Oral Thin Film Research Articles

Formulation and Evaluation of Swellable Oral Thin Film of Metoclopramide Hydrochloride

Traditionally metoclopramide hydrochloride is used as an antiemetic in migraine & cancer patients and in controlling post-operative nausea and vomiting. The main aim of this study was to develop a swellable oral thin film for the treatment of the mentioned pathological conditions. This swellable thin film formulation is specially designed for paediatric patients for oral administration, where it will swell up when exposed to saliva in the oral cavity and will be easily swallowed by the patient, without the need for water. Nine formulations of swellable oral thin film of metoclopramide hydrochloride such as F1 to F9 were prepared by solvent casting method. The drug-Povidone K90 ratio were 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8 and 1:9, respectively. Various physicochemical evaluations including weight variation, thickness, folding endurance, in vitro dissolution studies, content uniformity, FTIR, Trinocular microscopic imaging and swelling property of film were conducted. It was observed that thickness and weight of film was directly proportional to the total solid content of the film (F1 showed the lowest thickness and weight and F9 showed the highest). All the batches revealed content uniformity between 98.0% to 101.0% and cumulative drug release between 94.8% and 102.4%. Swelling behavior of film was inversely proportional to the quantity of Povidone K90 in the film. Formulation F1 showed the highest linear expansion co-efficient (L%) and percentage increase in weight due to swelling while F9 demonstrated the lowest corresponding to the quantity of Povidone K90. Quantity of glycerin and Povidone K90 affected the appearance and peeling of the films. F1, F2 and F3 had lowest quantity of glycerin and Povidone K90 and were least glossy and easier to peel out and F7, F8 and F9 with highest quantity of glycerin and Povidone K90 and were glossiest but hardest to peel out. DOI: http://dx.doi.org/10.3329/bpj.v17i1.22325 Bangladesh Pharmaceutical Journal 17(1): 102-112, 2014

Full factorial design, physicochemical characterization of phenylephrine HCl loaded oral thin film

Full factorial design, physicochemical characterization of phenylephrine HCl loaded oral thin film

In vitro dissolution testing of oral thin films: A comparison between USP 1, USP 2 apparatuses and a new millifluidic flow-through device

Thin strips of polymeric films have been recently proposed as a promising drug delivery alternative for non-compliant patients (geriatric, children, bedridden) and different therapeutic classes (e.g. vaccines, peptides and nanoparticles).In this work, a new millifluidic continuous flow-through device is proposed for dissolution studies of oral dissolving strips. The millifluidic device is covered by patent. The flow-through device mimics mouth physiological conditions thanks to the laminar tangential solvent flow, flow rates order of 1mL/min and low hold-up volume (1cm3). Pilot dissolution tests have been performed on commercially available melatonin strips with different initial drug loadings and thicknesses. Dissolution profiles obtained with the flow-through device are compared with those obtained using the official USP XXXVII basket (USP 1) and paddle (USP 2) apparatuses.

Preparation, Characterization and <i>In Vitro</i> Drug Release Studies of 6-mercaptopurine Thin Film

Oral thin films of 6-mercaptopurine were fabricated from mucoadhesive polymer, chitosan and polyvinylpyrrolidone for the purpose of prolonging drug release and improving its bioavailability. All fabricated film formulations prepared were smooth and translucent, with good flexibility. The weight and thickness of all the formulations were found to be uniform. These films were also evaluated for surface pH, folding endurance, swelling percentage (% S) and in vitro disintegration time. Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) were used to evaluate the physico-chemical nature of the films. In-vitro drug release have shown enhanced release profiles for thin films compared to pure drug and the release patterns have been found to be pH dependant. The results of the study reveals that fabrication of 6-MP oral thin film by using solvent cast technology is a simple and an efficient method for drug delivery to achieve desired therapeutic compliance.Keywords: 6-mercaptopurine; In Vitro Drug Release; SEM; FTIR

