Buccal Drug Delivery System Research Articles

Mucoadhesion and Mucopenetration of Cannabidiol (CBD)-Loaded Mesoporous Carrier Systems for Buccal Drug Delivery

Transmucosal drug delivery represents a promising noninvasive option when drugs are employed which have a low oral bioavailability like CBD. However, this concept can only be successful as long as the formulation provides sufficient buccal retention and mucosal penetration. In this study, mucoadhesive carrier systems were evaluated consisting of CBD-loaded silica (Aeroperl 300) carriers, mucoadhesive polymers (Hypromellose (HPMC), chitosan and carbomer) and propylene glycol as a penetration enhancer. Mucoadhesive effect, drug release and penetration ability were evaluated for each carrier system. The results show that the addition of HPMC and carbomer substantially improve mucoadhesion compared to pure CBD, with an increase of 16-fold and 20-fold, respectively. However, due to their strong swelling, HPMC and carbomer hinder the penetration of CBD and rely on co-administration of propylene glycol as an enhancer to achieve sufficient mucosal absorption. Chitosan, on the other hand, achieves an 8-fold increase in mucoadhesion and enhances the amount of CBD absorbed by three times compared to pure CBD. Thus, chitosan represents a promising polymer to combine both effects. Considering the results, the development of silica-based buccal drug delivery systems is a promising approach for the effective delivery of CBD.

Formulation and Characterization of Eplerenone Mucoadhesive Buccal Tablets

Mucoadhesive drug release system is a preferably unidirectional release system where mucosal epithelial exterior is enclosed by the mucus deposit that interacts with the bio-adhesive drug delivery system and swelling time of the buccal dosage form which is amplified by mucin molecules at the location of administration. Eplerenone is an Anti-hypertensive drug that undergoes hepatic first pass metabolism and shows 69% of bioavailability. In order to bypass the hepatic first pass metabolism the drug is designed to be delivered through buccal cavity to avoid the first pass metabolism. Eplerenone buccal tablets were formulated by using direct compression method with different polymers like HPMC K 100M, Carbopol 934P, Carbopol 974P, Xantham Gum, Eudragit L100 and NaCMC in various concentrations and compositions. Incompatibility complications were not observed from the FTIR spectrums. The formulated and prepared buccal solid dosage forms were evaluated for pre-compressions and post- compression parameters such as hardness, weight variation, thickness, friability, surface pH, swelling index, in-vitro dissolution studies, drug content uniformity, mucoadhesion strength and mucoadhesion time. Evaluation results of formulation F12 are proven to be the optimal formulation showing highest mucoadhesion time, mucoadhesion strength and in-vitro drug release for prolonged period of time about 8 hours. Eplerenone is best delivered through buccal drug delivery system to enhance its oral bioavailability and bypass the hepatic first pass metabolism.

A Complete Review on Mucoadhesive Buccal Tablets

Drug actions can be improved by novel drug delivery system, such as mucoadhesive system. Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and prolongs the residence time of the dosage form at the site of application. Bio adhesion may be defined as the state in which two materials, at least one of which is of a biological nature, are held together for extend periods of time by interfacial forces. Buccal mucosa is the preferred site for both systemic and local drug action. The mucosa has a rich blood supply and it relatively permeable. Buccal trans mucosal delivery helps to bypass first- pass metabolism by allowing direct access to the systemic circulation through the internal jugular vein. This article briefly describes. Introduction to mucoadhesive drug delivery system, structure and function of oral mucosal membrane, buccal drug delivery and mucoadhesive property, theories and mechanism of mucoadhesion, mechanism to increase drug delivery through buccal route, buccal drug delivery system formulation design, characterization of buccal tablet, evaluation of buccal tablet.

