logging in or signing up mucoadhesive drug delivery system sachigaikwad619 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 786 Category: Science & Tech.. License: All Rights Reserved Like it (4) Dislike it (1) Added: May 23, 2011 This Presentation is Public Favorites: 1 Presentation Description No description available. Comments Posting comment... By: dkrawat86 (3 month(s) ago) Dear Sir, Please send me the ppt related to mucoadhesive drug delivery system on dkrawat86@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close By: swa77 (9 month(s) ago) sir please give me permission to download it or please you can mail me on aswethareddy666@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close By: ashwini5 (10 month(s) ago) nice presentation....can give me a permission to download it or can you mail me on ashwini.nile5@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Mucoadhesive Drug Delivery Systems : Mucoadhesive Drug Delivery Systems Prepared By – Sachin S. Gaikwad Under Guidance Of - Mrs. M.R. Narkhede M.G.V.’s Pharmacy College, Panchavati,Nashik. 23/05/2011 1 History : History Mucoadhesive drug delivery formulations were introduced in 1947 when gum tragacanth was mixed with dental adhesive powder. Examples of Orabase products are 23/05/2011 2 Traditional Routes : Traditional Routes Enteral Oral First Pass Metabolism Pre-systemic Metabolism Rectal Slow drug absorption Patient compliance issues Parenteral Intravenous Localized pain Not for sustained release Intramuscular Painful Unpredictable release rates 23/05/2011 3 Alternative Routes : Alternative Routes Transdermal (TD) Permeability issues Potent drugs Oral Transmucosal (TM) Bioadhesion issues Better permeability 23/05/2011 4 Definitions : Definitions Adhesion :Ability to stick,adhere or hold. Bioadhesion :The attachment of synthetic or biological macromolecules to a biological tissue. Mucoadhesion : The attachment of synthetic or biological macromolecules to a mucosa or mucous membrane. 23/05/2011 5 Slide 6: Mucus Mucus is a translucent and viscid which forms a thin, continuous gel blanket adherent to the epithelial surface. Thickness varies from about 50-450um It is secreted by the goblet cells lining the epithelia or by special exocrine glands with mucus cells acini. Composition: Water 95% Glycoprotein and lipids 0.5-5% Mineral salts 1% Free proteins 0.5-1% Functions: 1.Protection 2.Barrier 3.Adhesion 4.Lubrication 23/05/2011 6 Slide 7: Concept The drug can be incorporated into a cross linked polymer device that would adhere to mucosal membrane in the body .the drug can diffuse from device directly in the tissue. Decrease in frequency of administration with low dose , rate of elimination. Can bypass Firstpass metabolisum in route is other than oral 23/05/2011 7 Slide 8: Pathway to Bypass 23/05/2011 Figure 1 Different rout’s of MDDS 8 Mechanism of Mucoadhesion : Mechanism of Mucoadhesion Figure2: Mechanism of Mucoadhesion 23/05/2011 9 Slide 10: Step1 Contact Stage The first stage is characterized by the contact between the Mucoadhesive and the mucous membrane, with spreading and swelling of the formulation, initiating its deep contact with the mucus layer Step 2 Consolidation Stage In the consolidation step (Figure 2), the Mucoadhesive materials are activated by the presence of moisture. Moisture plasticizes the system, allowing the Mucoadhesive molecules to break free and to link up by weak van der Waals and hydrogen bonds . a)Diffusion Theory b) Dehydration Theory 23/05/2011 10 Slide 11: Mucoadhesion Theories There are Seven theories have been proposed till date The Theories include :- The electronic theory. The adsorption theory. Wetting theory. The diffusion theory. Dehydration Theory. Fracture theory. The mechanical theory. 23/05/2011 11 Slide 12: The electronic theory:- In this both Mucoadhesive and biological materials possess opposing electrical charges. When both materials come into contact, 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 The adsorption theory:- In this Mucoadhesive device adheres to the mucus by secondary chemical interactions, such as in van der Waals and hydrogen bonds, electrostatic attraction or hydrophobic interactions. 