Buccal Drug Delivery System Research Articles

Optimization and comparison of unidirectional lidocaine-loaded buccal patch with the articaine-loaded buccal patch to reduce injection pain and increment of patients' compliance in dental procedures: A double‐blind randomized controlled trial

IntroductionNervous patients often postpone dental visits until they are in severe pain, exacerbating anxiety. Buccal patches provide a noninvasive method of delivering drugs between the upper gum and cheek, offering local and systemic effects. Prior research has demonstrated the effectiveness, safety, and reliability of topical lidocaine or articaine patches for oral anesthesia. Consequently, this study aimed to develop a three-layered buccal drug delivery system for topical anesthetics. MethodsThe first step was preparing and optimizing lidocaine-loaded three-layer patches using Design-expert software. The effects of ethylcellulose, Eudragit, and carbopol concentrations were investigated on patch characteristics, including mucoadhesion, Young's modulus, and Elongation-at-break. Subsequently, patches were fabricated according to the optimized formulation determined by the software, and their efficacy was studied in a randomized, double-blind clinical trial. Participants received either lidocaine or articaine-loaded compared with placebo in a split-mouth study. They evaluated their pain levels using the Visual Analogue Scale (VAS), and the onset and duration of action were recorded for each treatment. ResultsAccording to the results, increasing ethyl cellulose and Eudragit concentrations improved mucoadhesion force (p < 0.05) while increasing ethyl cellulose and reducing Eudragit concentrations increased Young's modulus (p < 0.05). Increasing Carbopol and decreasing Eudragit concentrations also raised elongation at break significantly in the patch (p < 0.05). Treatment with lidocaine-loaded patches resulted in lower VAS scores and faster onset of action in patients than articaine-loaded patches. However, the duration of the effect was longer in the former(p < 0.001). ConclusionBased on the responses' analysis, the formulation of the 3-layered buccal patch was optimized. This formulation comprised 4.72 % ethyl cellulose, 2 % Carbopol, and 5 % eudragit. Clinical evaluation results showed that loading the optimized formulation with lidocaine was more efficient in controlling the injection pain than articaine. Trial registrationThis trial was prospectively registered with irct.behdasht.gov.ir (registration number: IRCT20210118050067N2) on Aug 19, 2022.

Mucoadhesive Buccal Tablet Formulation of Azithromycin dihydrate for treatment of Upper Respiratory Tract Infection

The buccal drug delivery system is a versatile delivery system which can be designed for local or systemic effect. The objective of the study was to developed patient complacent tablet which can give sustain release of antibacterial agent for relief of upper respiratory tract infection. Azithromycin dihydrate is a semi-synthetic macrolide antibiotic widely used to prevent bacterial infections in the upper respiratory tract. The mucoadhesive buccal tablets of azithromycin dihydrate were formulated by varying concentrations of polymers (natural and synthetic), glidant and other excipients. The drug-excipient compatibility studies were carried out through DSC and FTIR studies. The selected excipients were found to be compatible. Further the dry blend of drug-excipients was evaluated for pre-compression properties. The prepared tablets were evaluated as per the general monograph for tablets of IP. The studies were also carried out to evaluate sustained release of the drug and mucoadhesivity of the tablets. A 23 level (2 level and 3 factors) factorial design was navigated to study the effect of natural, synthetic polymers and the glidant on mucoadhesive strength and percentage cumulative drug release at 8 hours. The responsive variables were analysed using ANOVA by Design-Expert version 12.0. It was concluded that these excipients significantly affected the response variables. The optimized tablet formulation was found to have an adequate mucoadhesion and a cumulative percentage release. The final product was performed for accelerated stability studies, optimized formulation was found to be stable at room temperature and accelerated temperature for three months.

Effect of Formulation Parameters on Enalapril Maleate Mucoadhesive Buccal Tablet Using Quality by Design (QbD) Approach.