MUCOADHESIVE BUCCAL FILMS: A NOVEL APPROACH FOR THE DELIVERY OF ANTI-HYPERTENSIVE DRUGS

The buccal drug delivery system is a prominent route of administration for drug delivery through the buccal mucosa. It is rich in blood supply with more surface area for rapid absorption as well as provides direct entry of drugs from the site of application into the systemic circulation through the jugular vein. Buccal drug delivery systems consist of various approaches such as lozenges, wafers, gels, microparticles, patches or films from which mucoadhesive buccal film is an attractive dosage form in terms of flexibility and high systemic bioavailability. Since most of the antihypertensive drugs show first-pass metabolism which leads to less oral bioavailability generally up to 20–50%. Thus, incorporation of antihypertensive drugs in mucoadhesive buccal films using mucoadhesive polymers can provide higher systemic bioavailability. The films can be formulated using various techniques such as solvent casting method and hot extrusion melt method. These films can be evaluated based on various characteristics to determine their efficacy and performance such as tensile strength, mucoadhesion residence time, and kinetic release data analysis. They have various advantages over conventional solid oral dosage forms, hence are preferable for the preparation of antihypertensive drug-loaded buccal films. Mucoadhesive buccal films of antihypertensive drugs can also provide controlled drug delivery with enhanced bioavailability.

Current Status of Mucoadhesive Gel Systems for Buccal Drug Delivery.

Buccal drug delivery is a fascinating research field. Gel-based formulations present potent characteristics as buccal systems since they have great physicochemical properties. Among the various gels, in situ gels are viscous colloidal systems consisting of polymers; when physiological conditions change (pH, temperature, ion activation), they are transformed into the gel phase. These systems can improve bioavailability. Other systems, such as nanogels or emulgels can also be applied for buccal delivery with promising results. Polymeric gel-based systems can be produced by natural, semisynthetic, and synthetic polymers. Their main advantage is that the active molecules can be released in a sustained and controllable manner. Several gels based on chitosan are produced for the entrapment of drugs demonstrating efficient retention time and bioavailability due to chitosan mucoadhesion. Besides polysaccharides, poloxamers and carbopol are also used in buccal gels due to their high swelling ability and reversed thermal gelation behavior. Herein, the authors focused on the current development of mucoadhesive gel systems used in buccal drug delivery. After explaining buccal drug delivery and mucoadhesion, various studies with hydrogels, in situ gels, and nanogels were analyzed as buccal gel systems. Various mucoadhesive gel studies with mucoadhesive polymers have been studied and summarized. This review is presented as valuable guidance to scientists in formulating buccal mucoadhesive drug delivery systems. This review aimed to assist researchers working on buccal drug delivery by summarizing buccal drug delivery, mucoadhesion, and buccal mucoadhesive gel systems recently found in the literature.

Mucoadhesive properties of polyacrylates: Structure – Function relationship

The objective of this study was to evaluate and compare the mucoadhesive properties of ten commercially available polyacrylates including linear polyacrylic acid of 100 and 450 kDa (PAA 100 and 450), with allyl pentaerythritol, allyl sucrose and divinyl glycol cross-linked PAAs (PAA AP, PAA AS/AP, PAA DG) as well as hydrophobically modified cross-linked PAAs (PAA C10-30). Swelling behavior, rheological measurements of polymer/mucus mixtures, rotating cylinder studies and tensile studies were performed to evaluate the mucoadhesive properties of PAAs on intestinal, vaginal and buccal mucosa. Investigations on the swelling behavior revealed that higher degree of cross-linking of PAA and higher degree of alkylation of acrylates/C10-30 alkyl acrylate crosspolymers cause a more pronounced swelling following the rank order: PAA C10-30 high > PAA C10-30 medium > PAA C10-30 low > PAA AP high > PAA AP low > PAA AS/AP > PAA DG > PAA C10-30 very low > PAA 450 > PAA 100. The rank order of dynamic viscosity of polymer/mucus mixtures was PAA C10-30 medium > PAA C10-30 low > PAA C10-30 very low > PAA AP high > PAA C10-30 high > PAA AS/AP > PAA DG > PAA AP low > PAA 450 > PAA 100. Rotating cylinder studies and tensile studies showed that mucoadhesive properties of all tested polymers depended on the type of porcine mucosa and the simulated biological buffer. The experiments on various mucosae showed the highest mucoadhesion of PAA AP high, PAA C10-30 low and PAA C10-30 medium. In contrast, the weakest mucoadhesion was attributed to linear PAA 100 and 450 and PAA C10-30 very low. Within this study, the mucoadhesive properties of ten different types of polyacrylates were compared with each other facilitating the decision-making for formulation scientists when developing oral, buccal or vaginal mucoadhesive drug delivery systems.

