Pharmaceutical Technology-I Lab MANIK

Laboratory Manual

Course Code: 3126

Course Title: Pharmaceutical Technology-I Lab

Md. Imran Nur Manik Ph.G.; M.Pharm (Thesis) (RU)

Lecturer

Department of Pharmacy

Northern University Bangladesh

ACKNOWLEDGEMENT

Laboratory Manual: Pharmaceutical Technology-I Lab Page i Comprehensible Composition By: Md. Imran Nur Manik; Ph.G. ; M.Pharm. (Thesis)

All the praise goes to ALLAH SUBHANAHU WA’TALA the most الحمد لله رب عالمين

gracious ,the most merciful.

I would like to express my best regards, and

appreciation to Prof. Dr. Md. Harun Ar Rashid, PhD

(Pharm. Tech.), University of Helsinki, Finland,

M. Pharm.University of Dhaka, B. Pharm. University

of Dhaka, Head department of Pharmacy, Nortern

University Bangladesh, for his expert guidance and

enthusiastic encouragement throughout the entire

period of this work.

I convey my heartiest thanks to Mariam Begum;

Principal Lab Demonstrator, Department of

Pharmacy; Northern University Bangladesh, for her

kind co-operation.

I would like to express my sincere gratitude to all of my collegues especially

Sushanta Halder and Shadiduzzaman; Lecturer, Department of Pharmacy,

Northern University Bangladesh, for their encouragement and kind support.

Author

January, 2018 Md. Imran Nur Manik

Head, Department of Pharmacy Northern University Bangladesh

Md. Imran Nur Manik

TABLE OF CONTENTS

Laboratory Manual: Pharmaceutical Technology-I Lab Page ii Comprehensible Composition By: Md. Imran Nur Manik; Ph.G. ; M.Pharm. (Thesis)

Sl.

No. Date Name of the experiment

Page

No.

01. Formulation and preparation of pediatric paracetamol oral solution.

(Each 5 mL contains Paracetamol BP 120 mg) 01 – 05

02. Formulation and preparation of Ferrous Sulphate oral solution. (Each 5 mL contains Ferrous Sulphate BP 200 mg) 06 – 10

03. Formulation and preparation of Chlorpheniramine oral solution. (Each 5 mL contains Chlorpheniramine Maleate BP 2 mg) 11 – 15

04. Formulation and preparation of Antacid Suspension.

(Each 5 mL contains Aluminum Hydroxide 200 mg and Magnesium Hydroxide 400 mg) 16 – 20

05. Formulation and preparation of Metronidazole oral Suspension.

(Each 5 mL contains Benzoyl Metronidazole BP 320 equivalent to Metronidazole BP 200 mg) 21 – 26

06. Formulation and preparation of Preparation of oil in water (O/W)

emulsion. (Each 5 mL contains 0.5 mL castor oil) 27 – 31

Bibliography. 31

= Table Of Contents

Md. Imran Nur Manik

Pharmaceutical Technology-I Lab

Prepared By: Md. Imran Nur Manik Page 1

Lecturer; Department of Pharmacy; Northern University Bangladesh (NUB . )

Experiment No. 01

Name of the Experiment: Formulation and preparation of pediatric paracetamol oral solution. (Each 5 mL contains Paracetamol BP 120 mg)

Introduction

In pharmaceutical terms, solutions are “liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents”. Generally solution is a homogeneous mixture, prepared by dissolving a solid, liquid, or gas in another liquid, in which the solute molecules or dissolved substance are dispersed among those of the solvent. Based on use, the pharmaceutical solution’s may be classified as oral, otic, ophthalmic, or topical. For example, aqueous solutions containing a sugar are classified as syrups; sweetened hydro-alcoholic (combinations of water and ethanol) solutions are termed elixirs etc. Oral solutions such as syrups, elixirs, spirits, and tinctures are prepared & used for the specific effects of the medicinal agents they carry. Solutes other than the medicinal agent are usually present in orally administered solutions. These additional agents are frequently included to provide colour, flavour, sweetness, or stability. In formulating or compounding a pharmaceutical solution, the solubility and stability of each solute with regard to the solvent or solvent system must be considered. Advantages and disadvantages of pharmaceutical solutions for oral administration Advantages

Therapeutic agents can easily be administered orally to individuals who have difficulty in swallowing, e.g. elderly patients, infants.

The therapeutic agent is dissolved in the formulation and is therefore immediately available for absorption.

The bioavailability of pharmaceutical solutions is greater than that of oral solid-dosage forms. Taste-masking of bitter therapeutic agents can be readily achieved.

Disadvantages Pharmaceutical solutions for oral administration are unsuitable for therapeutic agents that are chemically unstable in the presence of water. The poor solubility of certain therapeutic agents may prohibit their formulation as pharmaceutical solutions. Pharmaceutical solutions are expensive to ship and are bulky for the patient to carry due to the associated mass of the product.