Design of freeze-dried Soluplus/polyvinyl alcohol-based film for the oral delivery of an insoluble drug for the pediatric use

Spironolactone (SL) is a poorly water-soluble drug. Being poorly soluble affects its dissolution rate which in turn affects its oral bioavailability. This work aimed to prepare freeze-dried SL-Soluplus®/polyvinyl alcohol (PVA) oral thin film in an attempt to enhance the drug solubility on one hand and at the same time prepare a solid dosage form convenient for the pediatric use. SL-Soluplus®/PVA films were prepared using polyethylene glycol 400 (PEG 400) as a plasticizer applying the solvent-casting technique. The prepared films were evaluated for their thickness, tensile strength, and in vitro dissolution studies. Box–Behnken design (17 runs) was applied to optimize the effects of the formulation variables on the film properties. The optimized film formulation was freeze-dried after casting so as to enhance the drug dissolution. Moreover, the optimized freeze-dried film was re-characterized in vitro and evaluated in vivo in human volunteers to investigate its palatability and satisfaction. The results showed that the optimized formulation composed of 10% polymer concentration containing Soluplus®:PVA (0.33:0.66) and plasticized with 30% PEG 400 possessed the highest desirability value (0.836). Freeze-drying of the optimized formulation succeeded to improve SL in vitro dissolution due to the preparation of a more porous film compared to the non-freeze-dried one. In vivo evaluation of the optimized freeze-dried film showed high satisfaction among the participating volunteers concerning the ease of administration and sensation thereafter, where all the film specimens dissolved without the need for water and no film residues remained in the mouth following film dissolution. In conclusion, freeze-dried Soluplus®/PVA-based oral thin film proved to be a successful carrier for the oral delivery of insoluble drugs like SL for pediatrics.

Polyvinylpyrrolidone oral films of enrofloxacin: film characterization and drug release.

Enrofloxacin is a fluoroquinolone derivative used for treating urinary tract, respiratory and skin infections in animals. However, low solubility and low bioavailability prevented it from using on humans. Polyvinylpyrrolidone (PVP) is an inert, non toxic polymer with excellent hydrophilic properties, besides it can enhance bioavailability by forming drug polymer conjugates. With the aim of increasing solubility and bioavailability, enrofloxacin thin films were prepared using PVP as a polymer matrix. The obtained oral thin films exhibited excellent uniformity and mechanical properties. Swelling properties of the oral thin films revealed that the water uptake was enhanced by 21%. The surface pH has been found to be 6.8±0.1 indicating that these films will not cause any irritation to oral mucosa. FTIR data of the oral thin films indicated physical interaction between drug and polymer. SEM analysis revealed uniform distribution of drug in polymer matrix. In vitro drug release profiles showed enhanced release profiles (which are also pH dependant) for thin films compared to pure drug. Antibacterial activity was found to be dose dependent and maximum susceptibility was found on Klebsiella pneumonia making this preparation more suitable for respiratory infections.

Reflectance infrared spectroscopy for in-line monitoring of nicotine during a coating process for an oral thin film

A process analytical method using reflectance infrared spectrometry was developed for the in-line monitoring of the amount of the active pharmaceutical ingredient (API) nicotine during a coating process for an oral thin film (OTF). In-line measurements were made using a reflectance infrared (RI) sensor positioned after the last drying zone of the coating line. Real-time spectra from the coating process were used for modelling the nicotine content. Partial least squares (PLS1) calibration models with different data pre-treatments were generated. The calibration model with the most comparable standard error of calibration (SEC) and the standard error of cross validation (SECV) was selected for an external validation run on the production coating line with an independent laminate. Good correlations could be obtained between values estimated from the reflectance infrared data and the reference HPLC test method, respectively. With in-line measurements it was possible to allow real-time adjustments during the production process to keep product specifications within predefined limits hence avoiding loss of material and batch.

