BIOADHESIVE DRUG DELIVERY SYSTEMS

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Contents
Intoduction Bioadhesion and Mucoadhesion Mechanisms of bioadhesion Theories of bioadhesion Evaluation of bioadhesive interactions Bioadhesive Polymers Applications of bioadhesive polymers References
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The term bioadhesion refers to either adhesion between two biological materials or adhesion between some biological material (including cells, cellular secretions, mucus, extracellular matrix, and so on) and an artificial substrate (metals, ceramics, polymers, etc.)

In terms of the pharmaceutical industry, bioadhesion generally refers to adhesion between a polymer-based delivery system and soft tissue in the presence of water

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Lower and more efficient doses. shape.Advantages Of BDDS The advantages of using BDDS over traditional dosage forms include The ability to optimize the therapeutic effects of a drug by controlling its release into the body. Flexibility in physical state. size. The ability to stabilize drugs and protect against hydro-Iytic or enzymatic degradation  The ability to mask unpleasant taste or odor 4 . Less frequent dosing. and surface. Better patient compliance.

Bioadhesion and Mucoadhesion Targets of orally administered BDDS ‡ Epithelial cell layer ‡ continuous mucus layer ‡ combination of both Bioadhesion Mucoadhesion 5 .

Mechanisms of Bioadhesion Step 1 : wetting and swelling of polymer to permit intimate contact with biological tissue Step 2 : interpenetration of bioadhesive polymer(BP) chains and entanglement of polymer and mucin chains 6 .

covalent bonds) as well as weaker secondary forces such as ionic bonds.e.Step 3 : Formation of chemical bonds between the entangled chains Chemical bonds can include strong primary bonds (i. and hydrogen bonds. 7 . Van der Waals' interactions..

There are six classical theories adapted from studies on the performance of several materials and polymer-polymer adhesion which explain the phenomenon Electronic theory Adsorption theory Wetting theory Diffusion theory Fracture theory 8 .Theories of Bioadhesion Although the chemical and physical basis of mucoadhesion are not yet well understood.

Electronic Theory Electronic theory is based on the premise that both mucoadhesive and biological materials possess opposing electrical charges. when both materials come into contact. Thus. they transfer electrons leading to the building of a double electronic layer at the interface. where the attractive forces within this electronic double layer determines the mucoadhesive strength (Mathiowitz. 1999). Lehr. 9 .

the mucoadhesive device adheres to the mucus by secondary chemical interactions. hydrogen bonds are the prevalent interfacial forces in polymers containing carboxyl groups. a great number of interactions can result in an intense global adhesion Its most widely accepted theory 10 . For example.Adsorption Theory According to the adsorption theory. Such forces have been considered the most important in the adhesive interaction phenomenon because. electrostatic attraction or hydrophobic interactions. although they are individually weak. such as in van der Waals and hydrogen bonds.

This affinity can be found by using measuring techniques such as the contact angle.Wetting Theory The wetting theory applies to liquid systems which present affinity to the surface in order to spread over it. The contact angle should be equal or close to zero to provide adequate spread ability 11 . The general rule states that the lower the contact angle then the greater the affinity .

2-0. According to the literature.The Diffusion Theory Diffusion theory describes the interpenetration of both polymer and mucin chains to a sufficient depth to create a semi-permanent adhesive bond It is believed that the adhesion force increases with the degree of penetration of the polymer chains. the depth of interpenetration required to produce an efficient bioadhesive bond lies in the range 0. flexibility and nature of the mucoadhesive chains. 12 . This penetration rate depends on the diffusion coefficient. mobility and contact time.5 m.

Fm. The maximum tensile stress (aM) produced during detachment can be determined by dividing the maximum force of detachment.The ract re Theor The most useful theory for studying bioadhesion through tensile experiments has been the fracture theory. by the total surface area (A0) involved in the adhesive interaction: 13 . which analyzes the forces required to separate two surfaces after adhesion.

is it possible to obtain the detachment. Depending on the direction in which the mucoadhesive is separated from the substrate. shear.Methods to Evaluate Bioadhesive Interactions In Vitro Techniques Tests measuring mucoadhesive strength Measuring the force required to break the binding between the model membrane and the mucoadhesive. and rupture tensile strengths (Hägerström. 2003) The force most frequently evaluated in such tests is rupture tensile strength 14 .

2003) or intestinal mucus from rats. which can be a disc composed of mucin (Bruschi et al. 2007).Texture Analyzer Here the force required to remove the formulation from a model membrane is measured. a piece of animal mucous membrane.. 15 . This method is more frequently used to analyze solid systems like microspheres It also evaluates the texture of the formulations and assess other mechanical properties of the system. generally porcine nasal mucus (Hägerström.

contact angle.The Wilhelmy plate technique Its used for dynamic contact-angle measurement and involves a microbalance or tensiometer. The surface tension. A glass slide is coated with the polymer of interest and then dipped into a beaker of synthetic or natural mucus. and adhesive force can be automatically measured using available software 16 .

yielding both contact angle and surface tension. 17 . after contact time. is lowered back to the initial position.Microforce Balance A unique microsphere is attached by a thread to the stationary microbalance. The chamber with the mucous membrane is raised until it comes into contact with the microsphere and.

Shear test The shear test measures the force required to separate two polymer-coated glass slides joined by a thin film of natural or synthetic mucus. The results of this technique often correlate well with in vivo test results 18 .

