Mucoadhesive Drug Delivery system

1. MUCOADHESIVE DRUG DELIVERY-
FORMULATION & EVALUATION
PRESENTED BY: Alexa Jacob
1st yr M.Pharm, Pharmaceutics
St.Joseph’s college of pharmacy, cherthala
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2. CONTENTS
 MECHANISM OF DRUG PERMEATION
 FORMULATION OF BUCCAL MUCOADHESIVE DRUG DELIVERY
 EVALUATION OF BUCCAL MUCOADHESIVE DRUG DELIVERY
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3. MECHANISM OF DRUG PERMEATION
(a) Electronic theory:
 According to this theory, electron transfer occurs upon contact of an adhesive polymer with a
mucus glycoprotein network because of differences in their electronic structure.
 This results in the formation of an electrical double layer at the interface.
 Adhesion occurs due to attractive forces across the double layer.
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4. (b) Absorption theory:
 According to this theory,after an initial contact between two surfaces, the material adheres
of surface forces acting between the atoms in two surfaces.
 Two types of chemical bonds resulting from these forces can be distinguished:-
• Primary chemical bonds
• Secondary chemical bonds
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5. (c) Wetting theory:
 Wetting theory is predominantly applicable to liquid bioadhesive systems and analyses adhesive and
contact behaviour in terms of the ability of a liquid or a paste to spread over a biological system.
 The work of adhesion(expressed in terms of surface & interfacial tension, Y being defined as the
energy per cm² released when an interface is formed) is given by:
Wa = YA + YB - YAB
Where ‘A’ & ‘B’ refer to biological membrane and the bioadhesive formulation respectively.
 The work of cohesion is given by:
Wc = 2YA or YB
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6.  For a bioadhesive material B spreading on a biological substrate A, the spreading
coefficient is given by:
SB/A = YA – ( YB + YAB )
SB/A should be positive for a bioadhesive material to adhere to a biological membrane.
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7. (d) Diffusion theory:
 According to this theory, the polymer chains and the mucus mix to a sufficient depth to create a
semi-permanent adhesive bond.
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8. (e) Fracture theory:
 This theory attempts to relate the difficulty of separation of two surfaces after adhesion.
 Fracture theory equivalent to adhesive strength is given by:
G = ( E ε/L)½
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9. FORMULATIONS FOR BUCCAL MUCOADHESIVE DRUG
DELIVERY
1) BUCCAL MUCOADHESIVE TABLETS:
 Buccal mucoadhesive tablets are dry dosage forms that are to be moistened after placing in
contact with buccal mucosa.
 They can be formulated into monolithic,partially coated or multi-layered matrices.
 These tablets are solid dosage forms that are prepared by the direct compression of powder and
can be placed into contact with the oral mucosa and allowed to dissolve or adhere depending on
the type of excipients incorporated into the dosage form.
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10. LIMITATIONS:
 The small surface of contact with the mucosa
 Their lack of physical flexibility
 It is difficult to obtain high release rates, which is required for some drugs
 The extent & frequency of contact may cause irritation following chronic application on the buccal &
sublingual mucosa
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11. 2) MUCOADHESIVE HYDROGELS:
 These are hydrophilic matrices that are capable of swelling when placed in aqueous media.
 Hydrogels, which release the drug by swelling and thereby allowing drug transport through the
spaces in the polymer network, are being widely studied for their use in bioadhesive gels.
 Polyacrylic-based hydrogels have also been extensively studied.
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12.  Various polymers are used to prepare mucoadhesive hydrogel such as cellulose derivatives ,natural
gums ,poly acrylates.
 To obtain mucoadhesive hydrogel , two properties have to be optimised.
(1)polarity of polymer surface.
(2)molecular mobility of polymer.
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13. 3) BUCCAL PATCHES :
 Buccal adhesive patches are modified release dosage form that have potential to provide controlled
drug delivery from 1 to 24 hrs .
 They adhere to buccal mucosa for extended period of time.
 Adhesive polymer itself act as drug carrier or adhesive layer link between drug loaded layer and
mucosa.
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14.  The use of an impermeable backing layer will maximize the drug concentration gradient and prolongs
adhesion
 Size-generally 1-16 cm²
 Two methods used to prepare adhesive patches include solvent casting and direct milling .
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15. 4) CHEWING GUMS :
 The main target mucosa for drug absorption is sublingual mucosa.
 Chewing gums formulations consist generally of a gum base of cellulosic or acrylic polymer.
 Drug release from chewing gum formulations is generally not as immediate as in the case for the
dissolving tablets.
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16. LIMITATIONS :
 The drug released into the saliva disappears rapidly from the oral cavity because of involuntary
swallowing.
