FORMULATION AND INVITRO EVALUATION OF DIP COATED ANTIPARKINSONIAN DRUG 1 Presented by SHAHEEN BEGUM UNDER THE GUIDANCE OF Associate Professor. Syed Mohammed Kazim Nizam Institute of Pharmacy & Research Centre Deshmukhi (V), Nalgonda. AFFILIATED TO JNTUH.
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FORMULATION AND INVITRO EVALUATION OF
DIP COATED ANTIPARKINSONIAN DRUG
1
Presented by
SHAHEEN BEGUMUNDER THE GUIDANCE OF
Associate Professor. Syed Mohammed KazimNizam Institute of Pharmacy & Research Centre
Deshmukhi (V), Nalgonda.AFFILIATED TO JNTUH.
DIP COATING
Dip coating refers to the process in which tablets tobe coated are held in a suitable device
For obtaining more perfect or heavier coats thedipping and drying steps may be repeated severaltimes one after another.
Several dipping arrangements are obtainable,amongst them the sophisticated devices, which holdthe individual tablets apart until drying isaccomplished, before proceeding to coat additionaltablets or begin recoating cycles.
STAGES OF DIP COATING
Immersion
Start-up
Deposition
Drainage
Evaporation
THEORY OF DIP COATING
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Dip coating techniques can be described as a process where the
substrate to be coated is immersed in a liquid and then withdrawn
with a well-defined withdrawal speed under controlled temperature
and atmospheric conditions.
Fig. 1:Stages of the dip coating process: dipping of the substrate into the
coating solution, wet layer formation by withdrawing the substrate and
gelation of the layer by solvent evaporation
Self assembly
Sol-gel technique
Layer-by-Layer assembly
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Parkinson's disease (PD also known as idiopathic or
or paralysis agitans) is a degenerative disorder of the central
nervous system.
Early in the course of the disease, the most obvious
symptoms are movement-related; these
include shaking, rigidity, slowness of movement and
difficulty with walking and gait.
The main motor symptoms are collectively
called parkinsonism, or a "parkinsonian syndrome".
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PARKINSON’S DISEASE
The pathology of the disease is characterized by the
accumulation of a protein called
alphasynuclein into inclusions called lewy bodies in
neurons, and from insufficient formation and activity
of dopamine produced in certain newrons within parts of
the midbrain.
Modern treatments are effective at managing the early
motor symptoms of the disease, mainly through the use
of levodopa and dopamine agonists.
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The aim and objective of this study was to develop and
evaluate a dip coated sustained release coated tablet that
is stable for an extended period of time.The polymers
prevent the degradation of drug in the acidic environment
of the stomach.
Levodopa is used as a model drug. This system
consisted of a 10mm tablet prepared by wet granulation
method and subsequent compression and coated with
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OBJECTIVE
Survey of literature.
Selection of drug.
Selection of suitable polymers.
Selection of suitable technique.
Tablet preparation.
Dip coating.
Evaluation parameters.
Hardness test.
Friability test.
Weight variation.
Dissolution test.
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PLAN OF WORK
L-DOPA (L-3,4-dihydroxyphenylalanine) is a chemical that
is made and used as part of the normal biology of humans,
some animals and plants.
Some animals and humans make it via biosynthesis from
the amino acid L-Tyrosine.
L-DOPA is the Precursor to the neurotransmitters
dopamine, norepinephrine (noradrenaline), and
epinephrine (adrenaline) collectively known
as catecholamine.
As a drug it is used in the clinical treatment of parkinson’s
disease and dopamine-responsive dystonia.
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DRUG PROFILE
Striatal dopamine levels in symptomatic
Parkinson's disease are decreased by 60 to 80%.
A small percentage of each levodopa dose
crosses the blood-brain barrier and is
decarboxylated to dopamine.
This newly formed dopamine then is available
to stimulate dopaminergic receptors, thus
compensating for the depleted supply of
endogenous dopamine.
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MECHANISM OF ACTION
The form given therapeutically istherefore a prodrug.
This avoids decarboxylation in thestomach and periphery, can cross theblood-brain barrier.
Once in the brain is converted to theneurotransmitter dopamine by theenzyme aromatic-L-amino-aciddecarboxylase.
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PHARMACODYNAMICS
Levodopa is rapidly absorbed from the proximal smallintestine by the large neutral amino acid (LNAA) transportcarrier systemBIOAVAILABILITY:- 30%
PROTIEN BINDING:-High about 90%
METABOLISM:-
95% of an administered oral dose of levodopa is pre-systemically decarboxylated to dopamine by the L-aromaticamino acid decarboxylase (AAAD) enzyme in the stomach,lumen of the intestine, kidney, and liver. Levodopa also maybe methoxylated by the hepatic catechol-O-methyltransferase(COMT) enzyme system to 3-O-methyldopa (3-OMD), whichcannot be converted to central dopamine.
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ABSORPTION:-
Levodopa can be directly metabolized by catechol-o-methyl
transferase[COMT] to 3-o-methyl dopa [3-OMD] and then further
to homo vanillic acid [HMV]
HALF LIFE:-50 to 90 minutes
EXCRETION:-
Through renal 60-70%
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BIOTRANSFORMATION
PATHWAY
MELTING POINT:- 285 Degrees C
SOLUBILITY:- slightly soluble in water,soluble in aqueous
solutions of mineral acids and alkali,practically insoluble in
alcohol,chlororform and ether.