Syrups are sweet, viscous, concentrated aqueous preparations of sugar or sugar Syrups: substitute with or without flavours and medicinal substances. The concentration of sugar in syrup should be 66.7% (w/w) according to BP. (85%w/v in USP) Types of Syrups: Non-medicated syrup: Syrups containing various aromatic or pleasantly flavored substances and are intended to be used as a vehicle or flavor for prescriptions are called non medicated or flavoured syrups. For example Acacia, Cherry, Cocoa, Orange, and Raspberry USP. Medicated syrup: Syrups containing a therapeutic agent are called medicated syrups. Medicated syrup is formulated by the components; API along with the sucrose, purified water, flavouring agent & other excipients.

Md. Imran Nur Manik




Components of Syrup: Most syrups contain the following components in addition to the purified water or Distilled Water (DW) and any medicinal agents present. The sugar, usually Sucrose or Sucrose substitutes: Which provides sweetness and viscosity. Antimicrobial preservatives. Flavorants. Colorants. Commercial syrups contain special solvents, solubilizing agents, thickeners or stabilizers. Advantages of Syrup: Syrups have the following advantages; i. Syrups can retard oxidation by partly hydrolysing into reducing sugar such as laevulose and dextrose. ii. It prevents decomposition of many vegetable substances; syrups have high osmotic pressure which prevents microbial growth. iii. They are palatable due to the presence of sugar, thus provides suitable vehicle for the administration of bitter and bad odorous substances. iv. They are more quickly effective than solid dosages forms like tablet, capsule etc. v. They are homogenous formulation so the active ingredients are also homogenously distributed. vi. Syrups are suitable formulation for the paediatric and geriatric patients. Disadvantages of Syrup: Some disadvantages of Syrups are as follows; i. In a closed container of syrup, surface dilution is possible due to solvent evaporation. ii. Solvent evaporation condenses in the upper internal surface of the container and then flows back on to the surface of the product which provides an ideal medium for the growth of certain microorganisms. iii. During storage and use of syrup, crystallization of the sugar within the screw cap may occur. This problem is solved by the addition of polyhydric alcohols. Preparation of 66.7% Sucrose syrup BP Take 66.7 gram sucrose B.P. Add purified water B.P with continuous trituration to mix the sugar. Heat together until dissolved and add sufficient boiling Purified Water to produce 100 g. Paediatric Paracetamol Oral Solution is a solution containing 2.4% w/v of Paracetamol in a suitable flavoured vehicle.

Formula:[60 mL]

A non-sugar based product can be prepared by omitting Syrup and adding non-sugar sweeting agents (e.g. Saccharine, Aspartame, Sucralose) for diabetes patients.

Name of the ingredients Theoretical amount Purpose Paracetamol BP 1.44 gm API. Analgesic, Antipyretic. Propylene glycol BP 5 mL Co-solvent, Preservative. Sucrose Syrup (66.7%)BP 20 mL Increase viscosity, Sweeting agent.

Sorbitol Solution (70%) BP 10 mL Sweeting agent, Retard crystallization of sucrose around the cap of the bottles. Stabilizing agent.

Glycerin BP 5 mL Increase viscosity, Sweeting agent. Solvent. Increase the solubility of added ingredients.

Methyl 4-Hydroxybenzoate BP 50 mg / 0.05 gm Antimicrobial preservative. Propyl 4-Hydroxybenzoate BP 5 mg / 0.005 gm Antimicrobial preservative. Flavor Q.S.

Improving organoleptic Property. Color Q.S. Purified water Q.S. up to 60 mL Solvent/Vehicle.

Md. Imran Nur Manik




Apparatus: 1. Beaker 2. Stirrer/Glass rod 3. Electric balance 4. Measuring cylinder 5. Bottle Calculation: 60 mL syrup contain =1.44 gm or 1440 mg of paracetamol

Thus , 1 mL ” ” 60

1440 mg of ’’

So, 5 mL ” ” 60

51440 mg of ’’

= 120 mg of paracetamol Recipe: For 60 mL paracetamol syrup where each 5 mL contains 120 mg of paracetamol BP Since 5 mL contains 120 mg, thus 60 mL would contain 1440 mg or 1.44 gm paracetamol BP Method of preparation: 1. Take 1.44 gm Paracetamol in a beaker. 2. Dissolve it by adding 5 mL propylene glycol. 3. Subsequently add 20 mL sucrose syrup & 5 mL glycerin. Mix them properly. 4. Afterwards add 10 mL sorbitol solution. 5. Now add the preservatives; namely 50 mg Methyl Hydroxybenzoate, 5 mg Propyl Hydroxybenzoate (Better to dissolve in propylene glycol/Glycerin, with some DW). 6. After complete mixing of all the portions, add the flavor& color (e.g. Orange/Raspberry) 7. Later transfer the syrup to a measuring cylinder adjusts the volume to 60 mL by adding purified water. 8. Finally transfer the preparation into a bottle, close properly & label it. Function of each ingredient: 1. Paracetamol:( para-acetyl-amino-phenol ,N-acetyl-para-aminophenol) Acetaminophen is an odorless, slightly bitter taste white or almost white, crystalline powder. It is freely soluble in alcohol; soluble in methanol but very slightly soluble in cold water, soluble in boiling water. Propylene glycol may be used for good solubility. It is the active ingredient of the preparation acting as antipyretic & analgesic. 2. Propylene Glycol Propylene glycol is a useful solvent with a wide range of applications and is frequently substituted for glycerin in modern pharmaceutical formulations. Properties: i. Clear, colorless, practically odorless iii. Viscous ii. Hygroscopic in nature iv. Usually tasteless (/faintly sweet) Functions: ♦ Solvent or co-solvent (Oral , Parenterals, Topical, Aerosol) ♦ Disinfectant ♦ Antimicrobial preservative (Solutions, Semisolids) ♦ Humectant (Topical)

