FORMULATION AND EVALUATION OF MUCOADHESIVE BI-LAYER TABLETS OF SIMVASTATIN USING NTURAL POLYMER

1. Dept .OF Quality Assurance Techniques
MGV’s College of Pharmacy, Nashik-03.
1
Seminar
On
Project Work
By
Mr.Kanwale Nitin P.

2. CONTENT
• Introduction
• Drug Profile
• Excipients Profile
• Objectives
• Plan of Work
• Experimental
• Result and Discussion
• References
2

3. Introduction
3

4. Basis of mucoadhesion:
‘Bioadhesion' as the state wherein two materials out of which at least one of
biological origin, are held together for an extended period of time by interfacial
forces. Scientist Peppas and Buri in 1985 defined Bioadhesion as “the
attachment of synthetic or biological macromolecules to a biological tissue”.
Bioadhesive is defined as a substance that is capable of interacting with
biological material and being retained on them or folding together for extended
period of time.
4

5. Different approaches of mucoadhesive drug delivery:
1.Buccal drug delivery system
2.Sublingual drug delivery system
3.Rectal drug delivery system
4.Nasal drug delivery system
5.Vaginal drug delivery system
6.Occular drug delivery system
7.Gastrointestinal drug delivery system
The present work was devoted to develop buccoadhesive drug delivery system.
5

6. Buccal Adhesive Drug Delivery System:
Drug delivery via the membranes of the oral cavity can be subdivided
as follows.
• Sublingual delivery, in which the administration of drug via the sublingual
mucosa to the systemic circulation.
• Buccal delivery, in which the administration of drug via the buccal mucosa
(the lining of cheek) to the systemic circulation via internal jugular vein.
• Local delivery, for the treatment of conditions of the oral cavity, principally
aphthous ulcers, fungal conditions and periodontal diseases by applications
of the bioadhesive system either to the palate, the gingiva, or the cheek.
6

7. Overview of the Oral Cavity
The various target sites for drug delivery and absorption may include the
upper and lower lips, gums (gingiva), hard palate, soft palate, floor of the mouth
(sublingual), tongue, and buccal mucosal tissue (cheek).
A) Anatomy of the Oral Cavity
It can be divided into three functional zones;
1. The mucus
7

8. 2. The hard palate and gingiva
3. Specialized zones consisting of the borders of the lips
B) The Mucus Layer
C) Environment of Oral Cavity
D) Permeability Through Oral Mucosa
E) Salivary Flow
8

9. Mucoadhesion:
For drug delivery purpose, the term bioadhesion implies attachment of a drug
carrier system to a specific biological location.
Mechanism of Mucoadhesions:
9
Theory of Adhesion Mechanism of Adhesion
Adsorption Secondary chemical bonds such as van der Waals forces, hydrophobic interactions,
electrostatic attractions, and hydrogen bonds between mucus and polymer.
Diffusion Entanglements of the polymer chains into mucus network.
Electronic Attractive forces across electrical double layer formed due to electron transfer
across polymer and mucus.
Wetting Analyzes the ability of a paste to spread over a biological surface and calculates the
interfacial tension between the two [110]. The tension is considered proportional to
X1=2, where X is the Flory polymer–polymer interaction parameter. Low values of
this parameter correspond to structural similarities between polymers and an
increased miscibility.
Fracture Relates the force necessary to separate two surfaces to the adhesive bond strength

10. Factors Affecting Mucoadhesion:
Polymer Related Factors-
• Molecular Weight
• Concentration of Active Polymer
• pH
• Applied Strength
• Initial Contact Time
• Swelling
Physiological Variables-
• Mucin Turnover
• Disease State
10

11. Drug Profile
11

12. Simvastatin:
Molecular Structure:
.
Category: Lipid lowering agent.
Dose: 10 mg,20 mg,40 mg,80 mg.
Description: A white to off white, non hygroscopic , crystalline
powder
Melting Point: 135°C to 138°C. 12

13. Solubility: It is practically insoluble in water,and freely soluble in chloroform, methanol
and ethanol.
Storage: Store in well close container.
Bioavailability: < 5% oral
Half life: 2 to 3 hrs.
Dose: 10 mg,20 mg, 40mg ,80 mg.
13

14. Polymer Profile
14

15. Polymer profile
15
• SODIUM ALGINATE:
 Chemical name: sodium alginate.
 Description: Sodium alginate occurs as an odorless and tasteless, white to pale
yellowish-brown colored powder.
 Functional Category: used in mucoadhesive drug delivery ; rate-controlling
polymer for sustained release, stabilizing agent, diluent in capsule formulation,
Tablet binder, disintegreting agent.
 Melting point: >300 c
 Solubility:Practically insoluble in ethanol (95%),ether,chloroform and ethanol/water
mixer in which ethanol content is 30%.also practically insoluble in other organic
solvent and aq. Acidic solution in which ph <3.slowly soluble in water, forming
viscous colloidal solution.

