MECHANISM OF PERMEATION OF DRUG IN BUCCAL DRUG DELIVERY SYSTEM.pptx

PREPARED BY : SUPRITH D.
M.PHARMACY , 1ST SEM.
RR COLLEGE OF PHARMACY , BANGALORE.
SPECIAL THANKS TO PAWAN DHAMALA.

1. 27-04-2022 © R R INSTITUTIONS , BANGALORE 1 MODIFIED DRUG DELIVERY SYSTEM MECHANISM OF PERMEATION OF DRUG IN BUCCAL DRUG DELIVERY SYSTEM RR COLLAGE OF PHARMACY Submitted by ; SUPRITH D 1 ST SEM M pharm Dept. of Pharmaceutics Submitted to; Dr. A Geetha Lakshmi HOD Dept. of Pharmaceutics

2. CONTENTS Introduction to bioadhesion Mechanism of bioadhesion Factors affecting bioadhesion Theories of bioadhesion Types of pathway for permeation 27-04-2022 © R R INSTITUTIONS , BANGALORE 2

3. BIOADHESION/MUCOADHESION Bioadhesion may be defined as the state in which two materials, at least one of which is biological in nature, are held together for longer periods of time by interfacial forces. When the adhesive attachment is to mucus or a mucous membrane, the phenomenon is referred to as mucoadhesion . Mechanism of bioadhesion : For bioadhesion to occur , three stages are involved 1. An intimate contact between a bioadhesive and a membrane either from a good wetting of the bioadhesive and a membrane or from the swelling of bioadhesive . 2. Penetration of the bioadhesive into the tissue takes place. 3. Inter penetration of the chains of the bioadhesive with mucous takes place low chemical bonds can then settle 27-04-2022 © R R INSTITUTIONS , BANGALORE 3

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7. POLYMER RELATED FACTOR Molecular weight of polymer; T he interpenetration of polymer molecules is favored by low molecular weight polymers, whereas entanglements are favored at higher molecular weights. The optimum molecular weight for maximum mucoadhesive depend on type of polymer. Crosslinking and swelling of polymer: •Cross-link density is inversely proportional to the degree of swelling. •The lower the cross-link density ,the higher the flexibility and hydration rate; the larger the surface area of the polymer, better the mucoadhesion •High moisture and swelling results in a slippy mucilage leads to easy removal from substrate. 27-04-2022 © R R INSTITUTIONS , BANGALORE 7

8. Concentration of mucoadhesive polymer : • Optimum concentration of polymer is required to get best mucoadhesion. •In highly concentration coiled molecules of polymer become solvent poor and chains available for bioadhesion are less. •In low concentration bioadhesion of polymer also decrease Spatial conformation : spatial configuration of a molecule is also an important factor for bioadhesion . Despite their high molecular weight ,dextran(195000 Dalton) have similar bioadhesive strength to that of PEG , with molecular weight of 200000 Dalton .this is because helical structure of dextrans may shield many adhesively active groups, responsible for adhesion ,unlike PEG molecules which have a linear configuration. 27-04-2022 © R R INSTITUTIONS , BANGALORE 8

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10. ENVIRONMENTAL FACTORS PH: Adhesion of bioadhesives possessing ionizable groups affected by pH at interface. •If the local PH is above the pk of the polymer , it will be largely ionized. •If the ph is below the pk of the polymer , it will largely unionized. ex : The maximum adhesive strength of the poly acrylic acid is found at Ph 4-5 and decreases above Ph 6 Initial contact time : Greater the initial contact time between bioadhesive and substrate ,the greater the swelling and interpenetration of polymer chains . 27-04-2022 © R R INSTITUTIONS , BANGALORE 10

11. PHYSIOLOGICAL VARIABLES Mucin turnover : The natural turnover of mucin molecules is important for two reason • It is expected to limit the residence time of mucoadhesive on the mucus layer. No matter how high the mucoadhesive strength, mucoadhesive are detached from the surface due to mucin turnover. • Secondly, mucin turnover results in substantial amounts of soluble mucin molecules. The molecules interact with mucoadhesive before they have a chance to interact with mucus layer. Surface fouling is unfavorable for mucoadhesion to the tissue surface . 27-04-2022 © R R INSTITUTIONS , BANGALORE 11

12. Disease state : Physiochemical properties of the mucus are known to change during disease conditions such as common cold, bacterial and fungal infection etc. the exact structural changes taking place in mucus under these condition is poorly understood 27-04-2022 © R R INSTITUTIONS , BANGALORE 12

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14. Theories of bioadhesion 27-04-2022 © R R INSTITUTIONS , BANGALORE 14

