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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

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Presented by

SHAHEEN BEGUMUNDER THE GUIDANCE OF

Associate Professor. Syed Mohammed KazimNizam 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 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.

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STAGES OF DIP COATING

Immersion

Start-up

Deposition

Drainage

Evaporation

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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substrate to be coated is immersed in a liquid and then withdrawn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

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Self assembly

Sol-gel technique

Layer-by-Layer assembly

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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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PARKINSON’S DISEASE

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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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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

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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

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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

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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

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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

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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:-

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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

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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:-

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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.

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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

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MATERIALS USED

LEVODOPA

DL-METHIONINE

LACTOSE

EUDRAGIT 100M

AEROSIL

PRE-GELATINISED MAIZE STARCH

MAGNESIUM STERATE

TALC

SODIUM STARCH GLYCOLATE 19

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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 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.

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REFERENCES:-

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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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