Mucoadhesive Films Research Articles

Optimized hydration dynamics in mucoadhesive xanthan-based trilayer vaginal films for the controlled release of tenofovir

Karaya gum, pectin and xanthan gum have been tested as candidates for manufacturing mucoadhesive trilayer films containing ethylcellulose and chitosan for the vaginal administration of the antiviral Tenofovir (TFV). The swelling profile correlated with the amount of mobile dipoles determined by impedance spectroscopy allows the determination of the hydration dynamics of these films. The fast water penetration has been demonstrated to favor the formation of polyelectrolyte complexes (PEC) via hydrogen or ionic bonds which would favor a controlled release. The incorporation of an inorganic drug release regulator induces the weakness of the polymeric chains thus enhancing the ionic mobility via the formation of low molecular weight PECs in films manufactured with karaya gum. Due to the different mechanical properties of the individual components, pectin-based films failed for a potential pharmaceutical formulation. However, mucoadhesive trilayer films produced with xanthan gum have demonstrated a moderate swelling, improved wettability and a controlled release of TFV.

A mucoadhesive biodissolvable thin film for localized and rapid delivery of lidocaine for the treatment of vestibulodynia

Vestibulodynia (VBD), an idiopathic pain disorder characterized by erythema and pain of the vulvar vestibule (the inner aspect of the labia minora and vaginal opening), is the most common cause of sexual pain for women of reproductive age. Women also feel discomfort with contact with clothing and tampon use. As most women with this disorder only have pain with provocation of the tissue, topical anesthetics applied to the vestibule are the current first line treatment for temporary pain relief. Treatment options are limited due to anatomical constraints of the vestibular region, poor drug retention time, imprecise dosing, leakage, and overall product messiness. In this study we report a novel approach to treatment of VBD using thin film designed to fit the vulvar vestibule and deliver lidocaine locally. Two use cases for VBD treatment were identified 1) rapid drug release (<5 min), for use prior to intercourse and 2) long-acting release (≥120 min) for prolonged use and relief throughout the day. Cellulose-based mucoadhesive thin films were fabricated using a solvent casting method. Three polymers including hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), and hydroxypropylmethycellulose (HMPC), were selected owing to their biocompatibility and ideal properties for film casting. Films casted with HEC, HPC, and HPMC exhibited mucoadhesive properties relative to a control, with the highest mucoadhesive force recorded for films casted with HPC. Effect of media volume, pH, presence of mucin and presence of drug on film dissolution rates were investigated. Dissolution rates were independent of media volume, media pH or drug presence, whereas faster dissolution rates were obtained for all films in presence of mucin. In vitro lidocaine release kinetics were influenced by polymer type, percent drug loading and film casting thickness. Lidocaine release was based on a diffusion mechanism rather than through film dissolution and faster release (∼5 min) was observed for HEC films compared HPC films (∼120 min). Higher drug loading and film thickness resulted in slower and more prolonged release kinetics of lidocaine. All films were biocompatible and exhibited good mechanical properties. Two film formulations (9% w/w HPC with 12% w/w LHC, 5% w/w HEC with 6% w/w LHC) were optimized to meet the two use case scenarios for VBD treatment and moved into in vivo testing. In vivo testing demonstrated the safety of the films in BALB/c mice, and the pharmacokinetic analysis demonstrated the delivery of lidocaine primarily to the vaginal tissue. We demonstrate the ability to develop a mucoadhesive, biodissolvable thin film and fine-tune drug release kinetics to optimize local delivery of lidocaine to the vulva.

Development and Evaluation of Trans Buccal Patches based on Natural and Synthetic Polymers Loaded with Rivastigmine using Solvent Casting Technique

Mucoadhesive buccal films of rivastigmine were prepared by the solvent casting technique using HPMC K15M, sodium alginate, glycerine, and Eudragit RL100. Arranged films assessed for weight variation, thickness, % drug substance, % moisture loss, % moisture take-up, folding endurance, in-vitro medicament release, and Fourier transform Infrared spectroscopy (FTIR). The films showed a controlled release (CR) over 8 h. The preparation observed to be a worthy candidate for the development of buccal patches for therapeutic purposes. Drug-polymer compatibility considers FTIR demonstrated no contradiction between the medicament and the polymers. The optimized formulation found F7 indicated drug release 85% at the end of 8 h. Thinking about the correlation coefficient (R2) values got from the kinetic equations, the drug release from the formulations F1-F8 has discovered zero-order release mechanism. It can be concluded that oral buccal patches of rivastigmine, for treatment of Alzheimer’s and Parkinson’s disease, can be formulated. The study suggests that rivastigmine can be conveniently administered orally in the form of buccal patches, with the lesser occurrence of its side effects and improved bioavailability.

