PREPARATION AND CHARACTERIZATION OF MICROCAPSULES OF VENLAFAXINE

Presented by

M.Sahadev

B.PharmUnder the Guidance ofV.Sampath Reddy

INTRODUCTION

LITERATURE SURVEY

AIM AND OBJECTIVE

DRUG AND POLYMER PROFILE

MATERIALS AND METHODS

RESULTS AND DISCUSSION

SUMMARY AND CONCLUSION

REFERENCES

contents

INTRODUCTION

Literature survey

Georgarakis et al., Microcapsules of salbutamol sulphate with ethylcellulose were prepared

using an emulsion-solvent evaporation technique and by the use of two different stirrer types,

propeller and magnet. Different amounts of drug were added in order to obtain various drug to

polymer ratios. The physical properties, loading efficiency and dissolution rate depended on

the emulsion-solvent evaporation technique and on the drug to polymer ratio. Tween 80 was

used as a dispersing agent. For a given drug to polymer ratio the percentage amount of Tween

80 affected the release of salbutamol sulphate and the size distribution of microcapsules.

Tarun K. Mandal et al.,23 Preparation of biodegradable microcapsules of zidovudine using

solvent evaporation: Effect of the modification of aqueous phase. The objective of the present

investigation was to improve the efficiency of encapsulation of zidovudine (AZT) in poly

(lactide/gycolide) (PLGA 50:50) by modifying the secondary aqueous phase16.

Pao-Chu Wua et al., 27 The water in soluble polymer ethylcellulose is used as a retardant

prepares sustained release of potassium chloride microspheres by drying in a liquid process.

The effect of sustained release of potassium from ethyl cellulose microspheres was evaluated

by the in vitro dissolution test.

Anne Andre-Abranta et al., 28 Prepared microspheres of ethyl cellulose by solvent

evaporation process. The influence of the agitation rate, the viscosity of the dispersed phase,

the molecular weight of the polymer and the volume ratio between the dispersed phase and

the continuous one on the drug release rate has been studied.

David s et al., 29 study the effects of the process variables, pH of a aqueous phase, rate of

addition of organic, polymeric, drug-containing phase to aqueous phase, organic: aqueous

phase volume ratio and aqueous phase temperature on the entrapment of propraonolol

hydrochloride in ethylcellulose (N4) microspheres prepared by solvent evaporation method

were using factorial design.S.S. Biju et al.,24 Dual coated erodible microcapsules for modified release of diclofenac sodium Diclofenac sodium was formulated as novel enteric microcapsules for improved delivery to the intestine using the polymers cellulose acetate phthalate (CAP) and ethyl cellulose (EC). The novel process was analysed for its capability to produce microcapsules of uniform size, good flowability, uniform drug loading and maximum entrapment efficacy and the absence of interaction between drug and process parameters as well as the polymers. In addition to sustained and uniform release of drug, the best formulation that contained cellulose acetate phthalate and ethyl cellulose in the concentration of 10:90 at 1:1.5 drug–polymer ratio showed better anti-inflammatory activity than the marketed formulation and retarded drug release in the gastric medium.

Drug profile

IUPAC Name: 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol

Chemical Formula : C17H27NO

Molecular Weight : Average-277.4018

1 Drug profile:

Name: Venlafexin

Structure:

Bioavailability: 45%

Protein binding: 27%-30%

Metabolism : Undergoes extensive first pass metabolism in the liver

Half life : 5 hours

Description : white to off white powder

Melting point : 215-217°C

State : solid

Solubility : Slightly soluble

BCS classification: class I (highly solubility highly permeability) Dose : Tablet-100mg,25mg,37.5mg and 50mg capsule-150mg, 37.5mg and 75mg

Pharmacology:

Categories:

Antidepressants

Analgesics

Serotonin Uptake Inhibitors

Antidepressive Agents,

Mechanism of action:

The exact mechanism of action of venlafaxine is unknown, but appears to be

associated with the its potentiation of neurotrasmitter activity in the CNS.

Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the

reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT

than for the NE reuptake process. Both venlafaxine and the ODV metabolite have

weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and

similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-

adrenergic receptors.

AIM AND OBJECTIVE

aIM

To design and Evaluate Micro capsules of Venlafexin

Objective of the study

Venlafaxine is a water soluble drug with a bitter taste. Venlafaxine was used in

the treatment of antidepresent where an ultra rapid onset of action required.

Marketed conventional Venlafaxine formulations are unpleasant, strong bitter taste

and bioavailability is 45% only.

CR formulations that would maintain plasma levels of drug 8 to 15 hrs might be

sufficient for once a day dosing for venlafaxine. CR products are needed for

venlafaxine to prolong its duration of action and to improve patience compliance.

The polymer selected for the present work was Eudragit rs100 and

Eudragit rl 100. The effect of polymer types and drug: polymer ratio on

release also studied. These polymers were sed for controlled release of drugs.

In this formulation method Solvent evaporation method were used for

procuction of micro capsules.

