FORMULATION AND INVITRO EVALUATION OF

DIP COATED ANTIPARKINSONIAN DRUG

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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 DIP COATING
Dip coating refers to the process in which tablets to
be coated are held in a suitable device
For obtaining more perfect or heavier coats the
dipping and drying steps may be repeated several
times one after another.
 Several dipping arrangements are obtainable,
amongst them the sophisticated devices, which hold
the individual tablets apart until drying is
accomplished, before proceeding to coat additional
tablets or begin recoating cycles.
 STAGES OF DIP COATING

Immersion

Start-up

Deposition

Drainage

Evaporation
 THEORY OF DIP COATING
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substrate to be coated is immersed in a liquid and then withdrawn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

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Self assembly
Sol-gel technique
Layer-by-Layer assembly

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 PARKINSON’S DISEASE
Parkinson's disease (PD also known as idiopathic or
primary parkinsonism, hypokinetic rigid syndrome/HRS,
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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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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 OBJECTIVE
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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 PLAN OF WORK
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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 DRUG PROFILE
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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 MECHANISM OF ACTION
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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 PHARMACODYNAMICS
The form given therapeutically is
therefore a prodrug.
This avoids decarboxylation in the
stomach and periphery, can cross the
blood-brain barrier.
Once in the brain is converted to the
neurotransmitter dopamine by the
enzyme aromatic-L-amino-acid
decarboxylase.
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ABSORPTION:-
Levodopa is rapidly absorbed from the proximal small
intestine by the large neutral amino acid (LNAA) transport
carrier system
BIOAVAILABILITY:- 30%
PROTIEN BINDING:-High about 90%
METABOLISM:-
95% of an administered oral dose of levodopa is pre-
systemically decarboxylated to dopamine by the L-aromatic
amino acid decarboxylase (AAAD) enzyme in the stomach,
lumen of the intestine, kidney, and liver. Levodopa also may
be methoxylated by the hepatic catechol-O-methyltransferase
(COMT) enzyme system to 3-O-methyldopa (3-OMD), which
cannot be converted to central dopamine.

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 BIOTRANSFORMATION
PATHWAY
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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PROPERTIES:-
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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THERAPEUTIC USE
Parkinson’s disease and dopamine-responsive
dystonia.

DRUG INTERACTIONS
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.
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 SIDE EFFECTS
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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 MATERIALS USED
LEVODOPA
DL-METHIONINE
LACTOSE
EUDRAGIT 100M
AEROSIL
PRE-GELATINISED MAIZE STARCH
MAGNESIUM STERATE
TALC
SODIUM STARCH GLYCOLATE
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 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 weighed
individally. The average weight is calculated and
the individual weights are compared with
average.
B. Hardness: It is tested mainly by using monsanto
hardness tester.The hardness of sustained
relase tablets should be in between 5-6 Kg/cm2.
C. Friability:It is tested mainly by using Roche
friabilator.They are placed in friabilator and
operated for 100 revolutions at 25 rpm.
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 EVALUATION :-
D. Dissolution:
Dissolution rates studies were studied in phosphate buffer
of Ph:6.8 by using 6 basket dissolution apparatus with
paddle as a stirrer at 50 rpm at a temperature of 37 ± 1OC
maintained through out this study.
Each tablet containing 150 mg of levodopa was used.
From each basket, sample of dissolution media (5ml) is
withdrawn through at different intervals of time, suitably
filtered, diluted and assayed at wavelength (λ max) 280 nm for
levodopa.
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:-
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.

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 REFERENCES:-
Dip coating-LACHMAN AND LIEBERMAN-theory and practice of
industrial pharmacy
 Kathrynne Holden. " Levodopa, and Parkinson's Disease". Retrieved
Sep 30, 2013.
 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.
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