Md. Imran Nur Manik




3. Sucrose syrup It is used in the preparation as sweetening agent to mask the bitter taste of preparation. Sucrose: (β-D-Fructofuranosyl α-D-glucopyranoside.) Properties: ♦ Colorless or Brown, Odorless, Crystalline Powder. ♦ Viscous in nature. ♦ It has a sweet taste. ♦ Free flowing (crystalline sucrose). ♦ Cohesive solid (Powder Sucrose). Sucrose:C12H22O11 ♦ Melting Point: 160°C –186°C (with decomposition) ♦ Good stability at room temperature and at moderate relative humidity. ♦ Dilute sucrose solutions are liable to fermentation by microorganisms. ♦ Sucrose is also considered to be more cariogenic than other carbohydrates since it is more easily converted to dental plaque. For this reason, its use in oral pharmaceutical formulations is declining. Functions: ♦ Sweetening Agent: Used to enhance palatability. ♦ Viscosity imparting agent: Used to increase viscosity. 4. Sorbitol Solution Sorbitol is D-glucitol. It is a hexahydric alcohol related to mannose and is isomeric with mannitol. Sorbitol: Sorbitol is widely used as an excipient in pharmaceutical formulations. Properties: i. Odorless, white or almost colorless iii. Crystalline ii. Hygroscopic powder iv. Sweet in taste Functions: ♦ Prevent crystallization of sugar around the cap of bottles ♦ Sweetener ♦ Vehicle in sugar-free formulations (♦ Stabilizing agent) ♦ Humectant 5. Glycerin:( Glycerol; Glycerine) Glycerin is used in a wide variety of pharmaceutical formulations including oral, otic, ophthalmic, topical, and parenteral preparations. Glycerin has preservative qualities and is often used as a stabilizer and as an auxiliary solvent in conjunction with water or alcohol. Properties: i. Clear, colorless, odorless iii. Viscous ii. Hygroscopic liquid iv. Sweet in taste (App. 0.6 times as sweet as sucrose) Functions: ♦ Solvent, Co-solvent ♦ Humectant ♦ Antimicrobial preservative ♦ Viscosity increasing agent ♦ Sweetening agent 6. Methyl & Propylparaben: (parabens : Alkyl esters of p-hydroxybenzoic acid ) Methylparaben is widely used as an antimicrobial preservative in cosmetics, food products, and pharmaceutical formulations.

Methylparaben Properties:

i. Colorless crystals or a white crystalline powder ii. Odorless or almost odorless .Slight burning taste.

Md. Imran Nur Manik




Propylparaben Properties: i. White iii. Odorless ii. Crystalline powder iv. Tasteless Function: i. Methylparaben & Propylparaben (10:1) exhibit antimicrobial activity over the pH range 4–8. ii. They are also more active against Gram-positive than against Gram-negative bacteria. Activity may be improved by using combinations of parabens, as synergistic effects occur.

Other ingredients that can be used: √ Vehicle: Macrogols (PEG) (Dissolution enhancer, Solubilizing agent) √ Sweetening agent(Other than sugar): Sorbitol, Glycerol and Propylene glycol. √ Preservatives: Na-benzoate, Benzoic acid and salts, Sorbic acid and its salts. √ Coloring agent: Amaranth, Apple green. √ Flavoring agent: Peppermint oil, clove oil, vanilla, lemon oil etc. √ Buffer: Na-citrate, potassium bisulfite. Indications: Paediatric paracetamol oral solution is indicated to be used-

As antipyretic & analgesic agent. ( temporarily relieve fever) In mild to moderate pain myalgia, headache, toothache, arthritis and backache. Contraindications: Severe hepatic impairment & renal impairment; Allergy

Dose: The dose of syrup is as follows Children under 3 months: 10 mg/kg body weight (reduce to 5 mg/ kg if jaundiced 3–4 times/day Children (below 1yr) : ½ -1 teaspoonful syrup 3–4 times/day Children (6-12yrs) : 2–4 teaspoonful syrup 3–4 times/day Or, as per the recommendation of the physician.( Maximum 4 doses in 24 hours.)

Paracetamol BP Oral solution

Palatable 60 mL Solution, Sugar Free Each 5 mL Contains Paracetamol BP 120mg

Batch No. : 0171740

Mfg. Date : Apr 2018

Exp. Date : Mar 2020

M.R.P. Tk. : 23 (Including all taxes.)