15. Wetting Theory The wetting theory applies to liquid or low viscosity bio adhesives. Adhesive agents penetrate into the surface irregularity of substrate and ultimately harden and producing many adhesive anchors. • This affinity can be found by using measuring techniques such as the contact angle . • Lower the contact angle then the greater the affinity. • The contact angle should be equal or close to zero to provides adequate spreadability. 27-04-2022 © R R INSTITUTIONS , BANGALORE 15

16. The spreading coefficient (S AB ) can be calculated from the surface energies of the solid and liquids using the equation: S AB = γ B – γ A – γ AB Where γ A is the surface tension (energy) of the liquid A γ b is the surface energy of the solid Band γ AB is the interfacial energy between the solid and liquid. The greater the individual surface energy of mucus and device concerning the interfacial energy, the greater the adhesion work, i.e., the greater the energy needed to separate the two phases 27-04-2022 © R R INSTITUTIONS , BANGALORE 16

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18. Diffusion Theory: According to this theory, the polymer chains and the mucus mix to a sufficient depth to create a semi-permanent adhesive bond. Mucus chain present on the mucus membrane Ex: Glycoprotein Polymeric chains having ability to build bonds with mucus chain Ex: hydrogen bonding group (-OH) ,(-COOH) The exact depth to which the polymer chains penetrate the mucus depends on the diffusion coefficient and the time of contact. This diffusion coefficient, in turn, depends on the value of molecular weight between cross links and decreases significantly as the cross linking density decreases 27-04-2022 © R R INSTITUTIONS , BANGALORE 18

19. Below equation helps to evaluate the interpenetration depth of polymer and mucin chains L = (tDb)½ Where t is the contact time and Db is the diffusion coefficient of the mucoadhesive material in the mucus. 27-04-2022 © R R INSTITUTIONS , BANGALORE 19

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21. Electronic Theory It is based on the premise that both mucoadhesive and biological material poses opposing g electrical charges. Mucus membrane have negative charge because of presence of sialic acid and sulphate residue Thus, when both the materials come in contact with each other transfer of electron takes place leading to the building of double electronic layer at the interface , where the attractive forces with in the double layer determines the mucoadhesive strength . 27-04-2022 © R R INSTITUTIONS , BANGALORE 21

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23. Fracture Theory Most used theory in studies on the mechanical measurement of mucoadhesion It analyses the force required to separate two surfaces after adhesion is established It is concerned only with the force required to separate parts It does not take in to the account of inter-penetration or diffusion of polymeric chains 27-04-2022 © R R INSTITUTIONS , BANGALORE 23

24. The fracture strength is equivalent to adhesive strength as given by G = (E ε. / L) ½ Where: E- Young’s modules of elasticity ε- Fracture energy L- Critical crack length when two surfaces are separated 27-04-2022 © R R INSTITUTIONS , BANGALORE 24

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26. Adsorption Theory According to this theory, after an initial contact between two surfaces, the materials adhere because of surface forces acting between the atoms in the two surfaces. Two types of chemical bonds such as primary covalent (permanent) and secondary chemical bonds (including electrostatic forces, vander-waals forces and hydrogen and hydrophobic bonds) are involved in the adsorption process 27-04-2022 © R R INSTITUTIONS , BANGALORE 26

27. 27-04-2022 © R R INSTITUTIONS , BANGALORE 27 MECHANISM OF DRUG ABSORPTION There are two permeation pathways for passive drug transport across the oral mucosa: Paracellular Transcellular 1) Paracellular permeation ; Drug permeation is in between epithelial cells. Aqueous filled pores are present Primary root for hydrophilic drug The paracellular transport is not suitable for the transport of large macromolecules and is generally restricted to the compounds of molecular radii less than 11Å Several peptide drugs, such as octreotide, vasopressin analog desmopressin, and thyrotropin-releasing hormone are believed to absorb by this route

28. 2) Transcellular permeation; Drug permeation through the epithelial cells involves transport across the apical cell membrane to the intracellular space and the basolateral membrane Lip id rich plasma membrane is present Primary root for lipophilic drugs The drug molecules have to partition into the cell membranes at the apical side (the mucosa layer) followed by entering the intracellular space after escaping from the membranes due to the concentration gradient. While residing in the intracellular space, the molecule partitions into cell membranes at the basolateral side (blood side) followed by entrance into the blood in the systemic circulation. . 27-04-2022 © R R INSTITUTIONS , BANGALORE 28

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31. REFRENCES N.K Jain Controlled and Novel Drug Delivery System S.P.Vyas and R.K.Khar , Controlled Drug Delivery System Encyclopaedia of Controlled Drug Delivery System 27-04-2022 © R R INSTITUTIONS , BANGALORE 31

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