23/05/2011 12 Slide 13: (c) Wetting theory:- This applies to liquid systems which present affinity to the surface in order to spread over it. This affinity can be found by using measuring techniques such as the contact angle. lower the contact angle then the greater the affinity FIGURE 4 – Schematic diagram showing influence of contact angle between device and mucous membrane on bioadhesion 23/05/2011 13 Slide 14: d) The diffusion theory:- Interpenetration of both Polymer and Mucin chain Create semipermant adhesive bond Adhesion forces increases with increase in penetration It depends on diffusion coefficient 0.2-0.5 micro meter FIGURE 4 – Secondary interactions resulting from interdiffusion of polymer chains of bioadhesive device and of mucus. 23/05/2011 14 Slide 15: e) Dehydration Theory:- In dehydration theory, materials that are able to readily gelify in an aqueous environment, when placed in contact with the mucus can cause its dehydration due to the difference of osmotic pressure. The difference in concentration gradient draws the water into the formulation until the osmotic balance is reached. This process increase contact time of formulation with the mucous membrane. FIGURE 3 – Dehydration theory of mucoadhesion. 23/05/2011 15 Slide 16: (f) Fracture theory:- It analyses the force required to separate two surfaces after adhesion is established fracture theory is concerned only with the force required to separate the parts, it does not take into account the interpenetration or diffusion of polymer chains. FIGURE 5 – Regions where the Mucoadhesive bond rupture can occur. 23/05/2011 16 Slide 17: (g) The mechanical theory:- Explains the diffusion of the liquid adhesives into the micro-cracks and irregularities present on the substrate surface thereby forming an interlocked structure which gives rise to adhesion. 23/05/2011 17 Slide 18: 23/05/2011 Factors affecting mucoadhesion:- A)polymer based factors Molecular weight of the polymer Concentration of polymer used Flexibility of polymer chains Swelling factor Stereochemistry of polymer B) physical factors pH at polymer substrate interface Applied strength Contact time C) physiological factors Mucin turnover rate Diseased state 18 Slide 19: 23/05/2011 ADVANTAGES OF MUCOADHESIVE DRUG DELIVERY Prolongs the residence time of the dosage form at the site of absorption. Due to an increased residence time it enhances absorption and hence the therapeutic efficacy of the drug Rapid absorption because of enormous blood supply and good blood flow rates increase in drug bioavailability due to first pass metabolism avoidance Drug is protected from degradation in the acidic environment in the GIT Improved patient compliance- ease of drug administration faster onset of action is achieved due to mucosal surface 19 Types of Mucoadhesion Formulations : Types of Mucoadhesion Formulations 1.Solid Mucoadhesive Formulations: Tablets Inserts Lozenges 2.Semi-solid Mucoadhesive Formulations Gels Films 3.Liquid MucoadhesiveFormulations Viscous liquids Gel-forming liquids 23/05/2011 20 Targets for mucoadhesive Formulations : Targets for mucoadhesive Formulations 1) Ocular Delivery From the ocular cavity the active agent is rapidly removed by continuous formation of tears and blinking of eyelids. This result in bioavailability of active agent can be increased by ocular inserts or patches which increases residence time of drug. Pilogel® 23/05/2011 21 Slide 22: 23/05/2011 2) Nasal Cavity The nasal mucosal layer has a surface area of around 150-200cm2. Residence time 15-30 min Rhinocort® Nasacort® Beconase® 22 Slide 23: 23/05/2011 3 Buccal Cavity Delivery through buccal cavity avoids first pass metabolism and it is easy to administer. Buccal cavity delivers active agent in controlled manner where as sublingual membrane releases