32
By:- G. TARUN KUMAR REDDY B.pharm., “FORMULATION AND EVALUATION OF PROLONGED RELEASE OF METFORMIN HYDROCHLORIDE TABLETS”

Metformin hydrochloride

Embed Size (px)

Citation preview

Page 1: Metformin hydrochloride

By:- G. TARUN KUMAR REDDY B.pharm.,

“FORMULATION AND EVALUATION OF PROLONGED

RELEASE OF

METFORMIN HYDROCHLORIDE TABLETS”

Page 2: Metformin hydrochloride

INTRODUCTION:-

\ The drug delivery systems are those which control the rate of drug delivery, sustaining the duration of therapeutic activity and targeting the drug to the diseased tissue.

Thereby leading the better therapeutic effect with minimum side effects. The different types of drug delivery systems are as follows:-

ORAL CONTROLLED

TRANSDERMAL

MUCOADHESIVE TARGETED

DRUG DELIVERY SYSTEMS

Page 3: Metformin hydrochloride

EXTENDED RELEASE TABLETS

The medical advances have been made in the area of drug delivery with the development of novel dosage forms.

The area of sustained drug delivery has granted as the most promising type of the drug delivery system.

The sustained release or extended release drug delivery system can be solve problems concerning the targeting of a drug to a specific organ or tissue.

The extended release tablets will provide controlling the rate of drug delivery.

Page 4: Metformin hydrochloride

The terms used for extended release tablets are:-

EXTENDED RELEASE TABLETS

DELAYEDRELEASE TABLETS

PROLONGEDRELEASE TABLETS

SUSTAINED RELEASE TABLETS

CONTROLLED RELEASE TABLETS

Page 5: Metformin hydrochloride

ADVANTAGES:-

1. Enhance product saftey.2. Improved Efficacy.3. Improved patient compliance.4. More accurate compared to other conventional drug delivery systems. DISADVANTAGES:-

1. Stabilty Problems.2. Expensive.3. May Alter With The Food.

Page 6: Metformin hydrochloride

PHYSICOCHEMICAL PROPERTIES:

IUPAC Name : N,N-Dimethyl imidodicarbonimidic diamide

DRUG PROFILE

Appearance White or almost white crystalline Powder

Solubility Soluble in water Freely soluble as HCl salt

Molecular formula C4H11N5

Molar mass 129.16 g mol−1

log P 1.254

State Solid

Melting point 223-226 oC

pKa 12.4

BCS CLASSIFICATION Class-III

Page 7: Metformin hydrochloride

MECHANISM OF ACTION

Page 8: Metformin hydrochloride

LITERATURE REVIEW

•David P Figgitt et al., The purpose of this research was to formulate and characterize solid dispersion (SD) of metformin hydrochloride using methocel K100M as the carrier by the solvent evaporation and cog-rinding method.

Characterization was performed by Fourier transform spectroscopy (FTIR), ultraviolet,

The optimized formulation was subjected to accelerated stability testing as per ICH guidelines.

•Basavaraj.k Nanjwade et al., To develop and characterize an oral Prolonged-release matrix tablet of metformin hydrochloride using a combination of a hydrophobic carrier and hydrophilic polymer and two types of formulation techniques.

Page 9: Metformin hydrochloride

P. K. Bhoyar et al ., An attempt was made to sustain the release of metformin HCl as well as to mask the bitter taste by complexation technique using strong cation-exchange resins.

The drug loading into ion-exchange resin was optimized for mixing time, activation, effect of pH, mode of mixing, ratio of drug:resin and temperature.

The resinate was evaluated for micromeritic properties, taste masking and characterized using IR. Using resinate sustained release tablets were.

Page 10: Metformin hydrochloride

AIM Formulation and evaluation of prolonged release of Metformin

Hydrochloride Tablets. OBJECTIVE

Under these considerations, objective of the work is

To design the formula for Metformin Hcl ER tablets.

To incorporate selected model drug candidates in the same formula and prepare tablets.

To evaluate the prepared tablets of Metformin hydrochloride.

To study the in-vitro dissolution profile of prepared tablets.

Stability evaluation studies were carried out.

