MUCOSAL DRUG DELIVERY SYSTEM

ABSTRACT: The process of mucoadhesion involving a polymeric drug delivery system is a complex one that includes processes such as wetting, adsorption and interpenetration of polymer chains. The success and degree of mucoadhesion bonding is influenced by various polymer-based properties such as the degree of crosslinking, chain length and the presence of various functional groupings. The attractiveness of mucosaltargeted controlled drug delivery of active pharmaceutical ingredients, has led formulation scientists to evaluate numerous polymeric systems for such tasks. Formulation scientists have at their disposal a range of in vitro and in vivo mucoadhesion testing setups in order to select candidate adhesive drug delivery system. As such, mucoadhesive systems have found wide use throughout many mucosal covered organelles for active ingredients delivery for local or systemic effect. Evolution of such mucoadhesive formulations has transgressed from first-generation charged hydrophilic polymer networks to more specific second-generation systems based on lectin, thiol and various other adhesive functional groups. KEYWORDS: Mucoadhesive drugs, mucoadhesive polymers, mucoadhesive routes, Evaluation.                                                                     INTRODUCTION :The concept of mucoadhesion was introduced in the field of controlled release drug delivery systems in the early 1980s1,2 • Buccal /oral route . Thereafter, several researchers have focused on the investigations of the interfacial phenomena of mucoadhesive hydro gels with the mucus. For drug delivery purpose, the term bioadhesion implies attachment of a drug carrier system to a specific biological location. The biological surface can be epithelial tissue. If adhesive attachment is to a mucus coat, the phenomenon is referred to as mucoadhesion. Hence a bacterial attachment is to tissue surfaces, and mucoadhesion can be modeled after the adherence of mucus on epithelial tissue. Mucoadhesion is the relatively new and emerging concept in drug delivery. Mucoadhesion keeps the delivery system adhering to the mucus membrane. By this definition, the mucosal routes for drug delivery are: • Nasal route • Ocular route • Vaginal route • Gastrointestinal route NEED OF MUCOADHESIVE DELIVERY As compared to oral controlled release systems, mucoadhesive delivery system have several advantages by virtue of prolongation of residence time, drug targeting, intimate contact between dosage form and the absorptive mucosa. In addition, mucoadhesive dosage forms have been used to target local disorders at the mucosal surface to reduce dose and to minimize the side effects. Mucoadhesive formulations use polymers as the adhesive component. These polymers are often water soluble and when used in a dry form, they attract water from the mucosal surface and this water transfer leads to a strong interaction further increasing the retention time over the mucosal surfaces and leads to adhesive interactions. Prolonged contact time of a drug with a body tissue through the use of a bioadhesive polymer can significantly improve the performance of many drugs2 . MECHANISM OF MUCOADHESION The mechanism of mucoadhesion between hydrogels and mucosa can be described in three steps. 1. Wetting and swelling 2. Interpenetration of the bioadhesive polymer 3. Formation of weak chemical bonds3 . MUCOADHESIVE POLYMERS Properties 1. It must be loaded substantially by the active compound. 2. Swell in the aqueous biological environment of the delivery–absorption site. 3. Interact with mucus or its components for adequate adhesion. 4. When swelled they allow, controlled release of the active compound. 5. Be excreted unaltered or biologically degraded to inactive, non-toxic oligomers. 6. Sufficient quantities of hydrogen bonding chemical groups. 7. Possess high molecular weight.8.Possess high chain flexibility. 9. Surface tension that will induce spreading into mucous layer.                                                                                                                                                                                                                                                                                                         Mucoadhesive polymer are classified as follows: First generation polymer: Anionic polymer: poly(-acrylic acid), carbopol, polycarbophil, Cationic polymer: Chitosan Second generation polymer: Lecitins, bacterial adhesion New generation polymer: Thiomers POLYMER PROPERTIES DESIRABLE FOR MUCOADHESION Functional group The mucoadhesive polymer possessing hydrophilic functional group such as COOH, OH, NH2, and SO4H may be more favourable in formulating targeted drug delivery system. The functionalized polymer interact with mucus not only through physical entanglement but also through chemical bonds, resulting in formation of cross linked network. Example: Urea is well accepted hydrogen bonding disruptor which decreases mucoadhesiveness of mucin/pectin samples5,6. Degree of hydration Hydration is essential for the relaxation and interpenetration of polymer chains. Excess of hydration could lead to decreased mucoadhesion and/or retention due to the formation of a slippery mucilage. In this situation cross-linked polymers that only permit a certain degree of hydration may be advantageous for providing a prolonged mucoadhesive effect7,8,9. Chain length Chain length and its flexibility is critical for interpenetration and entanglement with the mucus gel. Increased chain mobility leads to increased inter diffusion and interpenetration of the polymer within the mucus network. Long polymer chains lose their ability to diffuse and interpenetrate through mucosal surfaces. Hence as the chain length decreases interpenetration increases10,11. Degree of cross linking The chain mobility and resistance to dissolution is significantly influenced by the degree of cross-linking within a polymer system. Cross-linked hydrophilic polymers swell in the presence of water allowing them to retain their structure. High molecular weight linear hydrophilic polymers are swellable and readily dispersible. Cross-link density increases, chain mobility decreases and hence the effective chain length, decreases, reducing mucoadhesive strength12. Polymer concentration Polymer concentration is dependent on physical state of the delivery system, with differences between semisolid and solid-state dosage form. In the semisolid state, polymer concentration is low which reduces adhesion. Hence lower number of polymer chains are available for interpenetration with mucus. On the other hand, solid dosage forms such as buccal tablets exhibit increased adhesive strength as the mucoadhesive polymer concentration increases13. COMMON SITES OF APPLICATION FOR MUCOADHESIVE DRUG DELIVERY PLATFORM Mucoadhesive formulations have been widely used for their targeted and controlled release delivery to many mucosal membrane-based organelles. Such formulations may deliver active ingredient for local or systemic effect, while bioavailability limiting effects such as enzymatic or hepatic degradation can be avoided or minimised.