Mfg. Lic. No. : 12 & 80

DAR No. : 025-0144-088

Indication : Antipyretic , Analgesic, Fever,

Common cold, Influenza, Headache.

Dose : As Directed By The Physician

Storage condition:

Should be protected from light.

Should not be refrigerated.

Precaution: Keep every medicine out of reach of children. Manufactured by: Northern Laboratories Ltd. 24, Mirpur road, Dhaka-1215, Bangladesh.

Market preparation: Paediatric paracetamol oral solution. SL. Trade/Brand Name Manufacturer Dosage form 01 02 03 04 05

Md. Imran Nur Manik




Experiment No. 02

Name of the Experiment: Formulation and preparation of Ferrous Sulphate oral solution. (Each 5 mL contains Ferrous Sulphate BP 200 mg)

Introduction: Pharmaceutical syrup is concentrated, aqueous preparation of sugar or sugar substitute with or without added flavoring agents and medicinal substances. Ferrous Sulphate oral solution belongs to a group of medicines called iron supplements. These medicines work by replacing body iron. Iron is a key component which is required for the production of red blood cells (a process known as haematopoiesis), but it's also part of haemoglobin (that is the pigment of the red blood cells) binding to the oxygen and thus facilitating its transport from the lungs via the arteries to all cells throughout the body.. When the body does not get enough iron, it cannot produce the number of normal red blood cells needed to keep good health. This condition is called iron-deficiency anaemia. Ferrous sulphate is an iron salt which contains elemental iron or ferrous iron and used for the prevention and treatment of iron deficiency anemia before, during and after pregnancy as well as during lactation. Anemia Anemia is a decrease in the total amount of red blood cells (RBCs) or hemoglobin in the blood, or a lowered ability of the blood to carry oxygen. The oxygen carrying capacity is determined by hemoglobin content of the erythrocytes. Hence a reduction in the blood hemoglobin level & the number of circulating erythrocytes is the characterization of anemia.

Classification According to the etiology, anaemia may be classified as follows: Anaemia due to blood loss by hemorrhage.

Anaemia due to dietary deficiency of factors essential for normal blood production.

e.g. Iron, Folic Acid. Anaemia due to excessive blood cell destruction in comparison to the production .

Anaemia due to aplasia (Failure of an organ or tissue to develop normally),

hypoplasia Underdevelopment of a tissue organ or body), or destruction of bone marrow. Anaemia due to infection, rheumatic arthritis etc.

Anaemia due to defective formation of R.B.C.

Iron deficiency anemia is caused by the deficient synthesis of hemoglobin in which iron is an important constituent. Males of average height have about 4 grams of iron in their body; females about 3.5 grams and children will usually have 3 grams or less. These 3-4 grams are distributed throughout the body in haemoglobin, tissues, muscles, bone marrow, blood proteins, enzymes, ferritin, hemosiderin, and transport in plasma.

Apparatus: 1. Beaker 2. Stirrer 3. Measuring cylinder 4. Pipette 5. Bottle 6. Funnel 7. Glass rod 8. Mortar and pestle 9. Electric balance.

Md. Imran Nur Manik




Recipe: For 60 mL Iron Syrup

Each 5 mL contains 200 mg of FeSO4 Then 60 mL contains

5

60200 mg of FeSO4

=2400 mg of FeSO4 =2.4 gm of FeSO4

Formula: For 60 mL Iron syrup

Each 5 mL contains 200 mg of FeSO4

Method of preparation:

1. Take 2.4 gm ferrous sulphate in a mortar & crush it properly with pestle. 2. Now take 10 mL DW in a 250 mL beaker. Add ascorbic acid and citric acid into it, mix them properly. 3. Afterwards add the ferrous sulphate (previously crushed in step 1) and dissolve in this beaker. Later add 20 mL sucrose syrup to it. 4. Take 5 mL DW in a 50 mL beaker and add 0.05 gm Methyl Hydroxybenzoate, 0.005 gm Propyl Hydroxybenzoate and dissolve in it (Better to dissolve in Propylene glycol/Glycerin. Add some DW & then add to the syrup). Later add 5 mL Sorbitol & 5 mL Glycerin to it and blend them properly. 5. Add this new solution (made in the step 4) to the 250 mL beaker containing ferrous sulphate solution (obtained in step 3). Blend them appropriately to get a uniform mixture. 6. After homogenous mixing of all the portions, add the flavor & color. 7. Now transfer the syrup in a measuring cylinder, adjust the volume to 60 mL by adding purified water Q.S. 8. Finally transfer the preparation in a bottle, close the bottle properly & label it.

Name of the ingredient Theoretical weight Purpose

Ferrous Sulphate BP 2.4 gm API. For the treatment of iron deficiency anemia and anemia due to pregnancy.

Citric acid BP 200 mg / 0.2 gm Buffering agent; Acidifying agent. Ascorbic acid BP 100 mg / 0.1 gm Antioxidant.

Sorbitol Solution (70%) BP 5 mL Retard crystallization of sucrose; Sweetener, Humectant.

