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By:- G. TARUN KUMAR REDDY B.pharm.,
“FORMULATION AND EVALUATION OF PROLONGED
RELEASE OF
METFORMIN HYDROCHLORIDE TABLETS”
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
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.
The terms used for extended release tablets are:-
EXTENDED RELEASE TABLETS
DELAYEDRELEASE TABLETS
PROLONGEDRELEASE TABLETS
SUSTAINED RELEASE TABLETS
CONTROLLED RELEASE TABLETS
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.
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
MECHANISM OF ACTION
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.
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.
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.
PLAN OF WORK
Preformulation studies :-
*API characterization *Organoleptic evaluation *Solubility *Analytical evaluation *Bulk density *Tapped density *Angle of repose *Compressibility index
Evaluation Of Tablets Post Formulation Studies:- Hardness
Uniformity of thickness
Friability
Weight variation
Content uniformity
In vitro dissolution Stability studies.
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
Add the lubricant (magnesium stearate)
COMPRESSS the blend for tablet formation
PASS THROUGH SIEVE (No:-40)
DIRECT COMPRESSION METHODMETFORMIN BINDER(POVIDONE)+
ADD DILUENT
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.
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)
• 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.
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
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
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)
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)
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
Carr’s index of each formulation was calculated according to equation given below:-
Tapped density – Bulk density
Tapped density X 100Carr’s index =
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.
• 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
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
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
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
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
•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.
•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.