SHELF LIFE:-at least of 5 years
STORAGE CONDITIONS:-store in dry place and prevent
exposure to excessive heat and light store in air tight containers at a
temperature not exceeding 40 degrees.
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PROPERTIES:-
This medication should not be taken if you
are taking MAOIs (e.g., furazolidone,
phenelzine, selegiline, tranylcypromine).
Persons taking levodopa should not take
vitamin B6 (pyridoxine) since this vitamin can
reduce levodopa's effects.17
THERAPEUTIC USE
DRUG INTERACTIONS
Parkinson’s disease and dopamine-responsive dystonia.
Hypotension
Arrhythmias
Nausea
Gastrointestinal bleeding
Disturbed respiration,
Hair loss
Disorienation and confusion
Extreme emotional states,
Anxiety
Excessive libido
Vivid dreams or insomnia
Auditory or visual hallucinations
Somnolence and narcolepsy
Stimulant psychosis
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SIDE EFFECTS
MATERIALS USED
LEVODOPA
DL-METHIONINE
LACTOSE
EUDRAGIT 100M
AEROSIL
PRE-GELATINISED MAIZE STARCH
MAGNESIUM STERATE
TALC
SODIUM STARCH GLYCOLATE 19
METHODOLOGY:-Method of preparation is by wet granulation
GRANULATION:
All the above ingredients are weighed accurately and mixed well in a mortar and pestle.
Mean while a 3% solution of povidone is prepared in water .
This mixture is heated to allow proper mixing of povidone with water.
This hot solution is slowly poured in the mortar containing the above ingrediets and a dough is prepared.
Now granules are prepared by passing the dough through seive no 16.
The granules are dried in an oven at 40ᵒC for 30 minutes.
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METHODOLOGY:-COMPRESSION
The dried granules are thoroughly mixed with
Magnesium stearate
Talc
Aerosil
Then these are compressed in a tablet compression machine.
The size of the die was 10mm.
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METHODOLOGY:-
COATING The dip coating solution is prepared by mixing hydroxy propyl methyl cellulose and starch soluble .
To the above mixture isopropyl alcohol is added in sufficient quantity to prepare a solution.
Now the compressed tablets are coated with this solution.
Note that the cycles of coating can be repeated to obtain desired thickness but the primary coating should be dried efficiently before the next coating begins.
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EVALUATION :-
A. Weight variation : 20 tablets are weighedindividally. The average weight is calculated andthe individual weights are compared withaverage.
B. Hardness: It is tested mainly by using monsantohardness tester.The hardness of sustainedrelase tablets should be in between 5-6 Kg/cm2.
C. Friability:It is tested mainly by using Rochefriabilator.They are placed in friabilator andoperated for 100 revolutions at 25 rpm.
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EVALUATION :-D. Dissolution:
Dissolution rates studies were studied in phosphate bufferof Ph:6.8 by using 6 basket dissolution apparatus withpaddle as a stirrer at 50 rpm at a temperature of 37 ± 1OCmaintained through out this study.
Each tablet containing 150 mg of levodopa was used.
From each basket, sample of dissolution media (5ml) iswithdrawn through at different intervals of time, suitablyfiltered, diluted and assayed at wavelength (λ max) 280 nm forlevodopa.
The sample of dissolution fluid were replaced with fresh fluid.
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Graph of of Comparision of release rates levodopa marketed and dipcoated sustained release tablet.
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CONCLUSION:-
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From the above work we can conclude that levodopa dipcoated sustained release tablets are superior than the conventional levodopa tablets.Sustained release dosage forms follows first order kinetics hence the drug is released at a sustained peroiod of time. Also the drug stays for longer time in the therapeutic range.DL-Methionine which was incorporated in the formulation also released which acts as hepatoprotective.Levodopa dipcoated sustained release tablets were evaluated for their physical properties. The results showed that the average weight, hardness and friability of the drug were compatible with the standards prescribed.
REFERENCES:-
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Dip coating-LACHMAN AND LIEBERMAN-theory and practice of industrial pharmacy
Merims D, Giladi N (2008). "Dopamine dysregulation syndrome, addiction and behavioral changes in Parkinson's disease".
Basma AN, Morris EJ, Nicklas WJ, Geller HM (February 1995). "L-dopa cytotoxicity to PC12 cells in culture is via its autoxidation". Journal of Neurochemistry 64 (2): 825–32.
Cotzias, GC, Papavasiliou, PS, Gellene, R (1969). "L-dopa in parkinson's syndrome".The New England Journal of Medicine 281 (5): 272.
Linko, P (1982), "Lactose and Lactitol", in Birch, G.G. & Parker, K.J, Natural Sweeteners, London & New Jersey: Applied Science Publishers, pp. 109–132.
"Nomenclature and symbolism for amino acids and peptides (IUPAC-IUB Recommendations 1983)", Pure Appl. Chem. 56 (5), 1984: 595–624.