Preparation of Carbopol 934 Based Ketorolac Tromethamine Buccal Mucoadhesive Film: In Vitro, Ex Vivo, and In Vivo Assessments

The goal of present investigation was to formulate and evaluate ketorolac tromethamine (KTM) mucoadhesive buccal films. The films were prepared by solvent evaporation method using PVP K30, HPMC K4M, HPMC K15M, carbopol 934, chitosan, and sodium alginate as polymers and propylene glycol as plasticizer. The films were evaluated for thickness, weight variation, folding endurance, surface pH, swelling index, in vitro residence time, in vitro diffusion, release kinetics, ex vivo permeation, in vitro-ex vivo correlation, and in vivo pharmacological activities such as anti-inflammatory and analgesic activity. Thickness, weight, drug content, and folding endurance were found to be uniform for the films. Surface pH was 6.85 ± 0.10 , and swelling index was the highest ( 27.27 ± 0.37 ) for the best film containing carbopol 934 along with sodium alginate and PVP K 30 (formulation code F2). In vitro residence time was greater than 5 h, and in vitro % drug release was 98.71% for F2. It exhibited 55.49% of swelling inhibition at 5 h, and above 38.88% was maintained at even 8 h. The film F2 has shown maximum analgesic response of 17 sec at 5 h, and the response of 11 sec was maintained at even 8 h. The anti-inflammatory and analgesic effect of F2 was found be maximum while sustaining the effect for prolonged period when compared to free drug solution. Thus, KTM mucoadhesive buccal film containing carbopol 934, sodium alginate, and PVP K30 could be an effective alternative for conventional therapy with improved efficacy.

Mucoadhesive film containing \u03b1-mangostin shows potential role in oral cancer treatment

BackgroundOral cancer is often preceded by a mucosal lesion called an oral potentially malignant disorder (OPMD). Many plant-derived compounds are of value in medicine. The objectives of this study were to develop a soluble mucoadhesive film containing α-mangostin (α-MG), a compound extracted from the peel of mangosteen fruit, and determine its activities against oral cancer cells, against human papillomavirus type 16 (HPV-16) pseudovirus, and its anti-inflammatory properties.MethodsA soluble mucoadhesive film containing α-MG was prepared. Oral squamous carcinoma cell line (SCC25), murine macrophage cells (RAW264.7), and human gingival fibroblast cell line were cultured. Anticancer activity and viability of SCC25 cells in response to α-MG film solution were determined by MTT assay. HPV-16 pseudovirus was constructed and effects of the film solution on attachment and post-attachment steps of the infection were investigated. Anti-inflammatory activity was assessed by nitric oxide (NO) inhibition. Fibroblast cell migration was determined by in vitro scratch assay.ResultsThe soluble α-MG film showed cytotoxic effects on SCC25 cells in concentration > 125 µg/ml with IC50 of 152.5 µg/ml. Antiviral activity against HPV-16 pseudovirus was observed at attachment step, but not at post-attachment step. The film also possessed a strong anti-inflammatory effect and promoted wound healing without cytotoxicity.ConclusionsMucoadhesive film containing α-MG has a cytotoxic effect on oral squamous carcinoma cell line and an inhibitory effect on HPV-16 pseudovirus at attachment step. The α-MG film also shows a potent anti-inflammatory activity and enhances wound healing. Thus, the soluble α-MG film may have a potential role in treating oral cancer.

