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PRACTICE SCHOOL “MUCOADHESIVE DRUG DELIVERY SYSTEM: AN OVERVIEW OF MECHANISM, MATERIALS AND RECENT ADVANCES” Submitted in partial fulfilment of the requirement for the Degree of Bachelor of Pharmacy (VII Semester) the Faculty of Science and Technology, Sant Gadge Baba Amravati University, Amravati. Submitted By Ms. Radhika S. Chaudhari Guide Ms. N. S. Gallani M. Pharm Institute of Pharmacy & Research, Anjangaon Bari Road, Badnera Amravati. 2024 – 2025.

Prof. (Dr.) S. J. Dighade M. Pharm., Ph.D., Principal, Institute of Pharmacy & Research, Anjangaon Bari Road, Badnera-Amravati. CERTIFICATE This is to certify that the Practice School Project entitled, “MUCOADHESIVE DRUG DELIVERY SYSTEM: AN OVERVIEW OF MECHANISM, MATERIALS AND RECENT ADVANCES” submitted in respect to the subject Practice School of seventh semester for bachelor degree course in the faculty of Science and Technology, Sant Gadge Baba Amravati University, Amravati. This project work has been carried out at Institute of Pharmacy & Research, Badnera - Amravati by Ms. Radhika S. Chaudhari under guidance and supervision of Ms. N. S. Gallani, Assistant Professor, Institute of Pharmacy & Research, Badnera - Amravati. This practice school project work is now ready for examination. Place: Badnera Prof. (Dr.) S. J. Dighade Date: Principal.

DECLARATION I hereby declare that the Practice School Project entitled, “MUCOADHESIVE DRUG DELIVERY SYSTEM: AN OVERVIEW OF MECHANISM, MATERIALS AND RECENT ADVANCES” is based on work carried out in the Institute of Pharmacy & Research, Badnera - Amravati. The Practice school project is now ready for examination. Place: Badnera Date: Ms. Radhika S. Chaudhari.

Acknowledgment Emotion cannot be adequately expressed in words because then, emotions are transformed into more formalities. My acknowledgements are many times more than what I am expressing here but the formalities have to be completed. I express my sincere thanks to respected Prof. (Dr.) S. J. Dighade, Principal, IOPR, Badnera for providing me enthusiastic academic environment and all necessary facilities required for Project work. I feel immense pleasure to acknowledge my profound sincere, sense of gratitude for valuable guidance, keep interest of encouragement right from selection of practice topic up to final shaping of the Project towards my guide N. S. Gallani, Assistant Professor, IOPR Badnera. It is privilege to work under his able and inspiring guidance. I therefore feel indebted to him. I am also thankful to my friends, Ms. Tanaya P. Bhoyar, Mr. Anurag N. Dhale, Mr. Om R. Chakule, Ms. Rutuja J. Chavhan for supporting me, directly or indirectly during any difficulty and problems during my project work. Last one but not the least I wish to express my hearty thanks to my parents, who always encouraged me at every moment of my life to move ahead and make one’s own position in the society on your own. I shall remain thankful to them forever. Place: Badnera Date: Ms. Radhika S. Chaudhari.

Ms. N. S. Gallani, M.Pharm. Assistant Professor, Institute of Pharmacy & Research, Anjangaon Bari Road, Badnera-Amravati. CERTIFICATE This is to certify that the Practice School Project entitled, “MUCOADHESIVE DRUG DELIVERY SYSTEM: AN OVERVIEW OF MECHANISM, MATERIALS AND RECENT ADVANCES” submitted in respect to the subject Practice School of seventh semester for bachelor degree course in the faculty of Science and Technology, Sant Gadge Baba Amravati University, Amravati. This project work has been carried out at Institute of Pharmacy & Research, Badnera-Amravati by Ms. Radhika S. Chaudhari under my guidance and supervision. This practice school project work is now ready for examination. Place: Badnera Ms. N. S. Gallani Date: Guide.