The buccal route has great prospects and possible benefits for the administration of drugs systemically. The present study involves designing, developing and optimising the buccal tablet formulation of Enalapril Maleate (EM) by using the QbD approach. We prepared the EM buccal tablets using the dry granulation method. In the QTPP profile, the CQAs for EM buccal tablets are Mucoadhesive strength, swelling index and drug release (dependent variables); the CMAs identified for EM buccal tablets were Carbopol 934P, HPMC-K100M and chitosan (independent variables). Diluent quantity, blending time and compression force were selected as CPPs; the Box-Behnkentdesign was used to evaluate the relationship between the CMAs and CPPs. Based on the DoE, the composition of the optimised formulation of EM BT-18 consists of 20mg of EM, 15 mg of carbopol 934p, 17 mg of HPMC-K100M, 10mg of chitosan, 30 mg of PVP K-30, 1 mg of magnesium stearate, 16 mg of Mannitol, 1 mg of aspartame, and 50 mg of Ethyl cellulose. The optimised formulation of EM BT 18 was found to have a Mucoadhesive strength of 24.32±0.30g. The swelling index was 90.74±0.25% and drug release was sustained up to 10 hours 98.4±3.62% compared to the marketed product, whose release was up to 8 hours. We attempted to design a buccal tablet of Enalapril Maleate for sustained drug release in the treatment of hypertension. Patients who cannot take oral medication due to trauma or unconscious conditions could receive the formulation. Development of a newly P.ceutical product is very time-consuming, extremely costly and high-risk, with very little chance of a successful outcome. Hence, this study showed EM tablets are already available on the market but we have chosen a buccal drug delivery system using a novel approach using QbD tools to target the quality of the product accurately.

Buccal Patches: A Comprehensive review

The buccal mucosa is one of the administration sites that might provide an alternative for peroral administration. The successful delivery of drugs across the oral mucosa represents a continuing challenge, as well as a great opportunity. Buccal delivery, has progressed far beyond the use of traditional dosage forms with novel approaches emerging continuously. Buccal drug delivery system in which drug enters directly in systemic circulation thereby by passing the first pass effect. This is painless and without discomfort, precise dosage form and facilitates ease of removal without significant associated pain. Moreover it shows better stability, patient compliance; uniform and sustained drug release and above all easy and cheap methods of preparation which can be done with various commonly available biocompatible polymers. The buccal route has been researched for a wide variety of drugs and has gained significant attention and momentum since it offers remarkable advantages. Over past few decades, buccal route for systemic drug delivery using mucoadhesive polymers to significantly improve the performance of many drugs has been of profound interest. Present article deals with the different aspect of the buccal patches.

The use of electrospinning in the development of systems for buccal drug delivery: a review

Electrospinning is a simple, low cost and versatile technology used for the manufacture of nanomaterials. The electrospun nanofibers produced are characterized by high porosity and large specific surface area, factors that make the membranes potentially useful in the development of systems for drug release. When it comes to drug release in the oral cavity, the nanofibers are highlighted due to the advantage of easy modulation of the drug release profile, by monitoring the morphology, porosity, chemical composition of the fibers and the electrospinning technique. In this sense, this study developed a literature review on the use of the electrospinning technique to obtain buccal drug delivery systems. Scientific articles published in the databases Science Direct and Embase were used, with the following descriptors and their combinations: [electrospinning] and [buccal drug delivery]. Articles published between 2013 and 2023 were considered. For the inclusion of the studies, the following criteria were used: articles published in English, experimental studies, and the descriptors should appear in the title, abstract, or keywords. Fourteen articles were included in the final analysis and from them it was verified the wide use of the electrospinning technique for the development of buccal drug delivery systems and the employment of active substances of various pharmacological classes. The analyzed studies conclude that the use of electro-spinning of drugs associated with other pharmaceutical excipients are promising tools in the development of drug delivery systems in the oral cavity, since they avoid first-pass hepatic metabolism, enzymatic degradation of the drug, present ease of administration and allow easy removal of the system in case of adverse events.