Development of Triphala Extract-Loaded Mucoadhesive Films for Aphthous Ulcers

Triphala is a traditional Thai herbal formulation containing dried fruits of Phyllanthus emblica, Terminalia bellirica, and Terminalia chebula. It has wound healing, antioxidant and anti-inflammatory activities. The objective of this research was to formulate mucoadhesive films containing Triphala extract for aphthous ulcers treatment. The films were formulated using hydroxypropyl methylcellulose, HPMC, (5, 8, 10% w/w) as a film-forming polymer and glycerin (5% w/w) as a plasticizer. Triphala extract (2.5, 5, 10% w/w) was incorporated into the film during the film preparation. The films were then evaluated for the physical appearance, dissolution time, mechanical properties (strength and elasticity) and mucoadhesive capability to the porcine buccal mucosa. The antioxidant activity and anti-inflammatory activity of the films were also evaluated by DPPH assay and the proteins denaturation method, respectively. Physical properties revealed that Triphala-loaded HPMC films were transparent with brown color. All formulations showed 1-2 hr of dissolution times. Triphala films exhibited good mucoadhesive properties. Films prepared from the solution containing HPMC (10% w/w), glycerin (5% w/w), and Triphala extract (10% w/w) were the most appropriate formulation for further development due to suitable strength, elasticity, and mucoadhesive properties. Moreover, the films exhibited antioxidants and anti-inflammatory activity which may help relieve the symptom of aphthous ulcers.

Smart Mucoadhesive Film Former from Seeds of Arachis Hypogea and Its In-Built Properties for Pharmaceutical Applications

Aim: Isolation of novel biopolymer from Arachis hypogea seeds to be used as bio-excipient in formulation of nanosized Topiramate loaded bio-flexy films for epilepsy treatment. Method: Formulations containing nanosized Topiramate: Arachis hypogea biopolymer (in ratios of 1:0.5, 1:1; 1:3, 1:5, 1:6, 1:10) (FAO1-FAO6) were prepared by solvent casting method. Results: Arachis Hypogea Biopolymer showed percentage yield of 20% ±0.01. The biopolymer was brown in color, odourless, partially soluble in water. Its colour changing point was found to be 210ºC±2. It was tested positive for proteins and carbohydrates, amino acids were not present. Evaluation parameters of nanosized Topiramate loaded bio-flexy films containing Arachis hypogea biopolymer (FAO1-FAO6) revealed Thickness: 0.022 mm±0.004 to 0.044±0.003 mm, Folding Endurance: 140-169, Surface pH: 7.01±0.03 to 7.01±0.02, Weight Uniformity: 0.006±0.04 to 0.036±0.02, Drug Content Uniformity: 85.4%±0.68 to 93.4%±0.50, Swelling Percentage: 73%±0.6 to 89%±0.4, Percentage Moisture Uptake (PTU): 1.8%±0.10 to 2.4%±0.08, Mucoadhesion time: 45-150 minutes, Mucoretention time: 75-210 minutes. The drug release pattern for formulations FAO1-FAO6 containing Arachis hypogea biopolymer based on the T50% and T80% was found to be FAO2 (1:1) &gt; FAO5 (1:6) &gt; FAO6 (1:10) &gt; FAO1 (1:0.5)&gt; FAO4 (1:5) &gt; FAO3 (1:3). Conclusion: Based on all above-mentioned evaluation parameters, FAO2 (containing Topiramate: Arachis hypogea biopolymer (1:1)) Bio-flexy film having R2 =0.9215, Higuchi Matrix as best fit model, follows Fickian Diffusion (Higuchi Matrix) release mechanism, T50%: 44.52 hrs., T80%: 46.14 hrs. using BITS Software. Stability study revealed stable formulations. Isolated Arachis hypogea biopolymer showed in-built filmability, mucoadhesivity properties, was non-reactive and suitable for Soft Palatal Drug Delivery.

FORMULATION AND CHARACTERISATION OF MUCOADHESIVE DENTAL APPLICATIONS CONTAINING BENZYDAMINE HYDROCHLORIDE

The aim of this research was to develop a bioadhesive film based on benzydamine hydrochloride incorporated into natural bioadhesive polymers with different quantities of chitosan and guar gum but utilising a plasticiser. The obtained gels were deaerated by sonification, formed and evaporated by hot air drying; then, the properties were evaluated. Guar gum had a great influence on mechanical properties of the films – dynamic viscosity, texture, elasticity, stretching robustness, swelling and blur time. The formulations were used to obtain mucoadhesive films containing 0.3% benzydamine hydrochloride; they were tested for the release of the model drug. The amount of chitosan added to the formulation reduced the quantity of released substance and slowed down the release. Fouriertransform infrared spectroscopy did not reveal the creation of new chemical structures. In conclusion, the ratio of chitosan to guar gum in the medium impacts the mechanical properties and release parameters of the drug. These findings should enable researchers to match the parameter values to receive the most beneficial therapeutic outcome.

