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.

DIP COATING

Dip coating refers to the process in which tablets to be coated are held in a suitable deviceFor 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

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Dip coating techniques can be described as a process where the substrate to be coated is immersed in a liquid and then withdrawn with a well-defined withdrawal speed under controlled temperature and atmospheric conditions.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 assemblySol-gel techniqueLayer-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

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 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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PHARMACODYNAMICS

Levodopa is rapidly absorbed from the proximal small intestine by the large neutral amino acid (LNAA) transport carrier 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-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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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.

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THERAPEUTIC USE

DRUG INTERACTIONS

Parkinson’s disease and dopamine-responsive dystonia.

Hypotension Arrhythmias NauseaGastrointestinal bleeding Disturbed  respiration,Hair lossDisorienation and confusion Extreme emotional states,Anxiety Excessive libido Vivid dreams or insomnia Auditory or visual hallucinations Somnolence and narcolepsyStimulant psychosis

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SIDE EFFECTS

MATERIALS USED

LEVODOPA DL-METHIONINE LACTOSE EUDRAGIT 100MAEROSIL PRE-GELATINISED MAIZE STARCH MAGNESIUM STERATE TALC SODIUM STARCH GLYCOLATE

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METHODOLOGY:-Method of preparation is by wet granulationGRANULATION:

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 stearateTalcAerosilThen 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:-

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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 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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