Emerging Role of Hydrogels in Drug Delivery Systems, Tissue Engineering and Wound Management.

The popularity of hydrogels as biomaterials lies in their tunable physical properties, ability to encapsulate small molecules and macromolecular drugs, water holding capacity, flexibility, and controllable degradability. Functionalization strategies to overcome the deficiencies of conventional hydrogels and expand the role of advanced hydrogels such as DNA hydrogels are extensively discussed in this review. Different types of cross-linking techniques, materials utilized, procedures, advantages, and disadvantages covering hydrogels are tabulated. The application of hydrogels, particularly in buccal, oral, vaginal, and transdermal drug delivery systems, are described. The review also focuses on composite hydrogels with enhanced properties that are being developed to meet the diverse demand of wound dressing materials. The unique advantages of hydrogel nanoparticles in targeted and intracellular delivery of various therapeutic agents are explained. Furthermore, different types of hydrogel-based materials utilized for tissue engineering applications and fabrication of contact lens are discussed. The article also provides an overview of selected examples of commercial products launched particularly in the area of oral and ocular drug delivery systems and wound dressing materials. Hydrogels can be prepared with a wide variety of properties, achieving biostable, bioresorbable, and biodegradable polymer matrices, whose mechanical properties and degree of swelling are tailored with a specific application. These unique features give them a promising future in the fields of drug delivery systems and applied biomedicine.

Fluconazole-loaded solid lipid nanoparticles (SLNs) as a potential carrier for buccal drug delivery of oral candidiasis treatment using the Box-Behnken design

The purpose of the present examination was to prepare fluconazole (FZ)-loaded solid lipid nanoparticles (FZ-loaded SLNs) for a buccal drug delivery system using the Box-Behnken design. The FZ-loaded SLNs were prepared using hot homogenization via an ultrasonic probe. The solid lipid, stabilizer, and active ingredient were glyceryl monostearate (GMS) (X1), Tween 80® (X2), and FZ (X3), respectively. The particle size of the FZ-loaded SLNs was in the nano-range of 32.86–269.3 nm. The polydispersity index (PDI) showed a relatively narrow size distribution and was in the range of 0.254–0.495. The zeta potential of all formulations was negatively charged and ranged from −19.8 to −36.9 mV. The entrapment efficiency (%EE) was 56.69–85.49%. Transmission electron microscopy confirmed that the FZ-loaded SLNs were in the nano-range and were spherical. The absence of FZ's melting peak in differential scanning calorimetry thermograms of the FZ-loaded SLNs indicated that the drug had been wholly incorporated into the lipid matrix and had changed from crystalline to amorphous form. The absence of FZ's characteristic peaks in the FZ-loaded SLNs in the Fourier transform infrared spectra confirmed the complete incorporation of FZ in the SLN lipid matrix. The maximum of the determination coefficient (R2) of the Higuchi model was much higher than that of the other models, suggesting that the FZ's kinetic release profile was diffusion-controlled. Permeation studies using porcine buccal mucosa were performed, and at 12 h, the drug could be detected in the buccal tissue, including that in the receptor chamber. The in vitro antifungal activity of the selected FZ-loaded SLNs was studied against Candida albicans, and all selected FZ-loaded SLNs showed inhibition zones, indicating that the FZ from the FZ-loaded SLNs had an antifungal effect. Therefore, FZ-loaded SLNs is a promising drug delivery carrier for local and systemic treatment of candidiasis through the buccal mucosa.

An analytical assessment on Mucoadhesive Buccal Drug Delivery System for improving patient convenience and compliance

In recent years, the novel mucoadhesive buccal drug delivery system has been developed over the conventional and systemic dosage forms. To bypass drugs from the hepatic first-pass metabolism and it enhances the bioavailability of drug at the site of administration. Absorption of a drug through the buccal mucosa reduces the degradation. Some of the enzyme activity and pH variation in the gastrointestinal tract reduces the absorption and active drug loss. To overcome this problem, the buccal route is preferred. Polymers are used in this formulation to improve the drug release rate over an extended period, and also, the therapeutic plasma level of the drug can be rapidly achieved. Overall this narrative review explains mechanism and theories, method of preparation, factors affecting mucoadhesion, advantages and limitations, applications, components used in the formulation, characterization and evaluation methods. Since the cytoplasm and intercellular spaces are hydrophilic. Lipophilic drugs have a low solubility in this environment. However, the cell membrane is rather lipophilic; it tends to difficulty permeating the hydrophilic solute through the cell membrane because of a low partition coefficient. Therefore, the cytoplasm and intercellular spaces act as a major barrier to penetration of lipophilic compounds and the cell membrane poses as an extensive transport barrier for hydrophilic compounds. Since the oral epithelial is stratified, the permeation of solute may involve these combination routes so that the route is more predictable.

MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEMS CONTAINING POLYSACCHARIDES

The buccal mucosa is an attractive site for drug administration as it allows avoiding the enzymatic degradation of the drug in the gastrointestinal tract and its hepatic metabolism. For buccal administration, different drug delivery systems with controlled mucoadhesion have been developed and some of them are available on the market. Mucoadhesion makes it possible to obtain prolonged, local or systemic drug action, and this process is highly influenced by several factors, among which, the reactivity of macromolecules from the formulations is very important. Polysaccharides are increasingly studied due to their abundance in natural resources, low-cost availability and easy chemical modification, but also due to their biocompatibility, biodegradability and non-toxicity properties. This review briefly describes the advantages of using the buccal route of drug administration, the influencing factors that are taken into account for obtaining mucoadhesive dosage forms, and the main polysaccharides and their derivatives used for fabrication of buccal drug delivery systems.

Rospective designing and types of buccal drug delivery system: The Review

Buccal bioadhesive films, releasing topical drugs in the oral cavity at a slow and predetermined rate, provide distinct advantages over traditional dosage forms for treatment of many diseases. The mucosa of the buccal cavity is the most easily accessible transmucosal site. This fast dissolving drug delivery system (FDDS) is suited for the drugs which undergo high first pass metabolism and is used for improving bioavailability with reducing dosing frequency to mouth plasma peak levels, which in turn minimize adverse/side effects and also make it cost effective This article aims to review the recent Designs of buccal patches and their developments in the buccal adhesive drug delivery systems, & Buccal drug delivery is a promising area for continued research with the aim of systemic delivery of orally inefficient drugs as well as a feasible and attractive alternative for non-invasive delivery of potent peptide and protein drug molecules.

Rospective designing and types of buccal drug delivery system: The Review

Rospective designing and types of buccal drug delivery system: The Review

Recent Developments and Potential of Mucoadhesive Buccal Drug Delivery System for Oro-mucosal Disorders

Background: The drug delivery across buccal mucosa is a very interesting option for the treatment of various oro-mucosal disorders such as aphthous stomatitis, periodontitis, gingivitis, toothache, periodontitis, and sjorgensen syndrome. But it is quite difficult because of target site movements, limited area for drug absorption, drinking of fluids, intake of food and saliva flow at regular intervals, contributing to poor retention and sub-therapeutic level of drug at the target site. Due to this, the mucoadhesive buccal drug delivery system has gained a great deal of attention among the various scientists and researchers over the last two decades. Methods: Mucoadhesion is a process of attachment between the natural or synthetic macromolecule and mucosal epithelial surface with the aid of interfacial attractive forces. The process of mucoadhesion has been extensively encouraged by the utilization of mucoadhesive polymers within the formulation that on contact with salivary fluid swells and adheres to buccal epithelium membrane, thus prolonging the drug release, retention time and improving therapeutic performance in case of oral diseases. The present review tries to cover the basic anatomy and structure of oral mucosa, pathways of drug absorption, the theory of mucoadhesion, mechanisms involved in mucoadhesion and various factors affecting mucoadhesion. Results: It highlights the properties of mucoadhesive polymers in drug delivery along with various dosage forms such as mucoadhesive tablets, films, patches, gels, and pastes. Furthermore, it also sheds light on the recent developments made in the field of mucoadhesive buccal drug delivery system that reflects the potential of this system for the effective treatment of oro-mucosal disorders. Conclusion: It can be concluded that the mucoadhesive buccal drug delivery system has great potential in the near future for treating oro-mucosal disorders.