MATERIALS AND METHODS

Materials used

S.N

o

Materials Manufacturer

1 Venlafaxine Reddys labs Ltd,

Hyderabad

2 Eudragit-Rl 100Colorcon Asia Pvt Ltd

3 Eudragit-Rs 100Colorcon Asia Pvt Ltd

S.No Equipments Company

1 Electronic digital balance Shimadzu corp., Japan

2 Double beam UV-

spectrophotometer

Elico pvt India Ltd,

Hyderabad.

3 Dissolution tester ( USP ) Electro Lab TDT-08L

4 Rotary shaker Remi Equipments Ltd

5 Digital vernier calipers Mitutoyo Corp,

Kawasaki,japan

Equipments used

method

Solvent evaporation method were used for procuction of

micro capsules. •Preparation of venlafaxine micro capsule includes first the

polymer of different grades and drug was dissolved in tween80

solvent

•And it is been droped in to sodium carboxy mehyl cellulose (or)

in 0.1 N hydro chloride solution.

EVALUATION TEST

Particle size analysis

Encapsulation efficiency

In-vitro dissolution studies

Morphological study

Differential scanning calorimetric study(DSC)

Fourier transform infrared spectroscopy(FTIR

Results & Discussion

The standard graph of Venlafexine 0.01N HCl

Concentration

(μg/ml)Absorbance

0 0

5 0.148

10 0.271

15 0.385

20 0.478

25 0.604

30 0.721

40 0.944

y = 0.0239x + 0.0098

R2 = 0.9982

0

0.5

1

0 10 20 30 40

Concentration mcg/ml

Ab

so

rba

nc

e (

nm

)

SUMMARY AND CONCLUSION

The prepared microcapsules were spherical and free flowing. The prepared

microcapsules were analyzed for various physico chemical properties such as,

entrapment efficiency, particle size distribution, in vitro dissolution studies,

differential scanning clorimetry, FTIR, scanning electron microscopy.

The entrapment efficiency was increased with the decrease in the polymer content.

Highest proportion of the microcapsules was obtained in the range of 445 μm for

all the formulations.

The drug release form the microcapsules prepared with Eudragit RS 100 was

found between 13 hours and Eudragit RL 100 was found to be 12 hrs The release

kinetics showed that the release was followed first order. The kinetics were best

fitted to the higuchi model clearly indicates that the release mechanism was

diffusion controlled. Peppas n values suggests that the release was Fickian

diffusion.

The spectrum peak points of the formulation were similar with that of the pure

venlafaxine, this clearly indicating that there is no drug polymer interaction.

DSC study was conducted on the pure drug and microcpasules. This clearly

indicates that there is no drug polymer interaction.

The surface of the microcapsule was rough and observed some particles. The

surface was layered and some pores were observed between the layers.

Conclusions

Venlafaxine microcapsules were prepared using various polymers. The results of

drug release kinetics shows first order with diffusion mechanism. The prepared

microcapsules were spherical and free flowing. DSC and FTIR study shows no

drug polymer interaction. This research work gives some preliminary idea about the

release of Venlafaxine embedded in the matrix system as microcapsules.

Refere

nces

[1] http://www.merriam-webster.com/dictionary/microsphere

[2] European pharmacopeia 01/2005, 2 (5) ;909-911.

[3] Ei –Bagory , Ibrahom M, Hosney , E.A.AL- suwaych .s, Mahrous G M effect

of spheres size, polymer to drug ratio and plastisizer concentration on the release

of theophilin from ethyl cellulose microspheres , Saudi pharm Journal,2007; 15;

213-216.

[4] Thanoo BC, Sunny MC and Jayakrishnan A. Cross-linked chitosan

microspheres: Preparation and evaluation as a matrix for the controlled release of

pharmaceuticals. J Pharm Pharmacol. 1992;44:283-286.[5] Gholap SB, Banarjee SK, Gaikwad DD, Jadhav SL and Thorat RM. Hollow microsphere: a review, International Journal of Pharmaceutical Sciences Review and Research. ,2010;1:10-15.[6]Agusundaram M, Madhu Sudana Chetty et al. Microsphere As A Novel Drug Delivery System A Review. International Journal of ChemTech Research. 2009;1(3):526-534.[7] Dr. Fishers Microsphere Selection Bangs laboratories inc, Tech Notes 1-201A

[8] Encyclopedia of pharmaceutical technology, vol.10, 1998, 1-30.

[9] Kavita Kunchu, Raje Veera Ashwani et al. Albumin Microspheres: A Unique

system as drug delivery carriers for non steroidal anti-inflammatory drugs.

2010;5(2):12.

[10] Kalyan Shweta, Sharma Parmod Kumar et al. Recent Advancement InChitosan

Best Formulation And Its Pharmaceutical Application. Pelagia Research Library.

2010;1(3):195-210.

[11] Perumal D. microencapsulation of Ibuprofen and Eudragit RS 100 by

solvent diffusion technology , International journal of pharmaceutics. 2001; 218; 1-

11.

[12] Patrick B O Donnell, James W Mc Ginity , preparation of microspheres by

solvent evaporation technique , Advanced drug delivery review,1998; 28 ; 25-42.

[13] Yie W. Chein, Novel Drug Delivery Systems, Second Edition, Revised and

Expanded, Marcel Dekker, INC. New York, Basel, Hong Kong, 139-196.