Sucrose Syrup BP 20 mL Viscosity imparting &sweetening agent. Methyl 4-Hydroxybenzoate BP 50 mg/ 0.05 gm Antimicrobial preservative. Propyl 4-Hydroxybenzoate BP 5 mg/ 0.005 gm Antimicrobial preservative. Glycerin BP 5 mL Viscosity imparting agent; Humectant. Flavor Pharma Grade Q.S.

Improve organoleptic property. Color FDC Q.S. Purified Water BP Q.S. to 60 mL Solvent/ Vehicle.

Md. Imran Nur Manik




Function of the ingredients:

1. Ferrous Sulphate (FeSO4.7H2O):

It is the active ingredient of the hematinic preparation. Ferrous Sulfate is used for the prevention and treatment of iron-deficiency anaemia.

Properties: √ Physical form : Crystal or crystalline powder, Efflorescent in air. √ Color : Light green, Bluish-green (Oxidized to brown in moist air). √ Odor : Odorless. √ Taste : Metallic in taste. √ Nature : Acidic in nature. √ pH : Is about 3.7. (3.0 ― 4.0) √ Solubility : Freely soluble in water, very soluble in boiling water.

2. Citric acid :( Citric acid monohydrate) 2-Hydroxypropane-1,2,3-tricarboxylic acid monohydrate. Properties: i . Colorless or translucent crystals or granules, /or as a white crystalline powder. ii. Odorless. iii. Strong acidic taste. iv. Efflorescent. v. It is slightly deliquescent in moist air. vi. Melting point 100°C (Monohydrate), 153°C (anhydrous).

Functions: ♦ Buffering agent (adjust the pH of solutions) ♦ Sequestering agent ♦ Acidifying agent ♦ Sialogogue An agent increasing the flow of saliva. ♦ Flavor enhancer ♦ Antioxidant synergist. 3. Ascorbic acid: Properties: √ Physical form : White or almost white, crystalline powder or colorless crystals. √ Color : Light Yellow. Gradually darkens in color upon exposure to light. √ Odor : Odorless. √ Taste : Sharp, acidic taste. √ Nature : Non-hygroscopic. √ PH : Between 2.1–2.6 √ Melting point : 190°C (with decomposition). Functions: Antioxidant (0.01-0.1% w/v). Stabilizing agent. pH adjusting agent (for injection). Adjunct for oral liquids

4. Sorbitol Solution Sorbitol is D-glucitol. It is a hexahydric alcohol related to mannose and is isomeric with mannitol. Sorbitol (D-Glucitol): Sorbitol is widely used as an excipient in pharmaceutical formulations.

Md. Imran Nur Manik




Properties: i. Odorless, white or almost colorless iii. Crystalline ii. Hygroscopic powder iv. Sweet in taste Functions: Prevent crystallization of sugar around the cap of bottles Sweetener

Vehicle in sugar-free formulations Stabilizing agent Humectant

5. Sucrose syrup It is used in the preparation as sweetening agent to mask the bitter taste of preparation. Sucrose: (β-D-Fructofuranosyl α-D-glucopyranoside.)

Properties: Colorless or Brown, Odorless, Crystalline Powder. Viscous in nature. It has a sweet taste. Free flowing (crystalline sucrose). Cohesive solid (Powder Sucrose). Melting Point: 160°C –186°C (with decomposition) Good stability at room temperature and at moderate relative humidity. Sucrose:C12H22O11 Dilute sucrose solutions are liable to fermentation by microorganisms. Sucrose is also considered to be more cariogenic than other carbohydrates since it is more easily converted to dental plaque. For this reason, its use in oral pharmaceutical formulations is declining. Functions: ♦ Sweetening Agent: Used to enhance palatability. ♦ Viscosity imparting agent: Used to increase viscosity. 6. Methyl & Propylparaben: (Parabens : Alkyl esters of

p-hydroxybenzoic acid ) Methylparaben is widely used as an antimicrobial preservative in cosmetics, food products, and pharmaceutical formulations.


i. Colorless crystals or a white crystalline powder ii. Odorless or almost odorless .Slight burning taste.

Propylparaben Properties: i. White iii. Odorless ii. Crystalline powder iv. Tasteless Function: i. Methylparaben & Propylparaben exhibit antimicrobial activity over the pH range 4–8. ii. They are also more active against Gram-positive than against Gram-negative bacteria. Activity may be improved by using combinations of parabens, as synergistic effects occur.

7. Glycerin:( Glycerol; Glycerine) Glycerin is used in a wide variety of pharmaceutical formulations including oral, otic, ophthalmic, topical, and parenteral preparations. Glycerin has preservative qualities and is often used as a stabilizer and as an auxiliary solvent in conjunction with water or alcohol.