INDEX Sr. No. Contents Page. No. 1. Introduction 1 2. Advantages And Disadvantages Of Mucoadhesive Drug Delivery System 3 3. Theories Of Mucoadhesion 4 4. Mechanism Of Mucoadhesion 8 5. Muco-Adhesive Polymer 10 6. Factor Affecting Mucoadhesive Drug Delivery System 12 7. Routes Of Administration For Mucoadhesive-Based Drug Delivery System 14 8. Evaluation Tests For Mucoadhesive Drug Delivery Systems 23 9. Recent Advances In Mucoadhesive Drug Delivery System 28 10. Conclusion 33 11. Reference 34.

LIST OF FIGURES Fig. No. Name of Figure Page. No. 1. Schematic Representation of Approaches to Oral Mucoadhesive Drug Delivery System 2 2. The Classification of Theories of Mucoadhesion as Per Physical and Chemically 4 3. Show Pentration of Dosage Form into the Surface of Tissue of the Mucosal Layer by Wetting or Swelling Mechanism 5 4. Indicates the Stages Concerned with Mucoadhesion 6 5. Adhesion Between the Mucus Membrane(Negative Charge) and the Polymeric System (Positive Charge) Through Differences in their Electronic Structure 6 6. Fracture Occuring for Mucoadhesion 7 7. The Structural Representation of Mucoadhesion Mechanism 9 8. Classification of Mucoadhesive Polymer 10 9. Factor Affecting Mucoadhesion 13 10. Oral Drug Delivery System 15 11. Nasal Drug Delivery System 17 12. Ocular Drug Delivery System 18 13. Vaginal Drug Delivery System 19 14. Rectal Drug Delivery System 21 15. Different Forces Evaluated in Mucoadhesive Tablet 23 16. Schematic Diagram of Falling Liquid Film Method 24 17. Fluorescent Probe Equipment 25 18. Diagram of Colloidal Gold Staining Technique 26 19. Adhesion Test 27 20. Administration of Buccal Tablet 28.

LIST OF TABLES 21. Medicated Chewing Gum 29 22. Vaginal Formulation in Mucoadhesive Gel 30 23. Mucoadhesive Buccal Film 31 24. Mucoadhesive Buccal Patches 32 Table No. Name of Table Page. No. 1. Composition of Acid Buffering Bioadhesive Vaginal Tablet 20 2. Different Types of Mucoadhesive Dosage Form 22.

LIST OF ABBREVIATIONS Sr. No. Abbreviations Full Form 1. PVA Polyvinyl Alcohol 2. PLGA Poly(Lactic-co-glycolic acid) 3. PEG Polyethylene Glycol 4. SM Maximum Stress Of Detachment.

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 1 1. INTRODUCTION The link created by coming into touch with a pressure-sensitive adhesive and a surface is known as adhesion. This idea started to be used in relation to drug delivery systems in the 1980s. Interest in pharmaceutical technology has grown significantly as a result of the mucoadhesion idea, it is the condition in which two surfaces are held together by interfacial forces, which may include valence forces, interlocking action, or both, according to the American Society of Testing and Materials [1]. Mucoadhesive drug delivery techniques extend the dosage form's stay in residence at the application or absorption site. They make it easier for the dosage form to make intimate touch with the underlying absorption surface, which enhances the drug's therapeutic effectiveness. Enhancing its bioavailability and fostering local or systemic effects as a result [2]. Such mucoadhesive drug delivery systems for oral, buccal, nasal, rectal, and vaginal routes have been developed recently for both systemic and local effects. Mucoadhesive systems have the potential to be used as drug carriers since they prolong the time spent at the absorption site and enable closer contact with the epithelial barrier. On the other side, the mucociliary clearance system has the potential to hinder the adhesion of preparations to mucosal membranes [3]. The preparation may also be eliminated by this clearance, which serves as the body's natural defence against the deposition of impurities onto the mucous membrane. Consequently, it is possible to direct the drug to a particular site or tissue and keep the preparation at the site of action by using bioadhesive molecules [4]. Reduced drug administration frequency and improved adherence to therapy are two additional benefits of the creation of controlled drug delivery systems using bioadhesive molecules. In order to maintain an effective concentration of the drug at the action site, a bioadhesive system controlling drug release could therefore enhance the treatment of diseases [5]. The term "mucoadhesive" is widely used to describe adhesive systems used on mucous membranes, however the meanings are interchangeable. Since the characteristics of adhesion depend heavily on the characteristics of the material used in its creation, it is possible to create a bio (muco) adhesive system in various dosage forms. Although research on the mechanisms underlying mucoadhesion.