 The concentration of drug in the oral cavity is always decreasing as a result of salivary dilution.
 The drug is not protected from the environment found in the oral cavity.
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17. 5) HOLLOW FIBERS :
 It is an alternative approach for the chewing gum formulations.
 Eg: The design of a microporous hollow fiber of polysulfone intended for the delivery of histrelin
(LHRH agonist ).
 This fiber is intended to be placed in the buccal cavity for oral mucosal drug delivery.
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18. EVALUATIONS OF BUCCAL MUCOADHESIVE DRUG
DELIVERY
IN-VITRO METHODS
1) TENSILE STRESS MEASUREMENT:
(Wilhelmy plate technique) :
 This method is used to measure the mucoadhesive strength.
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19. 2) SHEAR STRESS MEASUREMENT:
 This method measure the force that cause a mucoadhesive to slide over the mucus layer in
parallel to their place of contact of adhesion.
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20. 3) ADHESION WEIGHT METHOD:
 In this method the weight of adherent particle was determined by flowing a suspension of an ion
exchange resin particles over the inner mucosal surface of a section of animal intestine (guinea pig).
 This method has limited value due to poor data bioavailability.
 But it was possible to determine the effect of particle size and charge on the adhesion with everted
intestine after 5 minutes contact.
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21. 4) FLUORESCENT PROBE METHOD :
 For the determination of the bioadhesive potential of large number of polymer, the Fluorescent
method is used.
 In the technique labelling the lipid bilayer and memberane protein with the fluorescent probes
(pyrene and fluorescein isothiocynate).
 Addition of polymers to this substrate surface compressed the lipid bilayer or protein causing a
change in fluorescence, as compared to control cells.
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22. 5) FLOW CHANNEL METHOD :
 This method was developed by Mikos and Peppas.
 A 2% w/w aqueous solution of bovine submaxillary mucin, thermostatic at 37ºC is filled in a glass
made up of thin channel.
 Humid air at 37ºC was passed through glass channel.
 The adhesion property is calculated by placing a particle of bioadhesive polymer on the mucin gel
and its static and dynamic behaviour is monitored at frequent intervals using a camera.
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23. 6) FALLING SPHERE METHOD :
 The falling sphere method was used for characterize the mucoadhesive strength.
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1. Glass burette (50 ml), 2. Mustard grains of uniform size, 3.
Homogenized mixture of 10% mucus solution, 4. Burette stand.
FALLING SPHERE METHOD

24. 7) COLLOIDAL GOLD STAINING METHOD :
 The technique employed red colloidal gold particles which were stabilized by adsorbed mucin
molecules ( mucin-gold conjugates).
 Upon interaction with the mucin-gold conjugates , bioadhesive hydrogels developed a red colour
the surface.
 Thus the interaction between them could easily be quantified either by the measurement of the
intensity of red colour on the hydrogel surface or by the measurement of the decrease in
concentration of the conjugates from the absorbance changes at 525 nm.
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25. 8) VISCOMETRIC METHOD :
 Hassan and Gallo used simple viscometer to quantify the mucin-polymer bioadhesion bond
 Viscosities of 15% w/v percin gastric mucin dispersions in 0.1 N Hcl or 0.1 N acetate buffer were
measured with Brookefield viscometer.
 The Brookefield visometer measure the bioadhesion bond strength in the presence or absence of
neutral, anionic and cationic polymers.
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26. 9) ADHESION NUMBER :
 With a mucoadhesive in the form of small particles , the adhesion number can be used as a
for mucoadhesion.
 The adhesion number is typically represented by the following equation:
Na = (N/N0) X 100
Where Na is the adhesion number
N0 is the total number of applied particles
N is the number of particles attached to the substrate
As the adhesion strength increases, the adhesion number also increases.
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27. 10) ELECTRICAL CONDUCTANCE:
 The semisolid mucoadhesive ointments are tested by electrical conductance method.
 For measuring the electrical conductance we use a modified rotational viscometer.
 In this method the artificial membrane in the artificial saliva is used, the adhesion of orabase,
carbopol, cudispert, guar gum and methylcellulose is calculated.
 In the presence of adhesive the conductance is comparatively low, as the adhesive was removed,
value increased to final value, which corresponds to the conductance of saliva, which indicates the
absence of adhesion.
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28. REFERENCE
 Controlled drug delivery, concepts & advances;Suresh.P.Vyas ,Roop.K.Khar, Pg no: 257-300
 Controlled & novel drug delivery, by N.K Jain , Pg no: 353-380
 Singh.J, Deep.P;A review article on mucoadhesive buccal drug delivery system,International journal
of pharmaceutical sciences & research,2013, vol 4(3),916-927
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29. THANKYOU…
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