An Introduction to Fast Dissolving Oral Thin Film Drug Delivery Systems: A Review

Many pharmaceutical companies are switching their products from tablets to fast dissolving oral thin films (OTFs). Films have all the advantages of tablets (precise dosage, easy administration) and those of liquid dosage forms (easy swallowing, rapid bioavailability). Statistics have shown that four out of five patients prefer orally disintegrating dosage forms over conventional solid oral dosages forms. Pediatric, geriatric, bedridden, emetic patients and those with Central Nervous System disorders, have difficulty in swallowing or chewing solid dosage forms. Many of these patients are non-compliant in administering solid dosage forms due to fear of choking. OTFs when placed on the tip or the floor of the tongue are instantly wet by saliva. As a result, OTFs rapidly hydrate and then disintegrate and/or dissolve to release the medication for local and/or systemic absorption. This technology provides a good platform for patent non- infringing product development and for increasing the patent life-cycle of the existing products. The application of fast dissolving oral thin films is not only limited to buccal fast dissolving system, but also expands to other applications like gastroretentive, sublingual delivery systems. This review highlights the composition including the details of various types of polymers both natural and synthetic, the different types of manufacturing techniques, packaging materials and evaluation tests for the OTFs.

Novel probiotic dissolvable carboxymethyl cellulose films as oral health biotherapeutics: in vitro preparation and characterization

Objectives: Oral health is influenced by the mouth's resident microorganisms. Dental caries and periodontitis are oral disorders caused by imbalances in the oral microbiota. Probiotics have potential for the prevention and treatment of oral disorders. Current formulations, including supplements and foods, have limitations for oral delivery including short storage time, low residence time in the mouth, effects on food consistency, and low patient compliance. Oral thin films (OTFs) may be efficient in delivering probiotics to the mouth. This research aims to develop a novel carboxymethyl cellulose (CMC)-probiotic-OTF to deliver probiotics for the treatment/prevention of oral disorders.Methods: CMC-OTFs were developed with varying CMC concentration (1.25 – 10 mg/mL), weight (5 – 40 g), thickness (16 – 262 μm), hygroscopicity (30.8 – 78.9 mg/cm2 film), and dissolving time (135 – 600 s). The 10 g 5 mg/mL CMC-OTF was selected and used to incorporate Lactobacillus fermentum NCIMB 5221 (6.75 × 108 cells/film), a probiotic with anti-inflammatory potential for periodontitis treatment and capable of inhibiting microorganisms responsible for dental caries and oral candidiasis.Results: The CMC-OTF maintained probiotic viability and antioxidant activity following 150 days of storage with a production of 549.52 ± 26.08 μM Trolox equivalents.Conclusion: This research shows the successful development and characterization of a novel probiotic-CMC-OTF with potential as an oral health biotherapeutic.

Mass transfer through laminar boundary layer in microchannels with nonuniform cross section : The effect of wall shape and curvature

This paper provides an analytical solution for the combined diffusive and convective mass transport from a surface film of arbitrary shape at a given uniform concentration to a pure solvent flowing in the creeping regime through microchannels.This problem arises e.g. in the study of swelling and dissolution of polymeric thin films under the tangential flow of solvent, modeling the oral thin film dissolution for drug release towards the buccal mucosa or oral cavity.We present a similarity solution for mass transfer in laminar forced convection. The classical boundary layer solution of the Graetz-Nusselt problem, valid for straight channels or pipes, is generalized to a microchannel with rectangular cross-section varying continuously along the axial coordinate.Close to the curved releasing boundary hs(s), parametrized by a curvilinear abscissa s, both the tangential vt(r,s) and the normal velocity vn(r,s) components play a role in the dissolution process, and their scaling behavior as a function of wall normal distance r should be taken into account for an accurate description of the concentration profile in the boundary layer. An analytic expression for the local Sherwood number as a function of the curvilinear abscissa and the Peclet number is presented.