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 2 has advanced over the past twenty years, along with the creation of new mucoadhesive systems and polymers, mucoadhesion is still not completely understood [6]. Figure No. 01: Schematic Representation of Approaches to Oral Mucoadhesive Drug Delivery System. MUCOADHESION The term bio-adhesion can be defined as the state in which two materials, at least one biological in nature, are held together for an extended period of time by interfacial forces. In biological systems, bio-adhesion can be classified into 3 types: Type1, adhesion between two biological phases, for example, platelet aggregation and wound healing. Type 2, adhesion of a biological phase to an artificial substrate, for example, cell adhesion to culture dishes and bio-film formation on prosthetic devices and inserts. Type 3, adhesion of an artificial material to a biological substrate, for example, adhesion of synthetic hydro gels to soft tissues and adhesion of sealants to dental enamel..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 3 1.1 ADVANTAGES OF MUCOADHESIVE DRUG DELIVERY SYSTEM  Improved Bioavailability: Drug delivery through the mucosa bypasses the first-pass hepatic metabolism and the gastrointestinal tract itself, thus enhancing bioavailability.  Rapid absorption of drugs: Mucous membranes have ready access to the blood stream so that substances can be rapidly absorbed from them.  Controlled drug delivery: Drug delivery systems might be designed for mucous membranes, which can deliver a drug over a period of time in sustained or controlled manner.  Non-invasive: Mucosal drug delivery is a non-invasive method.  Patient compliance: Mucosal drug delivery systems may enhance patient compliance. 1.2 DISADVANTAGES OF MUCOADHESIVE DRUG DELIVERY SYSTEM  Low dose: Mucoadhesive drug delivery systems cannot provide high levels of drugs.  Patient acceptance: Patients may not find the taste acceptable or might consider the formulation irritating. In that case, they need to limit or completely withhold their food and liquids.  Swallowing: Such formulation can be swallowed by the patient.  Drugs with special nature: Bitter-tasting drugs or those with an unpleasant smell cannot be administered, so also drugs that are an irritant to the mucous membranes.  Absorption: The surface area that is available for absorption is limited.  Dissolution: Saliva flows constantly and can dissolve the medication.  Ulcerous effects: Drugs which are ulcerogenic in nature may produce local ulcerous effects if they stay for a long time in contact with the mucosa.  Transmucosal permeability: The absorption of drugs through the oral mucosa varies. Hence, it is not used to administer low potent drugs.  Mucociliary clearance: Mucociliary clearance may become problematic.  Nasal irritation: Irritation of the nasal pathway may pose a problem..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 4  Formulation problems: There may be formulation problem [7]. 1.3 THEORIES OF MUCOADHESION Figure No. 02: The Classification of Theories of Mucoadhesion as Per Physical and Chemically. I. WETTING THEORY The wetting theory is generally applied in mucoadhesive system (liquid) having low viscosity. The theory postulates about the mucoadhesive polymer ability that easily spreads on biological surface which leads to the extensively spreading ability of active drug delivery systems. This theory describes that the adhesive constituent penetrates in irregularities in surface which hardens and get attached to the surfaces because of drastic changes occurs in surfaces and interfacial energies [8]. The adhesive mechanism of such elastoviscous liquid may be defined by using wettability and spreadability as shown in (fig. 3)..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 5 The contact angle techniques are based on the principle that lowers the contact angle, these are used to determine the affinity of a liquid to measure contact angle of the liquid on the surface. The theory postulates that the lower the contact angle, the greater will be the affinity of liquid to the solid surface [9]. Figure No. 03: Shows Penetration of Dosage Form into the Surface or Tissue of the Mucosal Layer by Wetting or Swelling Mechanism. II. ADSORPTION THEORY Vandar waals' forces and hydrogen bonds, two types of chemical bonds for adhesive interactions, are deeply ingrained between the adhesive polymer and mucus substrate, as shown in Adhesion is defined as the result of interactions in various surfaces (primary and secondary). While secondary bonds are primarily produced by Vander Waals forces, hydrophobic interactions, and hydrogen bonding, primary bonds are caused by chemisorptions, which lead to adhesion due to ionic, covalent, and metallic bonding [10]. First stage shows the interaction of drug delivery system on the surface of mucus membrane; Second stage shows several physicochemical interactions, results in prolonged adhesion at the site of action as shown in (fig 4)..