Interpolymer Complexes Based on Eudragit<sup>®</sup> EPO/Eudragit<sup>®</sup> S100 as Carriers for Oral Controlled Drug Delivery Systems

Introduction. The possibility of obtaining IPC based on polyanions of various structures Eudragit ® , Carbopol ® , pectin, carrageenan and sodium alginate with oppositely charged polycations - Eudragit ® EPO, Eudragit ® RS/RL and chitosan, stabilized as already well-known by ionic bonds. It has been proven that interpolymer complexes with the participation of Eudragit ® copolymers could be also formatted by hydrogen bonds too as well. Prepared polycomplexes are promising carriers for drug delivery systems (DDS) to various parts of the gastrointestinal tract (GIT): the mouth (orodispersible and buccal DDS), stomach (gastroretentive DDS) and intestine (colon-specific DDS). Aim. Study of interpolymer complexes based on a pair of Eudragit ® EPO and Eudragit ® S100 copolymers obtained in a medium of various organic solvents (ethyl alcohol and a mixture of isopropanol-acetone (in a ratio of 60:40, v/v) from the point of view of their use in oral matrix systems for the delivery of active pharmaceutical ingredients. Materials and methods. The synthesis of interpolymer complexes based on Eudragit ® copolymers was carried out in organic solvents [ethyl alcohol or isopropanol-acetone mixture (in a ratio of 60:40, v/v)]. The structural features of the obtained IPCs were assessed by FTIR spectroscopy using a Nicolet iS5 instrument with a Smart iTR single ATR attachment (Thermo Scientific, USA) and differential scanning calorimetry with modulated temperature (mDSC) using a Discovery™ DSC instrument (TA Instruments, USA). The composition was determined using the method of elemental analysis on a Thermo Flash 2000 CHNS/O device (Thermo Fisher Scientific, UK). The swelling capacity of the obtained IPCs was evaluated in buffer media with pH values that mimic the pH of different parts of the gastrointestinal tract (GIT): 1.2; 5.8; 6.8 and 7.4. The release of theophylline (TEO) and diclofenac sodium (DS) was assessed on a ERWEKA DFZ II (ERWEKA GmbH, Germany) flow through cell apparatus in buffer media simulating the pH of various parts of the gastrointestinal tract for 7 hours. Results and discussion . All obtained IPCs are characterized by an excess of Eudragit ® S100 in their composition. The obtained IPCs are stabilized by a cooperative system of ionic and hydrogen bonds. DSC thermograms of IPC samples are characterized by the presence of a single glass transition temperature, which confirms the absence of impurities of free copolymers in their composition, while with an increase in the content of Eudragit ® S100 in the IPC composition, the glass transition temperature increases. The matrix based on IPC-1 disintegrated during the first 15 minutes of the experiment in a medium with pH 1.2, while matrices based on the rest of the IPC samples retain their shape for 7 hours and are characterized by pH-independent behavior. The release of TEO from polycomplex matrices is diffusion-controlled and occurs in accordance with Fick's law (IPC-2, IPC-4, and IPC-6) or can be characterized as «abnormal transport» (IPC-1, IPC-3 and IPC- 5), and also depends on the swelling capacity of the matrix. In contrast, the release of DS is dependent on surface erosion of the matrix, which is consistent with the Super Case II transport mechanism. Conclusion. The resulting interpolymer complexes Eudragit ® EPO/Eudragit ® S100 are promising carriers in matrix oral systems for the controlled delivery of active pharmaceutical ingredients, providing a prolonged release of BCS class I substances, depending on the diffusion rate from the swollen matrix, and a delayed release of BCS class II substances, controlled by surface processes erosion of the matrix.

Impact of the mucoadhesive lyophilized wafer loaded with novel carvedilol nano-spanlastics on biochemical markers in the heart of spontaneously hypertensive rat models.