active agent quickly. Buccastem® treatment of nausea, vomiting. Glyceryl Trinitrate (GTN) aerosol spray 23 Slide 24: FIGURE 6: ACTION OF BUCCAL TABLET 23/05/2011 24 Slide 25: 23/05/2011 4) Vagina and rectum Figure 7 Histology of the vaginal mucosa Crinone® MDDS reduces the migration of delivery systems there by promoting therapeutic efficacy. Anacal® 25 Slide 26: 23/05/2011 5)Gastrointestinal Delivery Gastrointestinal tract is a potential site for development of Mucoadhesive based formulations. The adherent mucous gel lining the alimentary tract has thickness of 40- 50μm Mucoadhesive polymers modulate the transit time of delivery systems. The various muco adhesive polymers chitosan, poly acrylic acid, poly methacrylic acid, sodium carboxymethyl cellulose. 26 Slide 27: Drug Absorption Drug absorption is the process by which a drug leaves its site of administration and enters the general circulation Pinocytosis. Passive diffusion Facilitated passive diffusion Active transport 23/05/2011 27 Slide 28: 23/05/2011 Methods Of Evaluation No technology has still been developed specifically to analyze mucoadhesion. In vitro tests 1)Swelling Index 2)Mucoadhesive strength 3)Ex vitro residence time 4)In vitro drug release study b)In vivo methods 1. use of radioisotopes 2. use of gamma scintigraphy 3. use of pharmacoscintigraphy 4. use of electron paramagnetic resonance(EPR) oximetry 5.X ray studies 28 Slide 29: 23/05/2011 1)Swelling Index The initial weight of the tablet was determined and then tablet was placed in 6 ml phosphate buffer pH 6.8 in a petridish and then was incubated at 37 1o C. The tablet was removed at different time intervals (0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0 and 8.0 h) blotted with filter paper and reweighed (W2). The swelling index is calculated by the formula: Swelling index = 100 (W2-W1) / W1. Where, W1 = Initial weight of the tablet. W2 = Final weight of tablet. 29 Slide 30: 23/05/2011 2)Mucoadhesive strength:- The force required to break the binding between the model membrane and the Mucoadhesive is measured Figure 8: Mucoadhesion/Bioadhesion testing apparatus 30 Slide 31: 23/05/2011 3)Ex vitro residence time: The in vitro residence time for buccal tablet was determined using modified USP disintegration apparatus as reported by Nakumara et al. The medium was composed of 800 ml of phosphate buffer pH 6.8 maintained at 370. A segment of sheep buccal mucosa 3 cm length was glued to glass slab. The time necessary for complete erosion or detachment of the tablet from the mucosal surface was recorded. Figure 9: Schematic representation of ex vivo residence time. 31 Slide 32: 23/05/2011 4)In vitro drug release study: The study was carried out in USP XXIII tablet dissolution test apparatus-II (Electrolab TDT-06), employing paddle stirrer at 50 rpm and 250 ml of phosphate buffer pH 6.8 as dissolution medium maintained at 370.5 0C. The tablet was supposed to release drug from one side only hence a one side of tablet was fixed to glass disk with cyanoacrylate adhesive. The disk was placed at the bottom of the dissolution vessel. At different time interval 5 ml of sample was withdrawn and replaced with fresh medium. The samples were filtered through 0.25 μm membrane filter paper and analyzed appropriate dilution using Shimadzu-1700 UV-Visible spectrophotometer. 32 Slide 33: 23/05/2011 conclusion 33 Slide 34: 23/05/2011 REFERENCES: 1)Jain NK. Controlled and novel drug delivery. 1st ed. New Delhi: CBS Publishers & Distributors; 1997: 52-81 2)Pranshu tangari,N.V. sateesh madhav, Oral Mucoadhesive drug delivery system: a review.IJB 2011;2(1);36-46 3)Flavia Chiva carvalho,marcos Luciano Bruschi, Mucoadhesive drug delivery system, Brazilian journal of pharmaceutical sciences, vol-46, n.1- 2010 4)J Lakshmi Prasanna, N L Prasanthi, B Deepthi, S S Manikiran, N Rama Rao, Mucoadhesion: An Approach for Site – Specific Drug Delivery , Inventi Rapid: Pharm Tech Vol. 2, Issue 2 34 Slide 35: 23/05/2011 35 THANK YOU You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