Mucoadhesive Buccal Films

Pharmaceutical formulations are experiencing a significant transformation as novel drug delivery techniques become increasingly available and effective. While there are many different types of medical dosage forms, each has its own limitations, such as tablet choking and painful parenteral dosages. Buccal drug delivery, which involves administering medication to the oral cavity, offers a convenient and easy-to-administer alternative. The oral route of medication administration has numerous benefits, including avoiding liver metabolism, enhancing drug bioavailability, and improving the onset of action. By directly entering the systemic circulation, active pharmaceutical ingredients can produce their therapeutic effects. As the buccal mucosa has a high degree of permeability and blood supply, it is a highly accessible drug delivery system. There are six theories that explain mucosal adhesion: electronics, wettability, adsorption, degradation, diffusion, and mechanics. Various in vitro and in vivo approaches have been used to study buccal drug delivery systems. This paper discusses the mechanisms of action, mucosal adhesion theories, and standard techniques for producing films. Key areas of study in buccal drug delivery systems include evaluating films for weight variation, thickness, folding endurance, surface pH, percentage of moisture absorption and loss, tensile strength, swelling index, content uniformity, and in vitro permeation studies.

Nanotechnology-based mucoadhesive and mucus-penetrating drug-delivery systems for transbuccal drug delivery.

Buccal drug-delivery systems present a promising approach for the drug delivery to the buccal mucosa, addressing oral cavity-specific problems, enabling systemic delivery and minimizing adverse effects on biological systems. Numerous strategies have been proposed to load drug-containing nanoparticles (NPs) to the buccal mucosa for local and systemic applications. There has been considerable interest in the development of mucoadhesive buccal formulations, particularly hydrogel composites utilizing mucoadhesive films incorporating NPs. Drug permeability and controlled drug release through buccal drug delivery continues to pose a challenge despite the availability of various remedies. This review highlights the need for, mechanisms and latest advances in NP-based transbuccal drug delivery with a focus on various pathological disorders and examples and limitations of the different methods.

Formulation and Evaluation of Buccal film of Rabeprazole sodium

Novel drug delivery systems are designed to ensure continuous delivery of drugs in predictable and reproducible kinetics over prolonged time. Buccal drug delivery system localizes the delivery of drug to tissues in the oral cavity for treatment of bacterial and fungal infection as in various periodontal diseases. This study aimed to formulate buccal film of rabeprazole drug with Hibiscus rosasinensis mucilage and Basil leaves extract. It improves therapeutic efficacy, patient compliance and the bioavailability. The present formulation targets oral ulcers that will remain in the application site for a longer period and minimizing the side effects. rabeprazole sodium, Hibiscus rosasinensis mucilage and Basil leaves extract was used for Pharmacological activity and incorporated into the buccal film prepared by solvent casting method. In the present study six formulations of rabeprazole alone and in combination with Hibiscus rosasinensis mucilage and Basil leaves extract were prepared as buccal films, by solvent casting technique. Six The F1–F6 formulations contain rabeprazole sodium, Hibiscus rosasinensis mucilage, Basil leaves HPMC, Polyvinyl alcohol, Sodium alginate, and Propylene glycol and Distilled water. Prepared film was evaluated for different parameter including pH, thickness, weight variation, folding endurance, moisture uptake and moisture content, swellability, drug content, tensile strength, in vitro drug release and stability studies. The Formulation F3was considered as ideal film with maximum release of 98.90%. F3 shows maximum disintegration time of 25 min, tensile strength of 6.98. The drug content of the formulation F3 was found to be 98.47%. The maximum moisture content showed in F4 and minimum in F2. Stability of this film was also monitored for 2 months without having any signs of deterioration, difference in pH, drug content and drug release. This study demonstrates the prospective use of buccal films as a viable and alternative approach for effective delivery of rabeprazole in treatment of Oral ulcers.