Md. Imran Nur Manik




Properties: i. Clear, colorless, odorless iii. Viscous ii. Hygroscopic liquid iv. Sweet in taste (App. 0.6 times as sweet as sucrose) Functions: ♦ Solvent, Co-solvent ♦ Humectant ♦ Sweetening agent ♦ Antimicrobial preservative ♦ Viscosity increasing agent Other ingredients used: √ Coloring agent: Amaranth, Apple green. FD&C yellow No. 6 (sunset yellow FCF) √ Flavoring agent: Raspberry/Orange flavor. Guarana flavor 12144–33 Indications: Iron preparations are used in - Iron deficiency anemia. Pregnancy and lactation induced iron deficiency. Dosage and Administration:

Adult: Initial therapeutic dose: 3–4½ teaspoonful daily in divided doses or as prescribed by the physician.

Maintenance dose: 1½ teaspoonful daily, but if needed up to 1.8 gm (9 teaspoonful) daily can be given.

Children : Under 1 year : ¼ teaspoonful thrice daily or as directed by physician. 1-5 years : 1 teaspoonful thrice daily. 6-12 years : 1½ teaspoonful twice daily. Contraindications: Iron therapy is contraindicated in hemachromatosis and hemosiderosis. Side effects: Some general & common side effects are as follows:- General:

1. Constipation. 2. Black discoloration of faeces. 3. Temporary staining of teeth. 4. Nausea, Vomiting, Diarrhoea.

Severe: Gastro-intestinal erosion (with high doses). Blood in stool.

Ferrous Sulphate Syrup BP

Each 5 mL contains Ferrous Sulphate Heptahydrtate BP 200mg

Batch No. : 0171740

Mfg. Date : Oct 2017

Exp Date : Oct 2019

M.R.P. Tk. : 67 (Including VAT)

Indications : Iron deficiency syndrome and Anaemia.

Dose : To be written from- Dosage and Administration

Storage condition: Keep in cool and dry place.

Precaution : Keep every medicine out of reach of children.

DAR No. : 025-0144-088

Mfg. Lic. No. :12 & 80 Manufactured by: Northern Laboratories Ltd. 24, Mirpur road, Dhaka-1215, Bangladesh.

Market preparation: Ferrous Sulphate Syrup BP SL. Trade/Brand Name Manufacturer Dosage form 01 02 03 04 05

Md. Imran Nur Manik




Experiment No. 03

Name of the Experiment: Formulation and preparation of Chlorpheniramine oral solution. (Each 5 mL contains Chlorpheniramine Maleate BP 2 mg)

Introduction: Syrup is a viscous concentrated solution of a sugar, such as sucrose, in water or other aqueous liquid; combined with other ingredients.

Chlorpheniramine maleate is an antihistamine which reduces allergic vasodilatation and mucosal congestion. It is a first-generation alkyl amine antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. It works by blocking the action of histamine, which helps reduce symptoms such as watery eyes and sneezing. Its sedative effects are relatively weak compared to other first-generation antihistamines. Although not generally approved as an antidepressant or anti-anxiety medication, chlorphenamine appears to have these properties as well.

Apparatus: 1. Beaker 3. Measuring cylinder 5. Electric balance 7. Glass rod 2. Funnel 4. Pipette 6. Bottle Recipe: For 60 mL Chlorphenamine maleate Syrup:

Each 5 mL contains 2 mg Chlorphenamine maleate

For 60 mL syrup it requires 5

602 mg of Chlorphenamine maleate

= 24 mg of Chlorphenamine maleate = 0.024 gm of Chlorphenamine maleate

Formula: For 60 mL Chlorpheniramine Maleate solution Each 5 mL contains 2 mg Chlorphenamine maleate

Name of Ingredient Theoretical weight Purpose Chlorpheniramine Maleate BP 24 mg / 0.024 gm API. (H1 histamine receptor antagonist). Sucrose Syrup BP 20 mL Viscosity imparting &Sweetening agent.

Glycerin BP 5 mL Retard crystallization of sucrose; Sweetener, Humectant.

Sorbitol Solution (70%) BP 6 mL Viscosity imparting agent; Humectant, Sweetener; Anti-crystallization Agent

Methyl 4-Hydroxybenzoate BP 80 mg / 0.08 gm Antimicrobial Preservative. Propyl 4-Hydroxybenzoate BP 8 mg / 0.008 gm Antimicrobial Preservative. Citric Acid BP 80 mg / 0.08 gm Antioxidant; Buffer; Acidifying agent. Sodium Citrate BP 60 mg / 0.06 gm Alkalizing agent; Buffering agent. Flavor Q.S.

Improve organoleptic property. Color Q.S. Distilled water Q.S. up to 60 mL Solvent / Vehicle.

Md. Imran Nur Manik





1. At first take 0.024 gm Chlorpheniramine maleate in a 250 mL beaker and dissolve it in 10 mL DW.

2. Afterwards add 20 mL sugar syrup, 6 mL sorbitol solution, 5 mL glycerol, 0.06 gm Na- citrate, 0.08 gm citric acid, 0.08 gm Methylparaben, 0.008 gm Propylparaben step by step in the Chlorpheniramine maleate solution. Carefully mix all the ingredients with proper stirring.

3. After uniform blending of all the portions, add the organic flavor and color and mix them

appropriately.

