CASE STUDY OF THE MOLECULE -Made By: KEVAL DALSANIYA -Enroll. No.: Branch: CHEMICAL (2 nd year)

ABSTRACT Project mainly contains the process or preparation of a molecule ( mainly drug molecule), named as Levocetirizine Dihydrochloride. ( mainly drug molecule), named as Levocetirizine Dihydrochloride. It is an orally active H1-receptor antagonist. The preparation process includes mainly 3-stages/steps. The final product is mainly obtained after the continuous process of days. of days. There are various forms of product like 5 mg tablets, 500 mg tablets, 0.5 mg oral solution. tablets, 0.5 mg oral solution.

INTRODUCTION Levocetirizine dihydrochloride, the active component of XYZAL tablets and oral solution, is an orally active H1-receptor antagonist. Levocetirizine dihydrochloride, the active component of XYZAL tablets and oral solution, is an orally active H1-receptor antagonist. The chemical name is (R)-[2-[4-[(4-chlorophenyl) phenylmethyl]-1-piperazinyl] ethoxy] acetic acid dihydrochloride. The chemical name is (R)-[2-[4-[(4-chlorophenyl) phenylmethyl]-1-piperazinyl] ethoxy] acetic acid dihydrochloride. Levocetirizine dihydrochloride is the R enantiomer of cetirizine hydrochloride, a racemic compound with antihistaminic properties. Levocetirizine dihydrochloride is the R enantiomer of cetirizine hydrochloride, a racemic compound with antihistaminic properties. The empirical formula of levocetirizine dihydrochloride is C 21 H 25 ClN 2 O 3 2HCl. The molecular weight is and the chemical structure is shown below: The empirical formula of levocetirizine dihydrochloride is C 21 H 25 ClN 2 O 3 2HCl. The molecular weight is and the chemical structure is shown below: Levocetirizine dihydrochloride is a white, crystalline powder and is water soluble. Levocetirizine dihydrochloride is a white, crystalline powder and is water soluble.

XYZAL 5 mg tablets are formulated as immediate release, white, film- coated, oval-shaped scored tablets for oral administration. The tablets are imprinted on both halves of the scored line with the letter Y in red (Opacode®Red). Inactive ingredients are: microcrystalline cellulose, lactose monohydrate, colloidal anhydrous silica, and magnesium stearate. The film coating contains hypromellose, titanium dioxide, and macrogol 400. XYZAL 5 mg tablets are formulated as immediate release, white, film- coated, oval-shaped scored tablets for oral administration. The tablets are imprinted on both halves of the scored line with the letter Y in red (Opacode®Red). Inactive ingredients are: microcrystalline cellulose, lactose monohydrate, colloidal anhydrous silica, and magnesium stearate. The film coating contains hypromellose, titanium dioxide, and macrogol 400. XYZAL 0.5 mg/mL oral solution is formulated as an immediate release, clear, colorless liquid. Inactive ingredients are: sodium acetate trihydrate, glacial acetic acid, maltitol solution, glycerin, methylparaben, propylparaben, saccharin, flavoring (consisting of triacetin, natural & artificial flavors, dl-alpha-tocopherol), purified water. XYZAL 0.5 mg/mL oral solution is formulated as an immediate release, clear, colorless liquid. Inactive ingredients are: sodium acetate trihydrate, glacial acetic acid, maltitol solution, glycerin, methylparaben, propylparaben, saccharin, flavoring (consisting of triacetin, natural & artificial flavors, dl-alpha-tocopherol), purified water.

SMALL SCALE PREPARATIONS

PROPERTIES 【 Appearance 】 【 Appearance 】 white or off-white crystalline powder white or off-white crystalline powder 【 Melting Point 】 【 Melting Point 】 ℃ ℃ 【 Boiling Point 】 【 Boiling Point 】 °C at 760 mmHg °C at 760 mmHg 【 Flash Point 】 【 Flash Point 】 °C °C