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 6 Figure No. 04: Indicates the Stages Concerned with Mucoadhesion. III. ELECTRONIC THEORY According to this theory, adhesion is caused by an exchange of electrons between the mucus and the mucoadhesive system, which results from differences in their electronic structures. As shown in (fig. 5), the mucus and mucoadhesive system interface forms a bi-layer of electronic charges as a result of the electron transfer between the mucus and the mucoadhesion [11, 12]. This theory is founded on the idea that biological and mucoadhesive materials both have polarised electrical charges. Thus, electrons are transferred when the two materials come into touch, creating a double electrical layer at the interface. The formation of attractive forces within this double layer is the end result of such a process [13]. Figure No. 05: Adhesion between the mucus membrane (negative charge) and the polymeric system (positive charge), through differences in their electronic structure..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 7 IV. FRACTURE THEORY This is perhaps the most used theory in studies on the mechanical measurement of mucoadhesion. It analyses the force required to separate two surfaces after adhesion is established. This force, sm, is frequently calculated in tests of resistance to rupture by the ratio of the maximal detachment force, Fm, and the total surface area, A0, involved in the adhesive interaction [14]. Sm=F/A Where, Sm = Maximum stress of detachment. F = Maximum force of detachment. A = Unit area from which detachment occurred. Figure No. 06: Fractures Occurring for Mucoadhesion..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 8 1.4. MECHANISMS OF MUCOADHESION The mechanism of adhesion of certain macromolecules to the surface of a mucous tissue is not well understood yet. The mucoadhesive must spread over the substrate to initiate close contact and increase surface contact, promoting the diffusion of its chains within the mucus. The 1st stage is characterized by the contact between the mucoadhesive and the mucus membrane, with spreading and swelling of the formulation, initiating its deep contact with the mucus layer. In spite of the extensive research in this field, the mechanisms of mucoadhesion are not completely clear. However, it is agreed upon that mucoadhesion takes place in two steps [15]. A] THE CONTACT STAGE The mucoadhesive and make intimate contact with each other in this step. The mucosal membrane and mucoadhesive first make an intimate touch. Because the mucosal surface of the digestive tract inaccessible, the adhesive substance cannot be applied directly to the surface or delivered to it by organ design. For the most part, adhesion and it might be harmful if the gastrointestinal tract becomes blocked, when it is considered that the mucus gel surface of adhesion rather than a solid, and that the particles may in-vivo become hydrated and coated with biomolecules, drastically altering their physicochemical characteristics, the issue becomes more problematic. B] THE CONSOLIDATION STAGES A variety of physicochemical interactions take place in this stage to strengthen and stabilise the adhesive junction, resulting in a longer adherence. It is suggested that a second "consolidation" stage is necessary to establish strong or persistent adhesion. A change in the mucus layer's physical characteristics is necessary to achieve strong adhesion; otherwise, it won't be able to hold on to the bioadhesive polymer when dislodging stress is applied, therefore this process is explained by two theories. The later theory explains why mucoadhesion occurs in a matter of seconds, while the former requires the polymers to interpenetrate several micrometer distances within a short time..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 9 The rheological studies suggest that interpenetration of mucus and mucoadhesive polymer leads to formation of a surface gel layer, which will substantially inhibit any further interpenetration [16]. Figure No. 07: The Structural Representation of Mucoadhesion Mechanism..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 10 1.5. MUCO-ADHESIVE POLYMERS Mucoadhesive delivery systems are under consideration for localization of the active agents to a particular location/site. Polymers have been of prime importance in designing such systems so as to increase the residence time of the active agent at the desired location. Polymers used in the mucosal delivery system may be of either natural or synthetic origin. In this section, we will briefly discuss some of the common classes of mucoadhesive polymers. Figure No. 08: Classification of Mucoadhesive Polymer. These muco-adhesive polymers can be divided into two broad categories: 1. Natural Polymers: a. Chitosan: Chitosan is a polymer derived from chitin, which is the exoskeleton of crustaceans. It is a widely used mucoadhesive polymer because it is biocompatible and has a barrier-forming capacity that improves drug absorption. It can be used in oral, nasal, and ocular drug delivery systems. b. Hyaluronic Acid: A natural polymer used in terms of connective tissues or the extracellular matrix to be used in ophthalmic drug delivery to be used for enhancing drug retention on the ocular surface..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 11 c. Alginate: Alginate is an algal polysaccharide. It is taken from brown algae. The most important application of this polysaccharide is as a component in buccal drug delivery systems where it forms gels that can sustain the release of drugs. 