4. Later transfer the whole content of the beaker in a 100 mL measuring cylinder and adjust the volume to 60 mL by the addition of purified water.

5. Finally transfer the preparation in a bottle. Close & label the bottle properly.

Functions of each ingredient:

1. Chlorpheniramine Maleate: It is the active ingredient of the preparation. It acts as Histamine H1 receptor antagonist; commonly known as antihistamines.

Properties: √ Physical form : Crystalline powder. √ Color : White. √ Odor : Odorless. √ Solubility : Soluble in 4 parts of water, 10% ethanol (96%) 10 parts of chloroform, slightly soluble in ether.

2. Sucrose syrup: It is used in the preparation as sweetening agent to mask the bitter taste of preparation. Sucrose: (β-D-Fructofuranosyl α-D-glucopyranoside.)

Properties: Colorless or Brown, Odorless, Crystalline Powder. Viscous in nature. It has a sweet taste. Free flowing (crystalline sucrose). Cohesive solid (Powder Sucrose). Melting Point: 160°C –186°C (with decomposition) Good stability at room temperature and at moderate relative humidity. Sucrose:C12H22O11 Dilute sucrose solutions are liable to fermentation by microorganisms. Sucrose is also considered to be more cariogenic than other carbohydrates since it is more easily converted to dental plaque. For this reason, its use in oral pharmaceutical formulations is declining. Functions: ♦ Sweetening Agent: Used to enhance palatability. ♦ Viscosity imparting agent: Used to increase viscosity.

Md. Imran Nur Manik




3. Glycerin:( Glycerol; Glycerine) Glycerin is used in a wide variety of pharmaceutical formulations including oral, otic, ophthalmic, topical, and parenteral preparations. Glycerin has preservative qualities and is often used as a stabilizer and as an auxiliary solvent in conjunction with water or alcohol. Properties: i. Clear, colorless, odorless iii. Viscous ii. Hygroscopic liquid iv. Sweet in taste (App. 0.6 times as sweet as sucrose) Functions: ♦ Solvent ♦ Co-solvent ♦ Humectant ♦ Sweetening agent ♦ Antimicrobial preservative ♦ Viscosity increasing agent 4. Sorbitol Solution Sorbitol is D-glucitol. It is a hexahydric alcohol related to mannose and is isomeric with mannitol. Sorbitol (D-Glucitol): Sorbitol is widely used as an excipient in pharmaceutical formulations. Properties: i. Odorless, white or almost colorless iii. Crystalline ii. Hygroscopic powder iv. Sweet in taste Functions: Prevent crystallization of sugar around the cap of bottles

Sweetener Vehicle in sugar-free formulations

Stabilizing agent Humectant

5. Methyl & Propylparaben: (Parabens : Alkyl esters of p-hydroxybenzoic acid ) Methylparaben is widely used as an antimicrobial preservative in cosmetics, food products, and pharmaceutical formulations. Methylparaben Properties:

i. Colorless crystals or a white crystalline powder ii. Odorless or almost odorless. iii. Slight burning taste.

Propylparaben Properties: i. White iii. Odorless ii. Crystalline powder iv. Tasteless Function: i. Methylparaben & Propylparaben exhibit antimicrobial activity over the pH range 4–8. ii. They are also more active against Gram-positive than against Gram-negative bacteria. Activity may be improved by using combinations of parabens, as synergistic effects occur.

Md. Imran Nur Manik




6. Citric acid :( Citric acid monohydrate) 2-Hydroxypropane-1,2,3-tricarboxylic acid monohydrate. Properties: i. Colorless or translucent crystals or granules, /or as a white crystalline powder. ii. Odorless. iii. Strong acidic taste. iv. Efflorescent. v. It is slightly deliquescent in moist air. vi. Melting point 100°C (Monohydrate), 153°C (anhydrous).

Functions: ♦ Buffering agent (adjust the pH of solutions) ♦ Sequestering agent ♦ Acidifying agent ♦ Sialogogue An agent increasing the flow of saliva. ♦ Flavor enhancer ♦ Antioxidant synergist.

7. Sodium Citrate (dihydrate) Trisodium citrate; C6H5Na3O7.2H2O

Properties: i. Monoclinic crystals or a white crystalline powder. ii. Odorless, colorless. iii. Cooling, saline (sour) taste. iv. It is slightly deliquescent in moist air and efflorescent in warm dry air. Functions: ♦ Buffering agent ♦ Sequestering agent ♦ Preservatives and Antioxidants ♦ Alkalizing agent ♦ Emulsifying agent ♦ Processing Aids and Additives Other ingredients used: Organic flavour : It is used as flavouring agent. Green banana flavour Organic colour : It is used as colouring agent. Distilled water : Used as vehicle. Indications: Chlorpheniramine relieves- Urticarial rashes, Red, itchy, watery eyes; Pruritus, Sneezing; insect bites and stings Itchy nose or throat; and Runny nose caused by allergies, hay fever, and the common cold.