Gellan Gum-Based Bilayer Mucoadhesive Films Loaded with Moxifloxacin Hydrochloride and Clove Oil for Possible Treatment of Periodontitis.

Background/ObjectivePeriodontitis is a widely spread oral infection and various antibiotics are utilized for its treatment, but high oral doses and development of antibiotic resistance limit their use. This study was aimed at development of natural polymer-based mucoadhesive bilayer films loaded with moxifloxacin hydrochloride (Mox) and clove essential oil (CEO) to potentially combat bacterial infection associated with periodontitis.MethodsFilms were synthesized by double solvent casting technique having an antibiotic in the gellan gum-based primary layer with clove oil in a hydroxyethyl cellulose-based secondary layer.ResultsPrepared films were transparent, flexible, and showed high antibacterial response against both gram-positive and gram-negative bacteria. The films showed excellent pharmaceutical attributes in terms of drug content, folding endurance, swelling index, and mucoadhesive strength. Solid state characterization of formulation showed successful incorporation of drug and oil in separate layers of hydrogel structure. An in-vitro release study showed an initial burst release of drug followed by sustained release for up to 48 hours.ConclusionThe prepared mucoadhesive bilayer buccal films could be used as a potential therapeutic option for the management of periodontitis.

FORMULATION AND EVALUATION OF CILNIDIPINE MUCOADHESIVE BUCCAL FILM BY SOLVENT CASTING TECHNIQUE FOR THE TREATMENT OF HYPERTENSION

Objective: Buccal drug delivery is the most suited route for local as well as systemic delivery of drugs. Cilnidipine is an L/N type dihydropyridine 4th generation calcium channel blocker (CCB), which decreases hypertension by blocking the N-type calcium channel to attenuate vascular sympathetic neurotransmission. It has high first-pass metabolism leading to low bioavailability. Hence the present research work was undertaken to formulate mucoadhesive buccal film of Cilnidipine with an objective to enhance therapeutic efficacy, bioavailability and was developed to administer into the unconscious and less-co-operative patients. Methods: Cilnidipine buccal films were prepared by a solvent-casting technique using various concentrations of mucoadhesive-polymers such as Hydroxyl propyl methylcellulose (HPMC) E15 and K4M and ethyl-cellulose as backing-layer, which acts like a patch providing unidirectional drug release. Prepared films were evaluated for their weight variation, thickness, surface-pH, swelling-index, drug content uniformity, in vitro residence time, folding endurance, tensile strength, in vitro release and permeability studies. Results: The infra-red (IR) spectra showed no interaction, and Physico-chemical characteristics were found within the limit. Swelling of the film increases with increasing concentration of polymers and %drug content of all formulations found to be in the range of 92.13%±0.94% to 97.92%±0.35%. The formulation F5, showed a promising tensile strength, folding endurance and in vitro drug release of about 95.18±0.03%, thus can be selected as an optimized formulation of mucoadhesive buccal film. Conclusion: The formulation of Cilnidipine mucoadhesive buccal film was found to be satisfactory and reasonable.

Solid and Semisolid Innovative Formulations Containing Miconazole-Loaded Solid Lipid Microparticles to Promote Drug Entrapment into the Buccal Mucosa.

