the casting method and subsequent evaporation of the solvent resulted in the polysaccharide forming a circular film. The presence of drugs (both their type and concentration) affected film formation. The thickness of the film was controllable by adjusting the concentration of the polysaccharide, and regular unevenness was observed on the surface of 2% pullulan film. All films prepared with polysaccharides readily swelled in dissolution medium, released the incorporated compound, and subsequently disintegrated. The release of dexamethasone from the films was complete after 15 min, although this release rate was slightly slower than that of pilocarpine or lidocaine. Therefore, FDFs prepared from polysaccharides could be promising candidates as oral dosage forms containing drugs, and would be expected to show drug dissolution in the oral cavity.

Fast dissolving films made of maltodextrins

This work aimed to study maltodextrins (MDX) with a low dextrose equivalent as film forming material and their application in the design of oral fast-dissolving films. The suitable plasticizer and its concentration were selected on the basis of flexibility, tensile strength and stickiness of MDX films, and the MDX/plasticizer interactions were investigated by ATR-FTIR spectroscopy. Flexible films were obtained by using 16–20% w/w glycerin (GLY). This basic formulation was adapted to the main production technologies, casting and solvent evaporation (Series C) or hot-melt extrusion (Series E), by adding sorbitan monoleate (SO) or cellulose microcrystalline (MCC), respectively. MCC decreased the film ductility and significantly affected the film disintegration time both in vitro and in vivo (Series C < 10 s; Series E ∼ 1 min). To assess the film loading capacity, piroxicam (PRX), a water insoluble drug, was selected. The loading of a drug as a powder decreased the film ductility, but the formulation maintained satisfactory flexibility and resistance to elongation for production and packaging procedures. The films present a high loading capacity, up to 25 mg for a surface of 6 cm 2. The PRX dissolution rate significantly improved in Series C films independently of the PRX/MDX ratio.