LARGE SCALE PREPARATION Brief manufacturing process: Brief manufacturing process: Stage-1 : Stage-1 : (R)-1-((4-chlorophenyl)(phenyl)methyl)piperazineis react with 2- Chloro ethanol in presence of toluene and Triethyl amine at 25 ± 5°C temperature. Reaction mass cool to 60 ± 2 °C. Add water into reaction mass at 60 ± 2 °C. Separate the both layers. Take organic layer and add water. pH adjusted to 1.5 to 2.0 of reaction mass by hydrochloric acid. Separate both layer. Add toluene in aqueous layer and adjust pH 10.0 to 12.0 by caustic lye. Extract product in toluene. Distill out toluene under vacuum temperature up to 80 °C. Charge Dimethyl formamide and unload the reaction mass at 30 ± 5 °C. (R)-1-((4-chlorophenyl)(phenyl)methyl)piperazineis react with 2- Chloro ethanol in presence of toluene and Triethyl amine at 25 ± 5°C temperature. Reaction mass cool to 60 ± 2 °C. Add water into reaction mass at 60 ± 2 °C. Separate the both layers. Take organic layer and add water. pH adjusted to 1.5 to 2.0 of reaction mass by hydrochloric acid. Separate both layer. Add toluene in aqueous layer and adjust pH 10.0 to 12.0 by caustic lye. Extract product in toluene. Distill out toluene under vacuum temperature up to 80 °C. Charge Dimethyl formamide and unload the reaction mass at 30 ± 5 °C.

Stage-2 : Stage-2 : (R)-2-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethanol (Stage-1) and dimethyl formamide solution cool to 17 ± 3 °C. Add Potassium hydroxide at 17 ± 3 °C and further cool up to 11 ± 1 °C. Add sodium mono chloro acetate at 11 ± 1 °C. Raise reaction mass temperature up to 38 °C. Add water and adjust reaction mass pH 7.5 to 8.0 by Hydrochloric acid solution (1:1). Wash reaction mass with toluene at 32 ± 3°C. Aqueous layer is charcoalized and filter. Extract product in methylene dichloride at 30 ± 5°C. Add water in methylene chloride layer and pH adjusted to 4.0 to 4.5 by hydrochloric acid (1:1). Separate organic layer and distill out methylene dichloride up to 75 °C under vacuum. Give toluene striping to residue. Add acetone in residue. charcoalised and filter. Purge HCl gas into clear filtrate at 25 ± 5°C. Centrifuge the product and wash with acetone to get Levocetirizine dihydrochloride (technical). (R)-2-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethanol (Stage-1) and dimethyl formamide solution cool to 17 ± 3 °C. Add Potassium hydroxide at 17 ± 3 °C and further cool up to 11 ± 1 °C. Add sodium mono chloro acetate at 11 ± 1 °C. Raise reaction mass temperature up to 38 °C. Add water and adjust reaction mass pH 7.5 to 8.0 by Hydrochloric acid solution (1:1). Wash reaction mass with toluene at 32 ± 3°C. Aqueous layer is charcoalized and filter. Extract product in methylene dichloride at 30 ± 5°C. Add water in methylene chloride layer and pH adjusted to 4.0 to 4.5 by hydrochloric acid (1:1). Separate organic layer and distill out methylene dichloride up to 75 °C under vacuum. Give toluene striping to residue. Add acetone in residue. charcoalised and filter. Purge HCl gas into clear filtrate at 25 ± 5°C. Centrifuge the product and wash with acetone to get Levocetirizine dihydrochloride (technical). Stage-3 : Stage-3 : Technical Levocetirizine dihydrochloride charged into acetic acid. Reaction mass heated to 82 ± 3°C to get clear solution. Reaction mass cool to 55 ± 5 °C. Add acetone at 55 ± 5 °C. Cool reaction mass to 30 ± 5 °C. Centrifuge the product and wash with acetone to get Levocetirizine dihydrochloride API. Technical Levocetirizine dihydrochloride charged into acetic acid. Reaction mass heated to 82 ± 3°C to get clear solution. Reaction mass cool to 55 ± 5 °C. Add acetone at 55 ± 5 °C. Cool reaction mass to 30 ± 5 °C. Centrifuge the product and wash with acetone to get Levocetirizine dihydrochloride API.

Route of Synthesis :

Process Flow Diagram Stage : 1Stage : 2

Stage : 3

Cooling Tower Scrubber

USES Levocetirizine is an antihistamine used to relieve allergy symptoms such as watery eyes, runny nose, itching eyes/nose, symptoms such as watery eyes, runny nose, itching eyes/nose, sneezing, hives, and itching. It works by blocking a certain sneezing, hives, and itching. It works by blocking a certain natural substance (histamine) that your body makes during an natural substance (histamine) that your body makes during an allergic reaction. allergic reaction. SIDE EFFECTS Levocetirizine is called a non-sedating antihistamine as it does not enter the brain in significant amounts, and is therefore unlikely to cause drowsiness. However, some people may experience some slight sleepiness, headache, mouth dryness, lightheadedness, vision problems (mainly blurred vision), palpitations and fatigue.

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