2. Synthetic Polymers: a. Polyvinyl Alcohol (PVA): PVA is a synthetic, water-soluble polymer used in Ocular drug delivery. It can be formulated into eye drops or contact lenses to improve the bioavailability and retention of drugs. b. Poly (lactic-co-glycolic acid) (PLGA): PLGA is a synthetic biodegradable and biocompatible polymer used as a major formulation of the drug delivery of microparticles or nanoparticles, particularly through mucosal administration. The drug delivery process from these allows for a sustained release as well as controlled kinetics release. c. Polyethylene Glycol (PEG): PEG is a synthetic polymer that improves drug solubility and stability in various mucosal drug delivery systems, such as nasal and ocular formulations [17]..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 12 1.6 FACTOR AFFECTING MUCOADHESIVE DRUG DELIVERY SYSTEM A] POLYMER BASED FACTORS 1. Molecular weight: Many researchers have proved that strong bio adhesion is strictly a function of the specific molecular weight for optimum molecular weight, according to the nature of bioadhesive polymer used in application [18]. 2. Flexibility: When polymer chains diffuse at the interfacial region, \bio-adhesion is attained. Therefore for the required interaction with a mucous \membrane, this polymer should also be flexible [19]. 3. Hydrogen bonding capacity: it is proved that excellent Hydrogen bonding is indispensable for Mucoadhesion, and the flexibility of the polymer should be of paramount importance to enhance this ability [20]. 4. Cross-linking ability: The rate of increase in crosslink density reduces the diffusion of water into the polymer network and, thus reduces appropriately, \polymer swelling followed by a rate of interpenetration between the polymer and mucin, hence reducing Mucoadhesion rate [21]. 5. Charge: Nonionic polymers are of lower degree adhesion in comparison with anionic polymers. Some of the cationic polymers,such as chitosan, exhibit superior adherence, particularly in slightly alkaline or neutral environments [22]. 6. Polymer concentration: a low concentration of polymer may result in an unstable contact between polymer and mucin; in general, a more concentrated polymer will result in longer penetration chain length and improved Mucoadhesion [23]. 7. Hydration or swelling: polymer swelling is governed by the ionic strength, polymer concentration and cross-linking density, plus the presence of water. Over hydration results in wet slippery mucilage formation that prevent adhesion [24]..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 13 B] ENVIRONMENTAL AND PHYSIOLOGICAL FACTORS 1. PH: the site of application pH affects the charge that the mucus surface has except for certain ionizable polymers. The degree of hydration of different polymers (such as polyacrylic acid) is susceptible to the pH of the environment [25]. 2. Contact time at the commencement: the extent of swelling interpenetration of polymer chains is a product of the contact time that bio adhesive polymer and mucus layer. In addition, when the initial contact time becomes higher, the strength of the bio-adhesive increases [26]. 3. Mucin turn over: time of the bioadhesive in contact with the site for administration depends upon the solubility of the polymer in water and the rate of turnover of mucin [27]. 4. Diseased state: In different disease states, secretion of mucus from the mucus membrane is reduced, for instance dry Mouth Syndrome. Accordingly, at the time of attachment, there is lesser amount of mucus present that is unable to interact with the bio adhesive polymer [28]. Figure No. 09: Factors Affecting Mucoadhesion..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 14 1.7 ROUTES OF ADMINISTRATION FOR MUCOADHESIVE – BASED DRUG DELIVERY SYSTEM The wet tissue that borders the mouth, gut, nose, eye lids, rectum and genital region is known as the mucosa or the mucus membrane. Table 2 lists the different mucus membrane structures according to where on the body they are located. Past formulations of mucoadhesive drug delivery methods included powders, compacts, sprays, semisolids, and films [29]. For instance, powders and nanoparticles have been employed to enhance medication administration to the nasal mucosa, while compacts have been used for drug delivery to the oral cavity, for the tongue or buccal cavities have recently been created. Table 3 provides information on the mucoadhesive dose forms [30]. Alternative delivery system concepts have recently attracted more attention. It has been hypothesised that buccal films might provide more comfort and flexibility than sticky tablets. Additionally, films could solve the issue of oral gels' relatively limited residence period [31]. The production of bioadhesive films uses cellulose derivatives, poly (acrylic acids) like Carbopol, poly (methylvinylether/maleic anhydride), and Gantrez copolymers, among other film-forming bioadhesive polymers [32]. 1. ORAL MUCOADHESIVE DRUG DELIVERY SYSTEMS: Due to its easy accessibility, drug administration through the oral mucosa has attracted a lot of research. The most often utilised rotes are thought to be the buccal and sublingual routes. A relatively permeable barrier to drug transport is provided by the nonkeratinized epithelium in the oral cavity, which includes the soft palate, the mouth floor, the ventral side of the tongue, and the buccal mucosa [33]. Paracellular transport is followed by hydrophilic substances and big or highly polar molecules, while transcellular transport through the lipid bilayer is followed by lipophilic substances,Drug delivery via the oral mucosa has been particularly effective and offers a number of benefits over other drug.