Page 11: Metformin hydrochloride

PLAN OF WORK

Preformulation studies :-

*API characterization   *Organoleptic evaluation   *Solubility   *Analytical evaluation   *Bulk density   *Tapped density   *Angle of repose   *Compressibility index    

Page 12: Metformin hydrochloride

Evaluation Of Tablets Post Formulation Studies:- Hardness

Uniformity of thickness

Friability

Weight variation

Content uniformity

In vitro dissolution Stability studies.

Page 13: Metformin hydrochloride

Extented release tablets containing 500 mg of model drug were prepared with a total tablet weight of 750mg.

Considering the pre-formulation studies and the literature survey conducted the excipients were selected and an attempt to produce prolonged released tablets.

FORMULATION AND

DEVELOPMENT

Page 14: Metformin hydrochloride

Add the lubricant (magnesium stearate)

COMPRESSS the blend for tablet formation

PASS THROUGH SIEVE (No:-40)

DIRECT COMPRESSION METHODMETFORMIN BINDER(POVIDONE)+

ADD DILUENT

Page 15: Metformin hydrochloride

METHOD:

1. The powder blend is subjected to drying and was compressed by direct compression method by using Standard concave punches in 8 Station Kambet KMPC8 tablet punching machine

2. Punches of 17.5mm and 7mm diameter were used for compression.

3. Tablet of 748mg and 753mg was prepared in different trials by adjusting hardness and volume screw of compression machine properly.

Page 16: Metformin hydrochloride

WET GRANULATION METHOD

Drug + polymerPass through sieve No:- 40

Add Diluent , half part of binder Then Pass through sieve(sieve No.40)DM water

Prepare granules and lubricated itwith Magnesium sterate (pre-sifted through sieve No. 60) mix 5 minutes

Subject the blend for tablet formulation (compression)

Page 17: Metformin hydrochloride

• METHOD:-

Compress with punches in 8 Station Kambet KMPC8 tablet punching machine.

Standard concave punches of 17.5mm, with breakline punches measuring the Tablet of750mg,770mg,740mg and 760mg was prepared in different trials by adjusting hardness and volume screw of compression machine properly.

Page 18: Metformin hydrochloride

DEVELOPMENT OF METFORMIN OF PROLONGED RELEASE TABLETS

Formula

INGREDIENTS Mg/Tab(T1)

API 500

Polyox-303 50

Lactose monohydrate 190

Mg Stearate 10

Total Weight 750

Page 19: Metformin hydrochloride

PRE-FORMULATION OF API

I. Pre Compression Parameters1.Angle of Repose

The angle of repose has been used to characterize the flow properties of solids.

This is the maximum angle possible between surface of pile of powder or granules and the horizontal plane.

It was calculated using the following equation:- Tanθ = h / r θ = tan –1 h / r   Where, h = height of the powder heap r = radius of the powder heap θ= angle of repose

Page 20: Metformin hydrochloride

2.Bulk density:

Bulk density defined as the mass of many particles of the material divided by the total volume they occupy.

The total volume includes particle volume, inter-particle void volume, and internal pore volume.

Bulk density is not an intrinsic property of a material.

Bulk density = Weight of powder(g) / Bulk volume(ml)

Page 21: Metformin hydrochloride

3.Tapped density:-

Tapped densitiy of the drug was determined by pouring 25 gm through a glass funnel into a 100 ml cylinder.

The cylinder was tapped from height of 2 inches until a constant volume was obtained.

The volume occupied by the sample after tappings were recorded and the tapped density was calculated by the formula below

Tapped density = Weight of powder(g) / Tapped volume(ml)

Page 22: Metformin hydrochloride

4.Carr’s compressibility index:-

Compressibility is the ability of powder to decrease in volume under pressure.

It is one of the method to determine the flow properties by comparing the bulk and tapped densities.

% Compressibility Flow description

<10 Excellent

11-15 Good

16-20 Fair

21-25 Passable

26-31 Poor

32-37 Very poor

>38 Extremely poor

Page 23: Metformin hydrochloride

Carr’s index of each formulation was calculated according to equation given below:-

Tapped density – Bulk density

Tapped density X 100Carr’s index =

Page 24: Metformin hydrochloride

II. Post- compression parameters:The quantitative evaluation of a tablet’s chemical, physical and

bioavailability properties are important in the design of tablets and to monitor product quality.