A Comprehensive Review on Buccal Drug Delivery System

A Comprehensive Review on Buccal Drug Delivery System

Recent Advancements and Patents on Buccal Drug Delivery Systems: A Comprehensive Review.

The major requirement for a dosage form to be successful is its ability to penetrate the site of application and the bioavailability of the drug released from the dosage form. The buccal drug delivery is an influential route to deliver the drug into the body. Here, in this context, various novel approaches that include lipoidal carriers like ethosomes, transferosomes, niosomes etc. and electrospun nanofibers are discussed, with respect to buccal drug delivery. These carriers can be easily incorporated into buccal dosage forms like patches and gels that are responsible for increased permeation across the buccal epithelium. The in vivo methods of evaluation on animal models are conscribed here. The novel biocarriers of lipoidal and non-lipoidal nature can be utilized by loading the drug into them, which are helpful in preventing drug degradation and other drawbacks as compared to conventional formulations. The globally patented buccal formulations give us a wide context in literature about the patents filed and granted in the recent years. When it comes to patient compliance, age is an issue, which is also solved by the buccal route. The pediatric buccal formulations are researched for the customization to be delivered to children. Diseases like mouth ulcers, oral cancer, Parkinson's disease, aphthous stomatitis etc. have been successfully treated through the buccal route, which infers that the buccal drug delivery system is an effective and emerging area for formulation and development in the field of pharmaceutics.

Buccal drug delivery system

The buccal area of the oral mucosa provides an adorable channel of systemic medication distribution within the mouth mucosa. Drugs are delivered via oral mucosal layer, that has a higher first-pass metabolism and degrades gastrointestinal. The medication is immediately transmitted via the systemic circulation via the buccal drug delivery mechanism, which allows for painless administration, quick enzymatic action, high bioavailability, and reduced liver metabolism. The disadvantages of the oral drug delivery route include substantial presystemic metabolism, which causes medicines to a break down in an acidic environment due to poor absorption. Buccal delivery is an attractive administrative route due to its ease of delivery through the buccal mucosal membrane lining of the oral cavity. This review paper provides a comprehensive overview of the oral mucosa, mucoadhesion, variables influencing the whole process, assessment methodologies, and how to eliminate obstacles when formulating buccal drug delivery formulations.

Hollow mesoporous silica nanoparticles-loaded ion-crosslinked bilayer films with excellent mechanical properties and high bioavailability for buccal delivery

Mucoadhesive buccal films (MBFs) become the most promising buccal mucosal delivery system duo to its advantageous properties, including simple preparation technique and better patient compliance. The mechanical properties and mucoadhesion of MBFs are crucial in their successful performance as well as manufacturing and administration. In this study, we prepared hollow mesoporous silica nanoparticles-loaded ion-crosslinked bilayer films (CCS-PVA-TPP-FSM@HMSNs) using carboxymethyl chitosan (CCS) and polyvinyl alcohol (PVA) for buccal delivery of furosemide (FSM). The FSM-loaded hollow mesoporous silica nanoparticles (FSM@HMSNs) were firstly characterized by SEM, TEM, and nitrogen adsorption/desorption. Then, we constructed an ion-crosslinked network using CCS and PVA employed with the solution casting method, and sodium tripolyphosphate (TPP) was used as a hydrogen bond crosslinking agent. The formulation was optimized through Box-Behnken design, where the impact of the proportion of the ingredients on the quality of the films was evaluated entirely. Herein, folding endurance, swelling, tensile strength, and adhesion force were selected as response variables. Morphology, mechanical, spectroscopic, thermal, and safety of CCS-PVA-TPP-FSM@HMSNs films were also investigated. The release and permeability behaviors of CCS-PVA-TPP-FSM@HMSNs films were evaluated by in vitro drug release, across isolated porcine buccal and TR146 cell model. The CCS-PVA-TPP-FSM@HMSNs films showed outstanding mechanical properties, suitable bioadhesion, high drug loading, significant sustained-release properties, and improved permeability. In pharmacokinetic study with golden hamster models, the relative bioavailability was increased by 191.54%, and the absolute bioavailability was 82.20%. In summary, this study provides evidence that this innovative CCS-PVA-TPP-FSM@HMSNs films could be a promising and industrialized buccal drug delivery system.