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 15 delivery methods, such as avoiding hepatic first-pass metabolism, increasing drug bioavailability, improving patient compliance, having excellent accessibility, unidirectional drug flux, and having improved barrier permeability when compared , for instance, to intact skin[34]. Local and systemic medication distribution has taken place in the mouth cavity. Disease conditions like aphthous ulceration gingivitis, periodontal disease, and xerostoma are treated with local drug therapy. Adhesive gels, tablets, films, patches, ointments, mouthwashes, and pastes are a few different dosage forms [35]. Figure No. 10: Oral Drug Delivery System. Adhesive tablets have traditionally been the widely utilised dosage form for buccal medication distribution. Tablets can be placed on the cheeks, lips, gums, and palate, among other areas of the oral cavity. Buccal pills, in contrast to traditional tablets, allow speaking, eating, and drinking without experiencing any significant discomfort. Perioli investigated how mucoadhesive buccal tablet behaviour and medication release rate were affected by compression force. Hydroxyethyl cellulose.

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 16 and carbopol 940 were used in a 1:1 ratio as matrix-forming polymers to create tablets under various compression forces [36]. Water penetration and polymer chain stretching were not significantly impacted by compression pressures, but mucoadhesion performance and medication release were. While improving in vivo mucoadhesive and hydration time, increased compression force reduced drug release both in vitro and in vivo. Furthermore, it was found that tablets made with the least amount of force produced the best results as opposed to tablets made with the most amount of force, which produced pain during in vivo application and required human volunteers to detach them [37]. Despite many clinical research, mucosal medication administration via the buccal route is still highly difficult. Here, we highlight a number of formulations that are either commercial goods or are undergoing clinical testing. The 3M Company has created a buccal patch system that consists of a backing material and a matrix patch containing a drug, mucoadhesive polymers, and polymeric elastomers. Their buprenorphine patch has been reported to provide good patient comfort and can deliver the medication for up to 12 hours [38]. 2. NASAL MUCOADHESIVE DRUG DELIVERY SYSTEMS: The nasal cavity is an intriguing structure due to the normal human nasal mucosa's size of 150 cm, it’s extremely dense circulatory network, and its somewhat permeable membrane structure. The presence of proteolytic enzymes, the mucociliary clearance of 5 minutes, and the effect of pathological states are drawbacks (cold and allergies). Rapid uptake and avoiding firstpass hepatic metabolism are two benefits. Additionally, applying liquids, semisolids, and solids with a bioadhesive can significantly lengthen retention time [39]. The short residence period at this mucosal surface might limit the nasal administration of therapeutic proteins and peptides. Some bioadhesive polymers may increase protein absorption across the nasal mucosa and prolong residence duration. One problem with nasal administration is the rapid clearance from the nasal cavity through mucociliary clearance with a clearance half-life of around 15 min for solutions. Mucoadhesion, which permits prolongation of retention time, is thus often considered as an essential requirement for efficient nasal administration. Mucoadhesive polymers have been of.