The purpose of this investigation was to encapsulate carvedilol, a model beta-blocker antihypertensive into nano-spanlastics, followed by incorporation into 1% CMC wafer to afford a mucoadhesive buccal drug delivery system, targeting to sidestep the first-pass metabolism, improving the drug absorption and pharmacological effect, achieving non-invasive buccal delivery for treating hypertension. Carvedilol-loaded nano-spanlastics were rendered by ethanol injection technique, using 23 factorial design. The effect of formulation variables was investigated on nano-spanlastic characteristics. The optimal nano-spanlastic formulation (S2; containing 20% Brij 97) exhibited particle size (239.8 ± 5nm), entrapment efficiency (98. 16 ± 1.44%), deformability index (8.74 ± 0.42g), and the flux after 24h (Jmax) (22.5 ± 0.25 (μg/cm2/h) with enhancement ratio 2.87 as well as excellent stability after storage. Permeation study verified the preeminence of the S2 formula. A confocal laser scanning microscope showed deep penetration of S2 through sheep buccal mucosa formula compared to rhodamine B solution. S2-based wafer showed acceptable characters (pH, swelling, drug content, residence time, and release rate). In vivo studies (pharmacodynamic study and biochemical evaluation) showed considerable improvement in blood pressure, the profile of the lipid, oxidant stress biomarkers, and cardiac markers. Histopathological studies revealed the superiority of S2 wafer in the protection of heart tissues over Carvid®. The results achieved indicate that nano-spanlastic-based wafer offers a promising improving trans-buccal carvedilol delivery system. Graphical abstract.

Terahertz optical and mechanical properties of the gelatin-starch-glycerol-bentonite biopolymers

With the fast development of terahertz technology in medical diagnosis and monitoring, it has become important to investigate the application of THz radiation in the cancer treatment assessment during the therapy. In this paper, a buccal drug delivery system is studied as the first step towards this application. The drug delivery system is based on a gelatin-starch biopolymer matrix filled with plasticizing glycerol and various contents of reinforcing particles of bentonite clay. The biopolymers were subjected to morphology analysis using optical microscopy, analysis of mechanical tensile properties, and analysis of terahertz optical properties, followed by a theoretical approach of the experiment. The results show a visible effect of the bentonite content on both of the mechanical and terahertz optical properties of the biopolymer. These findings allow us to confirm the feasibility of using THz radiation for cancer assessment during therapies. The proposed biopolymer also has the potential to be applied as a substrate when carrying out in-vivo optical property measurement of biotissue in terahertz frequency range.

An Overview on Various Approaches and Recent Patents on Buccal Drug Delivery Systems.

Buccal delivery is an alluring course of organization for fundamental medication conveyance and it leads direct access to the systemic flow through the interior jugular vein sidesteps drugs from the hepatic first-pass digestion gives high bioavailability. This article aims at buccal medication conveyance by discussing the structure and condition of the oral mucosa and the novel strategies utilized in evaluating buccal medication ingestion. This review highlights the various pharmaceutical approaches for buccal delivery such as buccal tablets, buccal lozenges, buccal micro/nanoparticle, wafer and semisolid dosage forms like chewing gums, buccal patch, buccal gel or ointment and some buccal liquid dosage forms like buccal solutions and buccal sprays and recent patents filed or granted for these approaches. Recently, some patents are also reported where a combination of various approaches is being employed to achieve very effective mucosal delivery. The various patent search sites were used to collect and analyze the information on buccal drug delivery systems. The present study provides valuable information, advantages, limitations and future outlook of various buccal drug delivery systems.

PHYSICOCHEMICAL CHARACTERIZATION OF PROPRANOLOL-LOADED CHITOSAN NANOPARTICLES FOR A BUCCAL DRUG DELIVERY SYSTEM

Objective: This study aimed to characterize the physicochemical properties, including pH, zeta potential, and particle size of propranolol-loaded nanoparticles that were incorporated into a buccal transmucosal drug-delivery system.
 Methods: An ionotropic gelation technique was used to formulate propranolol-loaded chitosan nanoparticles. Chitosan used as the nanoparticle base, using tripolyphosphate (TPP) as a cross-linking agent. The effects on nanoparticle physical properties, including pH, zeta potential, and particle size were examined when various chitosan [0.150-0.300 % (w/v)] and propranolol contents (0-40 mg) were used during the preparation. The effects of using chitosan solutions with different pH values on nanoparticle properties were also determined.
 Results: The pH values of all nanoparticles ranged between 4.14–4.55. The zeta potentials of the prepared nanoparticles ranged between 22.6–52.6 mV, with positive charges. The nanoparticle sizes ranged from 107–140 nm, which are within the range of suitable particle sizes for transmucosal preparations.
 Conclusion: The pH values, zeta potentials, and particle sizes of the nanoparticle formulations were influenced by the concentrations of chitosan and propranolol and by the pH of the initial chitosan solution. The relationships between nanoparticle properties and all factors primarily depended on the ionic charges of the components, especially chitosan. Our study provides beneficial physicochemical knowledge for the further development of chitosan-based nanoparticles containing propranolol for buccal drug delivery systems.