mucoadhesive drug delivery system sachigaikwad619 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 786 Category: Science & Tech.. License: All Rights Reserved Like it (4) Dislike it (1) Added: May 23, 2011 This Presentation is Public Favorites: 1 Presentation Description No description available. Comments Posting comment... By: dkrawat86 (3 month(s) ago) Dear Sir, Please send me the ppt related to mucoadhesive drug delivery system on dkrawat86@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close By: swa77 (9 month(s) ago) sir please give me permission to download it or please you can mail me on aswethareddy666@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close By: ashwini5 (10 month(s) ago) nice presentation....can give me a permission to download it or can you mail me on ashwini.nile5@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Mucoadhesive Drug Delivery Systems : Mucoadhesive Drug Delivery Systems Prepared By – Sachin S. Gaikwad Under Guidance Of - Mrs. M.R. Narkhede M.G.V.’s Pharmacy College, Panchavati,Nashik. 23/05/2011 1 History : History Mucoadhesive drug delivery formulations were introduced in 1947 when gum tragacanth was mixed with dental adhesive powder. Examples of Orabase products are 23/05/2011 2 Traditional Routes : Traditional Routes Enteral Oral First Pass Metabolism Pre-systemic Metabolism Rectal Slow drug absorption Patient compliance issues Parenteral Intravenous Localized pain Not for sustained release Intramuscular Painful Unpredictable release rates 23/05/2011 3 Alternative Routes : Alternative Routes Transdermal (TD) Permeability issues Potent drugs Oral Transmucosal (TM) Bioadhesion issues Better permeability 23/05/2011 4 Definitions : Definitions Adhesion :Ability to stick,adhere or hold. Bioadhesion :The attachment of synthetic or biological macromolecules to a biological tissue. Mucoadhesion : The attachment of synthetic or biological macromolecules to a mucosa or mucous membrane. 23/05/2011 5 Slide 6: Mucus Mucus is a translucent and viscid which forms a thin, continuous gel blanket adherent to the epithelial surface. Thickness varies from about 50-450um It is secreted by the goblet cells lining the epithelia or by special exocrine glands with mucus cells acini. Composition: Water 95% Glycoprotein and lipids 0.5-5% Mineral salts 1% Free proteins 0.5-1% Functions: 1.Protection 2.Barrier 3.Adhesion 4.Lubrication 23/05/2011 6 Slide 7: Concept The drug can be incorporated into a cross linked polymer device that would adhere to mucosal membrane in the body .the drug can diffuse from device directly in the tissue. Decrease in frequency of administration with low dose , rate of elimination. Can bypass Firstpass metabolisum in route is other than oral 23/05/2011 7 Slide 8: Pathway to Bypass 23/05/2011 Figure 1 Different rout’s of MDDS 8 Mechanism of Mucoadhesion : Mechanism of Mucoadhesion Figure2: Mechanism of Mucoadhesion 23/05/2011 9 Slide 10: Step1 Contact Stage The first stage is characterized by the contact between the Mucoadhesive and the mucous membrane, with spreading and swelling of the formulation, initiating its deep contact with the mucus layer Step 2 Consolidation Stage In the consolidation step (Figure 2), the Mucoadhesive materials are activated by the presence of moisture. Moisture plasticizes the system, allowing the Mucoadhesive molecules to break free and to link up by weak van der Waals and hydrogen bonds . a)Diffusion Theory b) Dehydration Theory 23/05/2011 10 Slide 11: Mucoadhesion Theories There are Seven theories have been proposed till date The Theories include :- The electronic theory. The adsorption theory. Wetting theory. The diffusion theory. Dehydration Theory. Fracture theory. The mechanical theory. 23/05/2011 11 Slide 12: The electronic theory:- In this both Mucoadhesive and biological materials possess opposing electrical charges. When both materials come into contact, 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 The adsorption theory:- In this Mucoadhesive device adheres to the mucus by secondary chemical interactions, such as in van der Waals and hydrogen bonds, electrostatic attraction or hydrophobic interactions. 