16. • GUAR GUM:
 Synonyms: Gum cyamopsis, Guar flour
 Melting point: decomposition occurs within 30 minutes at 260°C.
 Functional Category: Thickener, stabilizer , emulsifire
 Description: white to yellowish white, nearlly oduorless free flowing
powder
 .Solubility:Insoluble in ethanol
16

17. Objective
17

18. Objective of study:
simvastatin is a HMG –COA reductes inhibitor, used in treatment of
hyperlipidemia. Usual dosage regimen is 5mg, 2 times a day or 10mg once daily
having t1/2 2-3 hrs,undergoes hepatic first pass metabolism and low oral
bioavailability,higher acid hydrolysis in stomach. Therefore in present study
attempt has been done to formulate and evaluate the buccal mucoadhesive of
simvastatin. Buccal delivery has been choose because of the reach blood supply,
bypasses hepatic first pass metabolism and direct access to systemic circulation,
the oral mucosal route is suitable for drugs.
18

19. Plan of Work
19

20. Plan of work :
1.Literature review
2. Selection and procurement of drug
3. Selection and procurement of the polymers
4. Preformulation study of the drug:
• Organoleptic properties
• Solubility
• FTIR- spectroscopy
5 Characterization of polymers:
• Organoleptic Properties
• FTIR- spectroscopy 20

21. 6 .Formulation of buccoadhesive tablet of simvastatin by direct
compression method
8 Evaluation of buccoadhesive tablets
- Hardness
- Average Weight
- Swelling Index
- Surface pH determination
- Ex-vivo Bioadhesion study
21

22. Experimental
22

23. Preformulation studies :
1) Organoleptic properties
2) FTIR Spectroscopy
3) Characterization of polymers:
1.organoleptic properties
2. FTIR spectroscopy
6) Drug-Excipient compatibility
23

24. 24
Sr. No Range cm-1 Fun Gr.
1 3551.07 O-H streching
2 3011,2968.55,2872 C-H streching
3 1697.41 C=O ester
4 1456.30

25. 25
Sr. No Range cm-1 Fun Gr.
1 3558.78 O-H Stretching
2 2958.90 C-H Streching
3 3010.11 C-H Streching
4 1697.41 C=O ester

26. Formula for mucoadhesive tablet:
26
Ingradient
(mg)
Formulation
F1(1:3) F2(1:4) F3(1:5)
Simvastatin 50 50 50
Sodium alginate 22.5 30 37.5
Guar gum 7.5 7.5 7.5
PEG 6000 2.25 2.25 2.25
Mannitol 61.75 54.25 46.75
aerosil 4.5 4.5 4.5
Mg.stearate 1.5 1.5 1.5
Ethyl-cellulose 50 50 50
Total 200 200 200

27. Evaluation of buccal mucoadhesive tablet
• Hardness
• Weight variation:
• Surface pH study
• Swelling study
• Ex-vivo Bioadhesion study
27

28. Result and Discussion
28

29. EVAIUATIONOFPREPAREDBUCCALTABLET
PARAMETER F1 (1:3) F2 9 (1:4) F3 (1:5)
HARDNESS(Kg/cm
square)
3.5 4 4
WEIGHT
VARIATION
196.28 197.78 197.8
SURFACE pH 6.89 6.92 6.88
SWELLING
INDEX(%)
34.3 35.1 53.4
EX-VIVO
BIOADHESION
STUDY(N)
0.39 0.39 0.49
29

30. Conclusion
30

31. Conclusion:
FT-IR study reports shows that there is drug-polymer compatibility.
Sodium alginate gives significant drug retarding ability as well as prevent
burst release of drug.
Guar gum shows good bioadhesion property & this may be aided by sodium
alginate
Being a high viscous polymer (sodium alginate) gives significant % swelling
for 4h, which is essential for retarding drug release.
31

32. Future Scope
32

33. Future Scope:
1. In vivo pharmacokinetic study of buccoadhesive tablets of simvastatin in
both the animals and humans.
2. In vitro-in vivo correlation.
3. Development of buccoadhesive tablets of simvastatin using different
combinations of various mucoadhesive polymers.
4. Development of multi-layered buccoadhesive tablets of simvastatin using
different polymers.
5. Development of buccoadhesive patches of simvastatin using different
combinations of various mucoadhesive polymers.
6. Development of buccoadhesive tablets of such other drugs which undergoes
extensive first pass metabolism in the liver or extensive acid hydrolysis in the
stomach.
33

34. References
34

35. References:
1) Ahuja A, Khar RK, Ali J. Mucoadhesive drug delivery system. Drug Dev Ind
Pharm 1997;23(5):489-519..
2) Vyas SP, Khar RK. Controlled Drug Concepts and Advances. 1st ed. Vallabh
Prakashan: Delhi; 2002. p. 292-94.
3) Salamat-Millar N, Chittchang M, Johnston TP. The use of mucoadhesive
polymers in buccal drug delivery. Adv Drug Deliev Rev 2005;57:1666-1691.
4) K.Aiswarya et al.,Formulation and Evaluation of Mucoadhesive Bi-layer buccal
Tablets of Labetalol Hydrochloride Using Natural Polymers; research article,
published in IJAPBC-VOL-1(3),jul-sep,2012.
5) Rathbone, M.J. and Hadgraft, J., Absorption of drugs from the human oral cavity.
Int. J. Pharm. 1991; 74: 9-24.
6) Lewis S, Subranian G, Pandey S, Udupa N. Design And Evaluation
Pharmacokinetic Study of MucoadhesiveBuccal Tablets of Nicotine for Smoking
Cessation. Ind J Pharm Sci 2006; 68:829-31.
35

36. THANK YOU
36