• General appearance:-The general appearance of tablets, its visual identity is essential

for consumer acceptance, control of lot-to-lot uniformity and general tablet-to-tablet uniformity.

The control of general appearance involves measurement attributes such as

Tablet’s sizeShapeColor

Presence or absence of odourTaste

Surface textures & etc.

Page 25: Metformin hydrochloride

• Hardness or crushing strength:-

The resistance of tablets to capping, abrasion or breakage under conditions of storage, transportation and handling before usage depends on its hardness.

It is measured either by Monsanto or Stokes hardness tester, by applying pressure diametrally to the tablet.

Monsanto Hardness Tester

Page 26: Metformin hydrochloride

RESULT IDENTIFICATION OF DRUG:

By UV Spectroscopy:Determination of max of Anti hyperglycemic agent:

On the basis of preliminary identification test the drug scanned and it was concluded that the drug had max of 232 nm

which was equal to max 232nm as reported (std.).SPECTRUM POINT PICK METHOD

Page 27: Metformin hydrochloride

STABILITY STUDIESThe stability studies were carried out by storing in HDPE containers under the

Accelerated stability conditions of 40ºC /70% RH for a period of 1 month.

The tablets were evaluated for the parameters like weight variation, hardness, friability, thickness, and percentage of drug content were evaluated for initial, 1st, 2nd, 3rd and 1month.

The tablets displayed all parameters of optimized formulation F10 within specified limits indicating the stability of the formulation.

Parameters 1st week 2nd week 3rd week 4th week

Weight variation (mg) 750±5 750±4 750±4 750±4

Thickness (mm) 5.75±0.6 5.75±0.7 5.75±0.7 5.74±0.6

Hardness (N) 180 ± 10 190 ± 10 185±10 180 ± 20

Friability (%) 0.045 0.15 0.15 0.015

Drug Content (%) 97 96 95 94

Stability Studies Of Metformin Prolonged Release Tablets

Page 28: Metformin hydrochloride

Stability Effect On In-Vitro Dissolution Of Optimized Formulation (F10) at 1,2,3&4 week.

Time (Hours)% Drug Release

1st week 2nd week 3rd week 4th week0 0 0 0 01 30 25 28 272 42 40 39 443 54 54 52 536 76 773 74 74

10 98 96 96 95

Stability Effect On In Vitro Drug release profile of Trial-10

Page 29: Metformin hydrochloride

BIBLIOGRAPHY•United States pharmacopoeia (2008) Bulk density and tapped density, Carr’s index and Hausner’s ratio, USPNF 2008, vol-1, page no: 231-232.

•Indian Pharmacopoeia (2012) Uniformity of weight of single dose preparations, Friability, 2010, vol-1, page no: 140, 192-193.

• Lachman L. and Lieberman H.A., Pharmaceutical Dosage Forms, In; Tablets, Vol. 2, Marcel Dekker, Inc., New York ,1989 pp.367-414 •Martin,A.; Physical pharmacy; Fourth edition ; PP 444-445. •www.wikipedia.org/wiki/tablets

• www.pharmainfo.net/tablets/types-tablets Remington The Science and Practice of Pharmacy, 21st edition Vol.-1, Page No.1178-1198

• www.Drugbank.com

Page 30: Metformin hydrochloride

•Brahmankar D.M., Jaiswal S.B., “Biopharmaceutics & Pharmacokinetics”; First Edition; p-335 (1995).

•Tripathi KD, Essential of medical pharmacology, 5th ed.New Delhi: Jaypeebrothepublishing house;2003, 254-275.

• United States pharmacopoeia (2012) Bulk density and tapped density, Carr’s index and Hausner’s ratio, USPNF 2008, vol-1, page no: 231-232.

•Indian Pharmacopoeia (2012) Uniformity of weight of single dose preparations, Friability, 2010, vol-1, page no: 140, 192-193.

•British Pharmacopoeia (2012) Angle of repose, vol-5, Appendix-A465.

Page 31: Metformin hydrochloride

•http://www.researchwikis.com/Generics_Market_Analysis_Marketing_ Research.

•United States pharmacopoeia (2012) Bulk density and tapped density, Carr’s index and Hausner’s ratio, USPNF 2008, vol-1, page no: 231-232.

Page 32: Metformin hydrochloride