Mucosal or Mucoadhesive Drug Delivery System (MDDS).pptx

Mucosal or Mucoadhesive Drug Delivery System (MDDS).pptx

1. Topic: Mucoadhesive Drug Delivery System (MDDS) Presented by Hariom Jaiswal Asst. Pro. B.PH 4 th Year/ 7 th Sam NDDS Rajiv Gandhi College of Pharmacy Nautanwa , Maharajganj UP 273164

2. INTRODUCTION OF MDDS Since the early 1980, the concept of Muco-adhesion has gained considerable interest in pharmaceutical technology. Combine mucoadhesive with enzyme inhibitory & penetration enhancer properties & improve the patient compliance. MDDS have been developed for buccal, nasal, rectal & vaginal routes for both systemic & local effects. Hydrophilic high mol. wt. such as peptides that cannot be administered & poor absorption, then MDDS is best choice.

3. DEFINEIATION OF MDDS "Mucoadhesive drug delivery system are the system which utilizes the property of bio-adhesion of certain polymers which became adhesive on hydration and can be used for targeting a drug to a particular region of the body for prolonged period of time".. Mucoadhesive drug delivery system is a part of controlled delivery system. Mucoadhesive drug delivery system interact with the mucus layer covering the mucosal epithelial surface and increase the residence time of the dosage form at the site of absorption. Examples- Fentanyl, Miconazole, Insulin, Pilogel etc.

4. POLYMER USED IN PREPARTION OF MDDS Natural Mucoadhesive Polymers Gelatine Chitosan Sodium Alginate Pectin Guar gum etc. Synthetic Mucoadhesive Polymers Hydroxypropyl methylcellulose (HPMC) Polyvinyl alcohol (PVA) Polyvinylpyrrolidone (PVP) Polycarbophil etc

5. WHAT IS MUCUS ? Mucoadhesiveinner layers called mucosa inner epithelial cell lining is covered with viscoelastic fluid Composed of water and mucin. Thickness varies from 40 µm to 300 µm Note- Mucin is a high molecular weight glycoprotein secreted by epithelial tissues that lubricates, protects, and maintains the moisture of mucosal surfaces. General composition of mucus Water- 95% Glycoproteins and lipids - 0.5-5% Mineral salts.- 1% Free proteins- 0.5-1%

6. Mucoadhesive drug delivery systems can be delivered by various routes:- Buccal delivery system Oral delivery system Vaginal delivery system Rectal delivery system Nasal delivery system Ocular delivery system

7. BIOADHESION: The term ' bioadhesion ' is commonly defined as adhesion between two materials where at least one of the material is of biological origin. OR ' Bioadhesive ' can be defined as a material that is capable of interacting with biological material and being retained on them or holding them together for extended period of time.

8. NEED OF MDDS MDDS prolong the residence time of the dosage form at the site of application or absorption. Intimate contact of the dosage form with the underlying absorption. Improve the therapeutic performance of drug. Should not cause cause irritation. High drug loading capacity. Controlled drug release(preferably unidirectional release).

9. MARIT & DEMARIT OF MDDS Marits: A prolonged residence time at the site of drug action or absorption. A localization of drug at a given target site. An increase in the drug concentration gradient due to the intense contact of particles with the mucosa A direct contact with intestinal cells that is the first step before particle absorption Ease of administration Termination of therapy is easy. Permits localization of drug to the oral cavity for a prolonged period of time Can be administered to unconscious patients. {except gastrointestinal}

10. Systemic absorption is rapid Less dosing frequency Shorter treatment period Increased safety margin of high potency drugs due to better control of plasma levels Demerits Small mucosal surface for contact. Lack of flexibility of dosage forms. Difficult to achieve high drug release rates required for some drugs. Extent and frequency of attachment may cause local irritation. Patient acceptability in terms to taste and irritancy. Eating and Drinking is prohibited.

11. PRINCIPLES OF BIOADHESION/MUCOADHESION, CONCEPTS: Theories of Bio adhesion: 1. Electronic Theory 2. The wetting theory 3. The adsorption Theory 4. The diffusion Theory 5. The mechanical theory 6. The cohesive theory

12. Electronic Theory Proposes transfer of electrons amongst the surfaces due to difference in their electrical structure resulting in the formation of an electrical double layer there by giving rise to attractive forces. 2. The wetting Theory The wetting theory applies to liquid systems which present affinity to the surface in order to spread over it. This affinity can be measured by contact angle. The general rule states that lower contact angle then greater the affinity.