The currently available antifungal therapy for oral candidiasis (OC) has various limitations restricting its clinical use, such as short retention time, suboptimal drug concentration and low patients compliance. These issues could be overcome using micro or nanotechnology. In particular, solid lipid microparticles (SLMs) resulted as a particularly promising penetration enhancer carrier for lipophilic drugs, such as the antifungal miconazole (MCZ). Based on these considerations, cetyl decanoate (here synthesized without the use of metal catalysis) was employed together with 1-hexadecanol to prepare MCZ-loaded SLMs. These resulted in a powder composed of 45–300 µm diameter solid spherical particles, able to load a high amount of MCZ in the amorphous form and characterized by a melting temperature range perfectly compatible with oromucosal administration (35–37 °C). Moreover, when compared to Daktarin® 2% oral gel in ex vivo experiments, SLMs were able to increase up to three-fold MCZ accumulation into the porcine buccal mucosa. The prepared SLMs were then loaded into a buccal gel or a microcomposite mucoadhesive buccal film and evaluated in terms of MCZ permeation and/or accumulation into porcine buccal mucosa by using lower doses than the conventional dosage form. The promising results obtained highlighted an enhancement in terms of MCZ accumulation even at low doses. Furthermore, the prepared buccal film was eligible as stable, reproducible and also highly mucoadhesive. Therefore, the formulated SLMs represent a penetration enhancer vehicle suitable to reduce the dose of lipophilic drugs to be administered to achieve the desired therapeutic effects, as well as being able to be effectively embedded into easily administrable solid or semisolid dosage forms.

Cytokine-Related Effect of Buccal-Delivered Collagen Peptide Incorporated in Mucoadhesive Films to Improve Female Skin Conditions

Recently, interest in collagen products has increased in the industries However, collagen products that are taken orally have the problem of being degraded by digestive enzymes. Therefore, a collagen peptide buccal delivery film (C-BDF) was developed to enhance the absorption without destruction and a clinical trial was conducted. A C-BDF was developed as a double layer and the permeation of collagen peptide (CP) through swine mucosa was investigated. This clinical study was performed on 43 healthy women, who were divided into either a control (n = 21) or test group (n = 22), over the course of 4 weeks. Skin assessments analyzed the hydration, elasticity, and roughness. In addition, the production of peroxynitrite and IL-1α in RAW 264.7 cells in supernatant media was conducted. A total of 1 kDa of CP in BDF showed significantly stronger permeation through swine mucosa compared to 3 kDa of CP in BDF. The C-BDF significantly enhanced skin hydration, elasticity, and roughness, and it removed wrinkles with no side effects after 2 weeks of intake. In addition, the production of peroxynitrite and IL-1α after the treatment with CP was significantly increased. Therefore, this study showed that collagen peptides could be completely absorbed into mucosa via a buccal delivery system and homeopathic effects might occur.

An Updated Overview of the Emerging Role of Patch and Film-Based Buccal Delivery Systems.

Buccal mucosal membrane offers an attractive drug-delivery route to enhance both systemic and local therapy. This review discusses the benefits and drawbacks of buccal drug delivery, anatomical and physiological aspects of oral mucosa, and various in vitro techniques frequently used for examining buccal drug-delivery systems. The role of mucoadhesive polymers, penetration enhancers, and enzyme inhibitors to circumvent the formulation challenges particularly due to salivary renovation cycle, masticatory effect, and limited absorption area are summarized. Biocompatible mucoadhesive films and patches are favored dosage forms for buccal administration because of flexibility, comfort, lightness, acceptability, capacity to withstand mechanical stress, and customized size. Preparation methods, scale-up process and manufacturing of buccal films are briefed. Ongoing and completed clinical trials of buccal film formulations designed for systemic delivery are tabulated. Polymeric or lipid nanocarriers incorporated in buccal film to resolve potential formulation and drug-delivery issues are reviewed. Vaccine-enabled buccal films have the potential ability to produce both antibodies mediated and cell mediated immunity. Advent of novel 3D printing technologies with built-in flexibility would allow multiple drug combinations as well as compartmentalization to separate incompatible drugs. Exploring new functional excipients with potential capacity for permeation enhancement of particularly large-molecular-weight hydrophilic drugs and unstable proteins, oligonucleotides are the need of the hour for rapid advancement in the exciting field of buccal drug delivery.