Buccal drug delivery system

It is well known that certain medications suffer hepatic first-pass metabolism or deteriorate in the digestive system, the buccal drug delivery method may be an alternative to oral administration. Because it is painless and may be swiftly and readily removed if the treatment must be terminated or interrupted, the buccal mucosa has long been ideal for administering medications. This paper focuses on the buccal drug delivery system had the goal of gathering recent literature and presenting a concise explanation of buccal patches by discussing the characteristics of an ideal mucoadhesive system, benefits of buccal delivery and disadvantages thereof, factors affecting buccal absorption, and various types of patches as well as the preparation method and composition thereof. The compilation of the data is also enhanced by adding market products as well as the patented, so that reader will get the complete knowledge about the buccal drug delivery.

Critical review on buccal mucoadhesive drug delivery systems

Traditional oral dosage forms prone to first pass metabolism and degra­dation due to enzymes but mucoadhesive dosage form able to bypass first pass metabolism and related degradation. It also offers more patient compliance without risk of chocking in case of paediatric and geriatric patients. Buccal mucosa is considered as a convenient and easily accessible site for the drug administration for both local and systemic delivery. Mucoadhesion is a process involving chemical interactions between mucin and polymers. The use of mucoadhesive polymers in buccal drug delivery has gained a great attention. Various mucoadhesive dosage forms, including tablets, patches, disks, wafers, ointments and gels have recently been developed. Amongst them, buccal patches offer greater flexibility and comfort than the other forms. Smart materials such as stimuli-responsive hydrogels, liposome-based patches, polymeric micelles, etc. play a vital role in the development of these drug delivery systems by their efficient carrier capacity, prolonging the residence time of the drug at the site of absorption, improved drug bioavailability, reduced dosing frequency and improved patience compliance.

Formulation and Evaluation of Buccal Disintegrating Tablet of Anticonvulsant Drug

Oral and Buccal delivery is currently the gold standard in the pharmaceutical industry where it is regarded as the safest, most convenient and most economical method of drug delivery having the highest patient compliance. To troubleshoot such problems a new dosage form known as Buccal and orally disintegrating tablet, has been developed which rapidly disintegrate and dissolve in saliva and then easily swallowed without need of water which is a major benefit over than conventional dosage form. In addition, patients suffering from dysphasia, motion sickness, repeated emesis and mental disorders prefer such preparation because they cannot swallow large quantity of water. the immediate release of medication and for instant release at desire location in which the drug is absorbed distributer and easily metabolized. e.g. To prepare and characterize buccal tablets of Gabapentin using different super disintegrants such as Cross povidon, PVP K30, Micro crystalline cellulose. This types of formulation of improving solubility of drug and development of Buccal drug delivery system.

Influence of additives on swelling and mucoadhesion properties of glyceryl monooleate liquid crystals

Liquid crystalline systems of glyceryl monooleate/water are used as drug delivery systems due to their complex structure that controls drug diffusion. Mucoadhesive properties of glyceryl monooleate suggest it can be used for buccal delivery. Using additives is a strategy to modify physical and chemical properties of liquid crystalline systems and optimize their performance as a drug delivery system. However, the presence of additives can significantly alter properties such as phase behavior, swelling and mucoadhesion. Our aim is to investigate the influence of additives on swelling and mucoadhesion of glyceryl monooleate-based liquid crystals, intending them to be used as buccal drug delivery systems. The systems were characterized regarding their mesophases, swelling rate, and mucoadhesion. All the systems studied were able to absorb water and presented mucoadhesion, which is interesting for the development of buccal drug delivery systems. Additives induced phase transitions and affected the swelling performance, while mucoadhesive properties were poorly affected. Propylene glycol increased water uptake, while oleic acid induced the phase transition to the hexagonal phase and reduced the swelling rate. The association of oleic acid (5%) and propylene glycol (10%) resulted in a cubic phase system with strong mucoadhesive properties that can be a potential drug carrier for buccal delivery.