In Vivo Techniques In vivo measurements of GI bioadhesive performance involve administering BPs to laboratory animals and monitoring their transit rate through the gut. They are orally force-fed by gavage  surgically implanted in the stomach infused with a perfusion pump through an in situ loop of the small intestine monitored transit using radiopaque markers radioactive elements fluorescent labeling techniques 19 .

Bioadhesive Polymers First generation mucoadhesive materials These materials are natural or synthetic hydrophilic molecules containing numerous organic functions that generate hydrogen bonds such as carboxyl. which do not adhere specifically onto several surfaces. These polymers can be subdivided into three classes: ‡Cationic ‡Anionic ‡Nonionic 20 . hydroxyl and amino groups.

chitosan Anionic polymers mucoadhesion results from physical-chemical processes. hydrogen and van der Waals bonds. Nonionic polymers.g. such as hydrophobic interactions. Eg: polyacrylic acid (carbomers) carboxymethylcellulose alginates.Cationic polymers These can interact with the mucus surface. since it is negatively charged at physiological pH.. E. Hydroxypropylmethylcellulose Hydroxyethylcellulose methylcellulose 21 . Eg.

2001) *Ionic concentration sensitive. park.g. Polymethacrylic acid * Light sensitive. e. like hyaluronic acid (qiu.. *Electric signal sensitive e. Polymers linked to concavalin A.g. such as gellan gum (hagerstrom et al. 2000) 22 .g.g. presenting increased viscosity at higher ph values *Glucose sensitive. e. They have ability to gelify in situ after exposure to an external stimulus They can be classified as *Thermosensitive. e. Poloxamers and carbomers *Ph sensitive.Hydrogels Hydrogels are three-dimensional and hydrophilic polymer networks capable of swelling in water or biological fluids and retaining a large amount of fluids in the swollen state. Polyacrylic acid.

‡ Fimbrial proteins (woodley. 2004) ‡ Those obtained by the addition of thiol groups to known molecules 23 . stimulate endocytosis and finally to have a broad safety range ‡Lectins. ‡Antibodies (chowdary. show mucoadhesive properties in its solid and liquid forms. be specific for a particular cellular area or site. inhibit local enzymes or promote absorption. ‡Invasins. 2001). rao.Second generation mucoadhesive materials An ideal polymer should exhibit the ability to incorporate both hydrophilic and lipophilic drugs.

Applications of Bioadhesive Polymers Possible means of administration for BDDSs include occular respiratory buccal nasal GI rectal urethral Vaginal GI bioadhesive devices that can be administered orally are of considerable interest owing to the ease of administration and targeted contact with the absorbing intestinal epithelium 24 .

Common BDDS shapes and forms used in current research efforts have includes Bioadhesive patches (buccal and transdermal) Bioadhesive tablets (buccal. open wounds) Bioadhesive microsperes (GI track) Bioadhesive liposomes 25 . vaginal) Bioadhesive powers (mouth) Bioadhesive gels (eye. gingival. mouth. rectum. vagina.

Mucoadhesive Tablets y Mucoadhesive tablets have been developed to increase the retention of drug in GIT and/or to keep a sustained release of drug towards the medium from where it is constantly removed. y Thus. treatment of many diseases is done. 26 . y The microbeads are made from a hydrogel polymer specifically developed for use as a temporary pre-meal gastric bulking agent. y These mucoadhesive formulations offer many advantages in comparison to traditional treatments against dental and buccal diseases and disturbances.

enhanced bioavailability and effectiveness of drug due to targeted delivery to a specific region of the GI tract 2. improved drug protection by polymer encapsulation and direct contact with absorbing cell layers 4. maximized absorption rate due to intimate contact with the absorbing membrane and decreased diffusion barriers 3.The development of efficient orally delivered BDDSs could enable the following four important effects: 1. longer gut transit time resulting in extended periods for absorption 27 .

Teflon. y Among these substrates. 28 . mercury was found to give best results. glass and aluminium are used for film formation.Mucoadhesive Buccal Films y are most commonly prepared by the solvent casting technique in which various substrates including mercury.

a much more intimate contact with the mucus layer. with diameters in the micrometer range (typically 1 m to 1000 m (1 mm)). have advantages of efficient absorption and enhanced bioavailability of drugs.Mucoadhesive microspheres Microsphere are small spherical particles. 29 . and specific targeting of drugs to the absorption site.

Mucoadhesive microparticles is an improved drug delivery system which are believed to bind to the mucus layer coating the stomach and other regions of the GIT. 30 .1 and 100 m in size. These mucoadhesive microparticles bind to the mucus layer leading either to slow release into the GIT or direct delivery to the gastrointestinal mucosa.Mucoadhesive Microparticles Microparticles are particles between 0.

In a relatively simplistic form.Mucoadhesive Microcapsules Micro-encapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small capsules many useful properties. 31 . Mucoadhesive microcapsules are a type of controlled-release dosage form. a microcapsule is a small sphere with a uniform wall around it. They can be used for vaginal administration to treat vaginal infections and to increase patient convenience. They offer numerous benefits including reducing stress resulting from restraint. handling. Avoiding expensive or difficult drug administration procedures. and dosing .

vol.228 Braz. 2010 32 . Second Edition By Yie W.1 São Paulo Jan. Pharm.46 no. Chien pg./Mar. J. 197 . no. Sci.References Encyclopedia Of Controlled Drug Delivery by Edith Mathiowitz Encyclopedia Of Pharmaceutical Technology Third Edition edited by James Swarbrick pg. 2021 . no .2039 Novel Drug Delivery Systems.

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