Development and optimization of a new tioconazole vaginal mucoadhesive film using an experimental design strategy. Physicochemical and biological characterization

A new tioconazole (TCZ) mucoadhesive film, based on a biodegradable chitosan/ hydroxypropyl methylcellulose (CH/HPMC) blend, was developed for treatment of vaginal candidiasis. The formulation was optimized through an I-optimal design (minimizing the integral of the prediction variance across the factor space), where the impact of the proportion of the ingredients and processing variables on the quality of the final product was evaluated. Both, the thickness of the film and the swelling index, which affect patients’ comfort and compliance, were considered. Mechanical testing, such as load at break, elongation at break, and mucoadhesive strength were also included as dependent variables.The optimal mucoadhesive film formulation, which should be obtained at a drying temperature of 30 °C, was found to include the combination of CH and HPMC (forming polymers) at 0.25:0.75 ratio, a mixture of polyethylene glycol 400 and propylene glycol as plasticizers (0.07:0.93, 5% w/w), and TCZ loaded at 15 % w/w.The optimal preparation was subjected to exhaustive characterization studies, which revealed that the drug was entrapped in the polymeric matrix in an amorphous state and that the film exhibited a smooth and uniform surface, demonstrating excellent component compatibility. In vitro tests showed that the formulation has an excellent time to kill value (3 min) and lacks cytotoxicity, suggesting that it should be highly effective and safe.

Design of Mucoadhesive Strips for Buccal Fast Release of Tramadol

Tramadol hydrochloride is a synthetic analogue of codeine and shows activity on the central nervous system as an opioid agonist and inhibitor of serotonin and norepinephrine reuptake. It has been used for controlling moderate to severe pain. Mucoadhesive fast-dissolving films can present greater drug availability and patient acceptance when compared to the systems of peroral administration. The films were prepared using the solvent casting method with ethylcellulose, polyvinylpyrrolidone and poly(vinyl alcohol). The effect of each polymer concentration was investigated using a 2³ factorial design with repetition at the central point. The formulations were subjected to physicochemical, mechanical, ex vivo mucoadhesive and in vitro drug release profile analysis. These properties were dependent on the polymeric composition (independent factors) of each system. The optimized formulations showed good macroscopic characteristics, improved resistance to bending, rigidity, rapid swelling up to 60 s, improved mechanical and mucoadhesive characteristics, and also fast dissolving and tramadol release. The optimized formulations constitute platforms and strategies to improve the therapy of tramadol with regard to availability at the site of application, considering the necessity of rapid pain relief, and show potential for in vivo evaluation.

Development and Optimisation of Mucoadhesive Films for Enhanced Drug Delivery in Treatment of Lichen Planus

Introduction: Mucoadhesive buccal films are most recently developed and preferred over buccal tablet because of the flexibility, better bioavailability, cost effectiveness, and good patient compliance it offers&#x0D; Objective: The study aimed to formulate mucoadhesive films of Clobetasol Propionate with reduced side effects, controlled release and better patient compliance, suitable for the management of oral lichen planus.&#x0D; Methods: Clobetasol Propionate Buccal Films were prepared by the incorporation of the Clobetasol Propionate along with polymers like Hydroxy Propyl Methyl Cellulose (HPMC) K4M, polyethylene glycol 400 and glycerol by solvent casting method.&#x0D; Results: The drug content of all the formulations was found to be 85.04% to 93.14%. The swelling index of all formulations of Clobetasol Propionate mucoadhesive buccal film was found to be 82% to 94.07%. Formulation F14 which contains Hydroxy Propyl Methyl Cellulose K4M (1%), and polyeth­ylene glycol 400 (1%) exhibited better results compared to other combination of polymers in different concentration. It showed swelling index of 94.07%. Drug content was found to be 91% and showed release of drug up to 95.05% in 12 hours. The optimised formula showed no significant changes on stability studies when stored at 40ºC/75% RH for three months.&#x0D; Conclusions: The application of mucoadhesive buccal film containing Clobetasol Propionate appeared to be effective, avoiding the side effects and the data obtained in the study suggested that buccal films can be successfully designed to give controlled drug delivery.

A comparison between solvent casting and electrospinning methods for the fabrication of neem extract-containing buccal films