Oromucosal Alginate Films with Zein Nanoparticles as a Novel Delivery System for Digoxin.

Digoxin is a hydrophobic drug used for the treatment of heart failure that possesses a narrow therapeutic index, which raises safety concerns for toxicity. This is of utmost relevance in specific populations, such as the elderly. This study aimed to demonstrate the potential of the sodium alginate films as buccal drug delivery system containing zein nanoparticles incorporated with digoxin to reduce the number of doses, facilitating the administration with a quick onset of action. The film was prepared using the solvent casting method, whereas nanoparticles by the nanoprecipitation method. The nanoparticles incorporated with digoxin (0.25 mg/mL) exhibited a mean size of 87.20 ± 0.88 nm, a polydispersity index of 0.23 ± 0.00, and a zeta potential of 21.23 ± 0.07 mV. Digoxin was successfully encapsulated into zein nanoparticles with an encapsulation efficiency of 91% (±0.00). Films with/without glycerol and with different concentrations of ethanol were produced. The sodium alginate (SA) films with 10% ethanol demonstrated good performance for swelling (maximum of 1474%) and mechanical properties, with a mean tensile strength of 0.40 ± 0.04 MPa and an elongation at break of 27.85% (±0.58), compatible with drug delivery application into the buccal mucosa. The current study suggests that SA films with digoxin-loaded zein nanoparticles can be an effective alternative to the dosage forms available on the market for digoxin administration.

AN ASSESSMENT ON BUCCAL MUCOADHESIVE DRUG DELIVERY SYSTEM

Buccal drug delivery system (BDDS) has won a variety of exposure and traction as it possesses plenty of advantages and benefits as evaluate to different mucosal drug delivery systems. Buccal path for systemic drug delivery, the use of mucoadhesive polymers twill significantly increase the efficacy of many tablets, has been of outstanding interest over the previous couple of decades. This article affords a precise of BDDS mechanisms, consisting of a composition of the oral mucosa, delivery mechanism, numerous forms of BDDS, formulation, assessment and application of BDDS. Additionally, this text affords a precis over the patents, advertised products and destiny factors of BDDS. In this evaluation article, we've got tried to assemble the maximum significant reports (1988 to 2021) of formulation, assessment, application, patents of BDDS. This review will help pharmaceutical researchers to clarify the potential of BDDS to overcome the various existing drug delivery dispute like the efficiency of absorption, permeability and bioavailability of drugs.

An Updated Overview on Mucoadhesive Buccal Drug Delivery System

Among the various routes of drug delivery, the oral route is an attractive site for the delivery of drugs. The main advantages of these formulations are: drug targeting, sustained release, increased permanence time in the buccal mucosa, increased bioavailability, and decreased potential adverse effects and maintains constant blood levels for extended period of time. The buccal cavity was found to be the most suitable and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery. Buccal mucosa has a tremendous availability, which leads to direct access to systemic circulation through the internal jugular vein bypasses the drug from hepatic first pass metabolism. The main disadvantage of this route is Limited absorption area- the total surface area of the membranes of the oral cavity available for drug absorption is 170 cm2 of which ~50 cm2 represents non-keratinized tissues, including buccal membrane, the barrier function of the skin changes from one site to the other and from one person to other person with age and large dose of drug are difficult to be administered. Melt granulation is emerging technique and this technique used to increase the dissolution rate of poorly water-soluble drugs. Tablet molding technique: Tablets produced by the molding technique are easier to scale up for industrial manufacture than lyophilisation technique. Hot melt extrusion of film method: Hot melt extrusion has been used for the manufacture of controlled release matrix tablets, pellets and granules, as well as oral disintegrating films.

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.