13. 3. The Adsorption Theory "It is a surface force where surface molecules of adhesive and adherent are in contact. " Bioadhesive systems adhers to tissue due to bond formation i.e covalent bond, ionic bonds, hydrogen bonds,etc . 4. The Diffusion Theory It describes the interpenetration of both the polymer and mucin chains to a sufficient depth to create a semi permanent adhesive bond. The adhesion force increases with the degree of penetration of polymer chains.

14. 5. The Mechanical Theory Mechanical theory considers adhesion due to the filling of the irregularities on a rough surface by a mucoadhesive liquid. 6. Cohesive Theory Proposes that the phenomena of bioadhesion are mainly due to the intermolecular interactions amongst like molecules.

15. MECHANISM OF MUCOADHESION Wetting and swelling of Polymer Interpenetration between the polymer chains and the mucosal membranes Formation of bonds between the entangled chains

16. Step- 1 Wetting and swelling step occurs when polymer spreads over the surface of the mucosal membrane to develop intimate contact. Swelling of the polymer occur because the components of the polymer have an affinity for water. Step- 2 The surface of mucosal membranes are composed of glycoproteins In this step the mucoadhesive polymer chain and the mucosal chains intermingles and entangles to form adhesive bonds. Strength of the bond depends upon the degree of penetration of the two polymer groups. In order to form strong adhesive bonds, one polymer group must be soluble in the Step 3 This step involves formation of weak chemical bonds between entagled polymer chains. This type of bonding formed between the chains include bonds such as hydrogen bonds.

17. TRANSMUCOSAL PERMEABILITY Transmucosal permeability refers to the transport of material such as drugs across the oral mucosa. Transmucosal permeability is a unique approach that aims at delivering the drug systemically through the oral mucosa. As an alternative to enteral delivery of drugs, this route of drug delivery is less invasive. It doesn't require much technical equipment. Thus, making it unsuitable for delivering low potent drugs. Note- Permeability is the measure of a drug's ability to pass through a biological barrier, such as the epithelial layer of a mucosal membrane, to reach the underlying tissue or the bloodstream

18. TRANSMUCOSAL PERMEABILITY: METHODS FOR DRUG ABSORPTION Drugs traverse through the oral mucosa by different methods of absorption. Some of the commonly adopted routes are: Passive diffusion –In this ionic diffusion of drugs from the high concentration to the lower concentration and is the major absorption process. Facilitated diffusion - This is similar to passive diffusion but differs because it uses integral transmembrane proteins to facilitate the transport. Active transport - This transport requires energy for the drug's movement across the oral mucosa. The hydrolysis of ATP often provides the energy. Pinocytosis - In this type of transport, the entire drug molecule is engulfed into the cell as a small vesicle. This process also requires energy in the form of ATP.

19. FACTORS AFFECTING TRANSMUCOSAL PERMEABILITY Lipophilicity of the drug – The permeability is higher for agents or drugs that are highly lipid-soluble. Salivary secretion – Higher the salivary secretion, the higher the drug's chances of being flushed out. This can lead to incomplete absorption of the drug. 3. The saliva's pH - Absorption is favored when the pH is around 6. Binding to the oral mucosa – Proper binding of the drug carrier to the oral mucosa is essential. It helps permeates the drug across the mucosa to the systemic circulation. Oral epithelium thickness – The permeation rate of the drug from the drug carrier is dependent on the thickness of the oral epithelium. The thicker this layer, the longer the residence time of the drug.

20. FORMULATION CONSIDERATIONS OF THE BUCCAL DELIVERY SYSTEMS Buccal delivery systems refer to the administration of the drugs via the buccal mucosa. The buccal mucosa is the mucosa that lines the inner cheek. Formulations targeting this region are placed in the mouth between the upper gums and the cheek. This mucosa is highly vascularized and is relatively easy to access. The absorption of drugs in this region mainly occurs by passive diffusion into the lipoidal membrane. The various buccal formulations currently available in the market are buccal tablets, buccal patches/films, and buccal gels/ointments.

21. FACTORS CONSIDERED IN FORMULATION OF THE BUCCAL DELIVERY SYSTEMS The main factors that must be considered before formulating these buccal delivery systems are: Size of the formulation - Formulations with a size of 1 to 3 cm2 and a daily dose of 25 mg or less is preferred. The drug's molecular weight – Drugs with high molecular weight cannot readily permeate through the buccal mucosa. Hence low molecular weight drugs are often preferred. To facilitate the delivery of the former, penetration enhancers are used. Nature of the drug - Highly lipophilic drugs that can passively diffuse through the buccal mucosa is used while Formulating buccal drug delivery systems. The pH of the formulation - The pH of the carrier used in the system alters the drug's absorption. Lowering the Carrier pH increases some drugs' absorption, while the Opposite is true for other drugs. Physicochemical characteristics of the drug - The drug should be odorless and not have an unpleasant taste.

22. T HANK YOU