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 17 interest to pharmaceutical scientists for the past few decades because of their application in nasal drug delivery systems, which intend to enhance dosage form residence time in the nasal cavity and improve intimacy of contact awith the absorptive membranes of the biological system. Figure No. 11: Nasal Drug Delivery System. Moreover, the increased paracellular absorption after swelling of the mucoadhesive polymers on the nasal membranes offers an important pathway for the Trans nasal absorption of the macromolecules. It was demonstrated that low drug absorption could be overcome by using absorption enhancers or by prolongation of drug residence time in the nasal cavity, and that some of the mucoadhesive polymers may fulfill both functions [40]. 3. OCULAR MUCOADHESIVE DRUG DELIVERY SYSTEMS: Drug administration to the eye is a challenge because there are several mechanisms (tear production, tear flow, and blinking) that protect the eye from the harmful agents. Conventional delivery methods are not ideal. Solutions and suspensions are readily washed from the cornea and ointments alter the tear refractive index and blur vision; so it is a target to prolong the residence time by mucoadhesion. [41].Many chronic disorders that affect the ocular surface can be treated, and gene transfer is seen to be a potential approach. The author came to the conclusion that when nanoparticles were applied.

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 18 topically to rabbits, they entered the corneal and conjunctival epithelial cells and were assimilated by the cells [42]. Many clinical studies have been performed on mucoadhesive ocular dosage forms. Ocular films applied behind the eye lid were found to prolong retention time and precision of dosing. However, films were found to have a tendency to move across the surface of the eye, thus resulting in irritation, for example, from Ocusert (Alza). It has been shown that the addition of mucoadhesive polymers to ocular films reduced film movement across the eye, minimizing ocular irritation and burning sensations [43]. Figure No. 12: Ocular Drug Delivery System..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 19 4. VAGINAL MUCOADHESIVE DRUG DELIVERY SYSTEMS: A fibro-vascular tube called the vagina connects the uterus to the skin's surface. The stratified squamous epithelium and lamina propia make up the vaginal epithelium. All of the dosage forms for the vaginal route have a brief residence duration, including solutions, gels, suspensions, suppositories, creams, and tablets. Bio-adhesives can increase the residence time of vaginal formulations and regulate the rate of drug release from them. These formulations could either include medication or just work in conjunction with moisturizing agents to treat vaginal dryness [44]. Figure No. 13: Vaginal Drug Delivery System. Recent advances in polymeric technology have increased the potential of vaginal gels. Vaginal gels are semisolid polymeric matrices comprising small amounts of solid, dispersed in relatively large amounts of liquid and have been used in systems for microbicides, contraceptives, labour inducers, and other substances, Various clinical trials of contraceptive gels are also ongoing, with a view to determine their effectiveness. Buffer Gel is in phases II and III clinical trial comparing it to the Gynol II marketed product [45]..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 20 Alam created an acid-buffering bio-adhesive vaginal tablet formulation of the antifungal clotrimazole and the antibiotic metronidazole to treat genitourinary tract infections. It was discovered via bioadhesion experiments and release investigations that sodium carboxymethyl cellulose and polycarbophil were an excellent combination for an acid buffering bio-adhesive vaginal tablet. According to studies on ex vivo retention, the bioadhesive polymers kept the tablet in the vagina for more than 24 hours. The developed tablet's cumulative release profile was compared to that of a commercially available conventional tablet [46]. Pharmaceutical Ingredients Qty. In Mg/Tablet PH Metronidazole 500 - Clotrimazole 100 - Spores Of Lactobacillus Acidophilus 25 - Polycarbophil 36 - Sodium CMC 36 4.4 Microcrystalline Cellulose 282 - Sodium Monocitrate 125 - Sodium Bicarbonate 30 - Ac-Di-Sol 60 - Mg-Stearate 6 - Table No. 01: Composition of Acid Buffering Bio-adhesive Vaginal Tablets..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 21 5. RECTAL MUCOADHESIVE DRUG DELIVERY SYSTEMS: The rectum, which is a component of the colon, has a surface area of 300 cm2 and measures 10 cm in length. The rectum's primary function is the removal of water. It has a very modest surface area for medication absorption due to the absence of villi. The lipid barrier is simply penetrated by a simple diffusion mechanism to achieve the majority of rectal medication absorption. When administered to the rectal area, medications that are subject to severe first-pass metabolism can benefit greatly, especially if they are directed toward regions near the anus. Additionally, the migration distance in the rectum reduced with the addition of bioadhesive polymer [47]. The AUC of flurbiprofen following rectal administration of the liquid suppository containing HP- betaCD demonstrated excellent bioavailability since it did not differ significantly from that following intravenous administration of Lipfen. The scientists came to the conclusion that HP-betaCD would be a better solubility enhancer for the creation of liquid suppositories containing medications that aren't very water-soluble [48]. Figure No. 14: Rectal Drug Delivery System..