Polycomplex Carrier for Buccal Mucoadhesion Delivery of Metronidazole

Introduction. One of the well-known requirements for buccal drug delivery systems is the demonstration of mucoadhesive properties of the carrier, ensuring retention on the mucosa for a long time with the gradual release of the included drug. It should be noted that one of the advantages of buccal systems compared with oral ones is the absence of the «first pass effect» through the liver.Aim. To carry out a physicochemical and pharmaceutical research of the interpolyelectrolyte complex (IPEC), obtained on the basis of pharmaceutically acceptable polymers – Eudragit® EPO and Noveon® AA-1, in comparison with the physical mixture and individual polymers, as a mucoadhesive delivery system of metronidazole for the treatment of periodontal diseases.Materials and methods. Obtained on the basis of a pair of pharmaceutical polymers (Eudragit® EPO and Noveon® AA-1), two IPEC samples were characterized by elemental analysis, FTIR spectroscopy, and modulated temperature differential scanning calorimetry (mDSC) in comparison with individual polymers and their physical mixtures. The study of swelling ability, bioadhesion and release was carried out in a medium simulating artificial salivary fluid (pH 7.0) at a temperature of 37 ± 0.1 °C. Mucoadhesion of polymer samples and IPEC was studied using a TA.XTplus texture analyzer (Stable Micro Systems, UK). The release of metronidazole (MD) from matrices based on the developed IPEC was studied on a CE 7Smart USP 4 apparatus (Sotax, Switzerland) using the Flow Trough Cell method at a speed a flow of 20 ml/min in an open cycle within 5 hours. The amount of released MD was estimated by UV spectrophotometry on a Lambda 25 instrument (PerkinElmer, USA) at a wavelength of 319 nm.Results and discussion. As a result of studies on the physicochemical and pharmaceutical properties, there was selected the optimal composition of a polycomplex carrier (IPEC 2) based on Eudragit® EPO and Noveon® AA-1, which is characterized by the required bioadhesive properties and the ability of providing controlled release of drug from the tablet matrix (with weight ratio MD/IPEC-2 1:0.5) in conditions mimicking oral cavity environment, which provides the necessary mode of buccal delivery of metronidazole in accordance with Fick's law of diffusion.Conclusion. IPEC 2 is a perspective for use as carrier for buccal controlled delivery of metronidazole.

Biopolymer Substrates in Buccal Drug Delivery: Current Status and Future Trend.

This paper provides a critical review of biopolymer-based substrates, especially the cellulose derivatives, for their application in buccal drug delivery. Drug delivery to the buccal mucous has the benefits of immobile muscle, abundant vascularization and rapid recovery, but not all the drugs can be administered through the buccal mucosa (e.g., macromolecular drugs), due to the low bioavailability caused by their large molecular size. This shortfall inspired the rapid development of drug-compounding technologies and the corresponding usage of biopolymer substrates. Cellulose derivatives have been extensively developed for drug manufacturing to facilitate its delivery. We engaged in structured research of cellulose-based drug compounding technologies. We summarized the characteristic cellulose derivatives which have been used as the biocompatible substrates in buccal delivery systems. The discussion of potential use of the rapidly-developed nanocellulose (NC) is also notable in this paper. Seventy-eight papers were referenced in this perspective paper with the majority (sixty-five) published later than 2010. Forty-seven papers defined the buccal drug delivery systems and their substrates. Fifteen papers outlined the properties and applications of cellulose derivatives. Nanocellulose was introduced as a leading edge of nanomaterial with sixteen papers highlighted its adaptability in drug compounding for buccal delivery. The findings of this perspective paper proposed the potential use of cellulose derivatives, the typical kind of biopolymers, in the buccal drug delivery system for promoting the bioavailability of macromolecular drugs. Nanocellulose (NC) in particular was proposed as an innovative bio-binder/carrier for the controlled-release of drugs in buccal system.