Fast Dissolving Films: A Review

Fast-dissolving drug delivery systems have been developed as an alternative to conventional dosage form as an oral means of drug delivery in case of chronic conditions. Now a day's fast dissolving films are preferred over conventional tablets and capsules for masking the taste of bitter drugs to increase the patient compliance. Fast dissolving films consist of a very thin oral strip which dissolves in less than one minute when placed on the tongue. Dissolvable oral thin films are in the market since past few years in the form of breath strips and are widely accepted by consumers for delivering vitamins, vaccines and other drug products. The various manufacturing techniques for the preparation of films have also been detailed in the review. The present review details most of the patents on such fast dissolving films in recent years. A brief study has been made on various parameters which are used to evaluate such films. In case of chronic disorders these fast dissolving films are better for delivering drugs and obtaining faster therapeutic blood levels and superior in comparison to other oral conventional dosage forms.

Formulation development of fast releasing oral thin films of levocetrizine dihydrochloride with Eudragit® Epo and optimization through Taguchi orthogonal experimental design

The aim of this study was to develop a fast releasing oral polymeric film, prepared using the solvent casting method, with good mechanical properties, instant disintegration and dissolution, an acceptable taste in the oral cavity. Levocetirizine dihydrochloride, an antihistamine, was incorporated to relieve the symptoms of allergic rhinitis. Four batches of films with drug were prepared using different combinations of polymers and plasticizers Eudragit® EPO, HPMC E 5 LV, and PVA were the selected polymers. Glycerin, dibutyl phthalate, propylene glycol, and PEG 400 were the selected plasticizers.The resultant films were evaluated for weight variation, assay, content uniformity, folding endurance, thickness, tensile strength, percent elongation, surface pH, in vitro disintegration and in vitro dissolution.The formulations from the preliminary trial were analyzed using Taguchi OA experimental design, which was applied to optimize the type of polymers, concentration of polymers, plasticizer, and sweetener based on their disintegration data at three different levels.The optimized films disintegrated in less than 30s, releasing 70-90% of drug within 2 mins.The percentage release varied with the type of polymer and concentration of polymer. The films made with EPO released 96% of drug in 2 mins, which was the best release among all.

Formulation development of fast releasing oral thin films of levocetrizine dihydrochloride with Eudragit®Epo and optimization through Taguchi orthogonal experimental design

Formulation development of fast releasing oral thin films of levocetrizine dihydrochloride with Eudragit^®Epo and optimization through Taguchi orthogonal experimental design

Preparation of a fast dissolving oral thin film containing dexamethasone: A possible application to antiemesis during cancer chemotherapy

We prepared fast dissolving oral thin film that contains dexamethasone and base materials, including microcrystalline cellulose, polyethylene glycol, hydroxypropylmethyl cellulose, polysorbate 80 and low-substituted hydroxypropyl cellulose. This preparation showed excellent uniformity and stability, when stored at 40 °C and 75% in humidity for up to 24 weeks. The film was disintegrated within 15 s after immersion into distilled water. The dissolution test showed that approximately 90% of dexamethasone was dissolved within 5 min. Subsequently, pharmacokinetic properties of dexamethasone were compared in rats with oral administration of 4 mg dexamethasone suspension or topical application of the film preparation containing 4 mg dexamethasone to the oral cavity. Pharmacokinetic parameters were similar between the two groups in which C max (h), T max (μg/mL), AUC (μg/mL/h) and half-life (h) were 12.7 ± 6.6 (mean ± SD, N = 10), 3.4 ± 1.4, 93.6 ± 37.8 and 1.66 ± 0.07, respectively, for oral suspension and 13.3 ± 4.0, 3.2 ± 1.0, 98.0 ± 22.3 and 1.65 ± 0.06, respectively, for film preparation. These findings suggest that the fast dissolving oral thin film containing dexamethasone is likely to become one of choices of dexamethasone preparations for antiemesis during cancer chemotherapy.