In the present study a double layer mucoadhesive buccal film containing nanocarriers encapsulated with neem extract was fabricated through electrospinning and solvent casting techniques for dental therapeutic applications. The morphological, physical and mucoadhesive properties of the resulting electrospun and solvent cast oral films were mutually compared, and their drug release behavior and antibacterial activity were further investigated. Chitosan/poly(vinylalcohol) (PVA) as a mucoadhesive component and phenylalanine amino acid nanotubes (PhNTs)-containing neem extract as a drug nanocarrier were used to fabricate oral films. A poly(caprolactone) (PCL) layer was used as an impermeable backing layer to protect the mucoadhesive component from tongue movement and drug loss. The results indicated an interconnected porous and fully filled solid structures for electrospun and solvent cast films, respectively. The physicomechanical parameters of the samples such as pH, weight, thickness, folding endurance and tensile strength were also evaluated. The crosslinked electrospun buccal film indicated better swelling and mucoadhesive properties compared to the solvent cast film. In addition, the drug loading capacity and encapsulation efficiency of the solvent cast film showed lower experimental values than those of electrospun oral film. On the other hand, the electrospun oral film had a well-controlled release of neem extract up to 82% at oral pH, which is best fitted to the Weibull model, and demonstrated the highest antibacterial properties against S. mutans bacteria with high biocompatibility on L929 fibroblast cells. Generally, the synthesized electrospun mucoadhesive film has a better potential for oral therapeutic applications than the solvent cast film.

Quality by Design Approach in the Formulation of Glibenclamide Mucoadhesive Buccal Films

Glibenclamide, an oral hypoglycemic BCS class II drug that gets completely metabolized in the liver, serves as a suitable candidate for buccal drug delivery. The study aims to formulate and evaluate mucoadhesive buccal films (MBF) of Glibenclamide by Quality by Design approach to ensure the quality of a developed product. Initially, Plackett Burman Design was used as a screening method to determine the factors affecting the characteristics of the MBF. The selected factors were further evaluated using 32 full factorial design for confirming the effect of these variables. Responses like Drug release, mucoadhesion time, permeability were considered the main Critical Quality Attributes. The film was evaluated for swelling, mucoadhesion, folding endurance, permeability, drug release. Contour and surface response plots were used to determine the design space (DS). The formulated film gave a robust design within 1.3-1.7 % for HPMC K 15M and 0.5-1.5 % for glycerin. The optimized formulation prepared within the DS showed in-vitro drug release (80.11%), mucoadhesive strength (60.3 g), and ex-vivo permeation (82.85 %), which lies within pre-determined full ranges of Quality Target Product Profile (QTTP). The optimized formulation within the DS was in good agreement with QTPP, which ensures the accuracy and robustness of the formulation.

Development and evaluation of a composite dosage form containing desmopressin acetate for buccal administration

Desmopressin acetate (DDAVP) is an oligopeptide indicated for the treatment of primary nocturnal enuresis, for example. The poor oral bioavailability of DDAVP accelerated a shift to alternative routes of administration like nasal and oromucosal, whereby nasal administration results in high fluctuations increasing the risk of undesirable side effects. Aim of the study was to use a new composite dosage form (solid matrix attached to a bilayer mucoadhesive film) to make DDAVP available via oromucosal route, reducing the risk of undesirable side effects through precise dosing. DDAVP was incorporated into a solid matrix in the form of a minitablet, and both direct tableting (AV > 30) and granulation followed by tableting (AV = 17.86) were compared. Minitablets with content uniformity could only be obtained by granulation and loss supplementation (AV = 11.27) with immediate drug release (>80% after 7–8 min) and rapid disintegration (<49 s). Permeation studies were performed with a clinically relevant dose (200 μg) in a time interval of up to one hour, resulting in apparent permeation coefficients of 4.90 × 10−6 cm/s (minitablet) and 2.04 × 10−6 cm/s (composite). Comparable fluctuations showed no inferiority of composite and minitablet regarding dosing accuracy. Thus, a step towards controlled and dose-accurate transmucosal delivery of systemically active DDAVP could be achieved.

Establishment of a Dissolution Test System for the Biorelevant Characterization of Esophageal Applied Dosage Forms

There is a high demand for drug delivery systems that enable local therapy of esophageal diseases such as eosinophilic esophagitis. For the development of such drug delivery systems, suitable in vitro test procedures are needed that allow a biorelevant characterization of dosage forms. With the help of the new test system presented in this thesis it is now possible to simulate the application site esophagus and to characterize the dissolution behavior of esophageal applied drug delivery systems under special consideration of physiological parameters like salivary flow rate, intensity of peristalsis, and posture of the patient. In this work, the dissolution of mucoadhesive films for esophageal application with the new device was investigated and compared to the results obtained with the compendial standard device (USP 2 apparatus). The results show that the novel test system is a promising tool for the early evaluation of locally applied oral formulations for esophageal application.