23/05/2011 12 Slide 13: (c) Wetting theory:- This applies to liquid systems which present affinity to the surface in order to spread over it. This affinity can be found by using measuring techniques such as the contact angle. lower the contact angle then the greater the affinity FIGURE 4 – Schematic diagram showing influence of contact angle between device and mucous membrane on bioadhesion 23/05/2011 13 Slide 14: d) The diffusion theory:- Interpenetration of both Polymer and Mucin chain Create semipermant adhesive bond Adhesion forces increases with increase in penetration It depends on diffusion coefficient 0.2-0.5 micro meter FIGURE 4 – Secondary interactions resulting from interdiffusion of polymer chains of bioadhesive device and of mucus. 23/05/2011 14 Slide 15: e) Dehydration Theory:- In dehydration theory, materials that are able to readily gelify in an aqueous environment, when placed in contact with the mucus can cause its dehydration due to the difference of osmotic pressure. The difference in concentration gradient draws the water into the formulation until the osmotic balance is reached. This process increase contact time of formulation with the mucous membrane. FIGURE 3 – Dehydration theory of mucoadhesion. 23/05/2011 15 Slide 16: (f) Fracture theory:- It analyses the force required to separate two surfaces after adhesion is established fracture theory is concerned only with the force required to separate the parts, it does not take into account the interpenetration or diffusion of polymer chains. FIGURE 5 – Regions where the Mucoadhesive bond rupture can occur. 23/05/2011 16 Slide 17: (g) The mechanical theory:- Explains the diffusion of the liquid adhesives into the micro-cracks and irregularities present on the substrate surface thereby forming an interlocked structure which gives rise to adhesion. 23/05/2011 17 Slide 18: 23/05/2011 Factors affecting mucoadhesion:- A)polymer based factors Molecular weight of the polymer Concentration of polymer used Flexibility of polymer chains Swelling factor Stereochemistry of polymer B) physical factors pH at polymer substrate interface Applied strength Contact time C) physiological factors Mucin turnover rate Diseased state 18 Slide 19: 23/05/2011 ADVANTAGES OF MUCOADHESIVE DRUG DELIVERY Prolongs the residence time of the dosage form at the site of absorption. Due to an increased residence time it enhances absorption and hence the therapeutic efficacy of the drug Rapid absorption because of enormous blood supply and good blood flow rates increase in drug bioavailability due to first pass metabolism avoidance Drug is protected from degradation in the acidic environment in the GIT Improved patient compliance- ease of drug administration faster onset of action is achieved due to mucosal surface 19 Types of Mucoadhesion Formulations : Types of Mucoadhesion Formulations 1.Solid Mucoadhesive Formulations: Tablets Inserts Lozenges 2.Semi-solid Mucoadhesive Formulations Gels Films 3.Liquid MucoadhesiveFormulations Viscous liquids Gel-forming liquids 23/05/2011 20 Targets for mucoadhesive Formulations : Targets for mucoadhesive Formulations 1) Ocular Delivery From the ocular cavity the active agent is rapidly removed by continuous formation of tears and blinking of eyelids. This result in bioavailability of active agent can be increased by ocular inserts or patches which increases residence time of drug. Pilogel® 23/05/2011 21 Slide 22: 23/05/2011 2) Nasal Cavity The nasal mucosal layer has a surface area of around 150-200cm2. Residence time 15-30 min Rhinocort® Nasacort® Beconase® 22 Slide 23: 23/05/2011 3 Buccal Cavity Delivery through buccal cavity avoids first pass metabolism and it is easy to administer. Buccal cavity delivers active agent in controlled manner where as sublingual