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 22 Table No. 02: Different Types of Mucoadhesive Dosage Form. Delivery Dosage forms Routes Tablet Ointment Gel Patch Film Buccal Theophylline Polymers Multiple Benzylnicotinate Polymers Multiple benzydamine, Chitosan Derivatives Miconazole, Pva/Pvp Fentanyl, Pvp Nasal N/A Mupirocin, Glycerin Ester Insulin, Starch Insulin, Chitosan/Peg Chlorpromazin E, Chitosan/ Pectin Ocular Diclofenac Acid Poly(Acrylic) Sulphadicramide, MultiplePolymers Puerarin, Poloxamer/ Carbopol Ciprofloxacin, Pva/Cmc Fluorescein, Hpmc Vaginal Metronidazole, Chitosan Terameprocol, White Petroleum Amphotericin, Pluronic Ala, Pmve/Ma Sds, Multiple Polymers Rectal Ramosetron, Carbopol Zinc-Oxide, Petroleum Quinine, Hpmc N/A Theophylline, Phema.

Mucoadhesive Drug Delivery System: An Overview of Mechanism, Materials and Recent Advances INSTITUTE OF PHARMACY AND RESEARCH, BADNERA, AMRAVATI Page 23 2. EVALUATION TESTS FOR MUCOADHESIVE A] METHODS FOR MUCOADHESIVE STRENGTH MEASUREMENTS I. DETERMINING TENSILE STRENGTH The tensile and shear experiments distribute stress uniformly across the adhesive joint. The peel strength, on the other hand, focuses stress on the edges of the joint. This, however, does not seem correct as stress concentration is always present. The mechanical properties are thus analyzed via tensile and shear tests and peel strength test analyses peeling force. A texture profile analyzer is an example of a technique that is involved in the measurement of the force required to remove bio adhesive films from cut out tissues in vitro. Cut out pieces of the animal’s mucous membrane were utilized for the experiment to assess the force needed to isolate the formulation from a mucin disc model membrane. During the tensile test, the texture analyzer was connected to a slide platform that was also employed to measure peel strength. A bio adhesive film was placed on top of the animal skin held on a platform. Different forces, including the peel strength, were applied at the film to assess the strengths of the peel [49-50]. The figure below depicts various forces, including detachment strength and shear strength. Figure No. 15: Different Forces Evaluated in Mucoadhesive Tablet..