Dept .OF Quality Assurance Techniques

MGV’s College of Pharmacy, Nashik-03.1

Seminar On

Project Work

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

By

Mr.Kanwale Nitin P.

CONTENT

•Introduction

•Drug Profile

•Excipients Profile

•Objectives

•Plan of Work

•Experimental

•Result and Discussion

•References

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Introduction

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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.

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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

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.

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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

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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

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Mucoadhesion:For drug delivery purpose, the term bioadhesion implies attachment of a drug

carrier system to a specific biological location.

Mechanism of Mucoadhesions:

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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

and is often used to calculate fracture strength of adhesive bonds.

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

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Drug Profile

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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 powderMelting Point: 135°C to 138°C. 12

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

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Polymer Profile

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Polymer profile

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• 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.

• 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

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Objective

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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.

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Plan of Work

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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

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

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Experimental

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Preformulation studies :

1) Organoleptic properties

2) FTIR Spectroscopy

3) Characterization of polymers:

1.organoleptic properties

2. FTIR spectroscopy

6) Drug-Excipient compatibility

23

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

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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

Formula for mucoadhesive tablet:

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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

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

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Result and Discussion

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EVAIUATION OF PREPARED BUCCAL TABLET

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

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Conclusion

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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.

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Future Scope

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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.

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References

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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.

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THANK YOU

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