membrane releases active agent quickly. Buccastem® treatment of nausea, vomiting. Glyceryl Trinitrate (GTN) aerosol spray 23 Slide 24: FIGURE 6: ACTION OF BUCCAL TABLET 23/05/2011 24 Slide 25: 23/05/2011 4) Vagina and rectum Figure 7 Histology of the vaginal mucosa Crinone® MDDS reduces the migration of delivery systems there by promoting therapeutic efficacy. Anacal® 25 Slide 26: 23/05/2011 5)Gastrointestinal Delivery Gastrointestinal tract is a potential site for development of Mucoadhesive based formulations. The adherent mucous gel lining the alimentary tract has thickness of 40- 50μm Mucoadhesive polymers modulate the transit time of delivery systems. The various muco adhesive polymers chitosan, poly acrylic acid, poly methacrylic acid, sodium carboxymethyl cellulose. 26 Slide 27: Drug Absorption Drug absorption is the process by which a drug leaves its site of administration and enters the general circulation Pinocytosis. Passive diffusion Facilitated passive diffusion Active transport 23/05/2011 27 Slide 28: 23/05/2011 Methods Of Evaluation No technology has still been developed specifically to analyze mucoadhesion. In vitro tests 1)Swelling Index 2)Mucoadhesive strength 3)Ex vitro residence time 4)In vitro drug release study b)In vivo methods 1. use of radioisotopes 2. use of gamma scintigraphy 3. use of pharmacoscintigraphy 4. use of electron paramagnetic resonance(EPR) oximetry 5.X ray studies 28 Slide 29: 23/05/2011 1)Swelling Index The initial weight of the tablet was determined and then tablet was placed in 6 ml phosphate buffer pH 6.8 in a petridish and then was incubated at 37 1o C. The tablet was removed at different time intervals (0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0 and 8.0 h) blotted with filter paper and reweighed (W2). The swelling index is calculated by the formula: Swelling index = 100 (W2-W1) / W1. Where, W1 = Initial weight of the tablet. W2 = Final weight of tablet. 29 Slide 30: 23/05/2011 2)Mucoadhesive strength:- The force required to break the binding between the model membrane and the Mucoadhesive is measured Figure 8: Mucoadhesion/Bioadhesion testing apparatus 30 Slide 31: 23/05/2011 3)Ex vitro residence time: The in vitro residence time for buccal tablet was determined using modified USP disintegration apparatus as reported by Nakumara et al. The medium was composed of 800 ml of phosphate buffer pH 6.8 maintained at 370. A segment of sheep buccal mucosa 3 cm length was glued to glass slab. The time necessary for complete erosion or detachment of the tablet from the mucosal surface was recorded. Figure 9: Schematic representation of ex vivo residence time. 31 Slide 32: 23/05/2011 4)In vitro drug release study: The study was carried out in USP XXIII tablet dissolution test apparatus-II (Electrolab TDT-06), employing paddle stirrer at 50 rpm and 250 ml of phosphate buffer pH 6.8 as dissolution medium maintained at 370.5 0C. The tablet was supposed to release drug from one side only hence a one side of tablet was fixed to glass disk with cyanoacrylate adhesive. The disk was placed at the bottom of the dissolution vessel. At different time interval 5 ml of sample was withdrawn and replaced with fresh medium. The samples were filtered through 0.25 μm membrane filter paper and analyzed appropriate dilution using Shimadzu-1700 UV-Visible spectrophotometer. 32 Slide 33: 23/05/2011 conclusion 33 Slide 34: 23/05/2011 REFERENCES: 1)Jain NK. Controlled and novel drug delivery. 1st ed. New Delhi: CBS Publishers & Distributors; 1997: 52-81 2)Pranshu tangari,N.V. sateesh madhav, Oral Mucoadhesive drug delivery system: a review.IJB 2011;2(1);36-46 3)Flavia Chiva carvalho,marcos Luciano Bruschi, Mucoadhesive drug delivery system, Brazilian journal of pharmaceutical sciences, vol-46, n.1- 2010 4)J Lakshmi Prasanna, N L Prasanthi, B Deepthi, S S Manikiran, N Rama Rao, Mucoadhesion: An Approach for Site – Specific Drug Delivery , Inventi Rapid: Pharm Tech Vol. 2, Issue 2 34 Slide 35: 23/05/2011 35 THANK YOU