Side-effects

♦ Drowsiness ♦ Headache, ♦ Psychomotor impairment, ♦ Urinary retention ♦ Dry mouth, ♦ Blurred vision, ♦ Gastro-intestinal disturbances. ♦ Hypotension, ♦ Palpitation, ♦ Arrhythmias, ♦ Extrapyramidal effects, ♦ Dizziness, ♦ Confusion, ♦ Depression, ♦ Sleep disturbances, ♦ Tremor, ♦ Convulsions, ♦ Blood disorders, ♦ Liver dysfunction ♦ Angle-closure glaucoma and ♦ Hypersensitivity reactions (including bronchospasm,

angioedema, and anaphylaxis, rashes, and photosensitivity reactions).

Md. Imran Nur Manik




Cautions and contra-indications Must be used with caution in-

Prostatic hypertrophy, Urinary retention, Angle-closure glaucoma Pyloroduodenal obstruction Hepatic disease Eepilepsy.

Dose:

Adults and children 12 years and over: 10 mL (4 mg) every 4 to 6 hourly. Maximum daily dose: 60 mL (24 mg) in any 24 hours.

Children

6 - 12 years: 5 mL (2 mg) every 4 to 6 hourly. Maximum daily dose: 30 mL (12 mg) in any 24 hours.

2 - 6 years: 2.5 mL (1mg) every 4 to 6 hourly. Maximum daily dose: 15 mL (6 mg) in any 24 hours.

1 - 2 years: 2.5 mL (1 mg) twice daily. The minimum interval between the doses should be 4 hours. Maximum daily dose: 5 mL (2 mg) in any 24 hours.

Not recommended for children below 1 year

Chlorpheniramine Syrup

Each 5 mL contains Chlorpheniramine Maleate BP 2 mg Batch No. : 0171740


Exp Date : Oct 2019

M.R.P. Tk. : 67

Mfg. Lic. No. :12 & 80

Indication: Allergic conditions such as rhinitis and urticaria. Dose: As directed by Physician Storage condition: Keep in cool and dry place Precaution:

Keep every medicine out of reach of children. Oral administration only DAR No. : 025-0144-088

Manufactured by: Northern Laboratories Ltd. 24, Mirpur road, Dhaka-1215, Bangladesh.

Market preparation: Chlorpheniramine Maleate Syrup SL. Trade/Brand Name Manufacturer Dosage form 01 02 03 04 05

Md. Imran Nur Manik




Experiment No. 04 Name of the Experiment: Formulation and preparation of Antacid Suspension. (Each 5 mL contains Aluminum Hydroxide 200 mg and Magnesium Hydroxide 400 mg)

Introduction: Suspensions may be defined as a coarse dispersion in which finely divided insoluble drug particles (the suspensoid) generally greater than 1µm in diameter are dispersed uniformly throughout a liquid medium in which the drug exhibits a minimum degree of solubility. A coarse suspension is a dispersion of finely divided, insoluble solid particles (the disperse phase) in a fluid (the dispersion medium or continuous phase). Most pharmaceutical suspensions consist of an aqueous dispersion medium, although in some instances it may be an organic or oily liquid. A gastric antacid is a chemical substance introduced into the stomach for the purpose of lowering the hydrogen ion concentration, or acidity, of the gastric contents; resulting in an increase in the pH of stomach and duodenum. Gastric acidity occurs due to excessive secretion of HCl in stomach due to various reasons. The suspension form of antacids is given for faster absorption, because the rate of dissolution is higher than tablets. It is because of resulting from higher surface area provided by smaller fine particles. Such antacids are in common use in medical practice, mostly in the treatment of peptic ulcer. They react with gastric HCl and neutralize the acids as follows:

Al (OH) 3+3HClAlCl3+3H2O

Mg(OH)2+2HCl→MgCl2+2H2O

Classification: a. Systemic Antacid:

Systemic antacids are antacids which get systemically absorbed. They are capable of producing metabolic alkalosis because the certain moiety does not form insoluble basic compound in the intestine e.g. NaHCO3, KHCO3, Na-citrate etc.

b. Non Systemic Antacid:

A non- insoluble basic systemic antacid is one which forms insoluble basic compound in the intestine and is not subsequently absorbed. So these antacids do not produce systemic alkalosis. e.g. Al(OH)3,Ca(OH)2 Mg(OH)2, Ca3(PO4)2,Mg-trisilicate.

Apparatus: 1. Beaker 3.Stirrer 5. Measuring cylinder 7. Droppers

2. Mortar 4.Pestle 6. Funnel 8. Electric balance Recipe: Note: Actual 5 mL formulation contains dried Al (OH) 3 Gel USP equivalent to 200 mg Al2O3,

400mg Mg(OH)2 BP and 30 mg Simethicone USP (which is omitted here).

For 60 mL Antacid Suspension (Calculation is only for Al(OH)3): Each 5 mL contains 200 mg Al(OH)3

Then 60 mL contains 5

60200 mg of Al(OH)3

=2400 mg of Al(OH)3 =2.4 gm of Al(OH)3

Md. Imran Nur Manik




Formula: Each 5 mL suspension contains 200 mg of Al(OH)3 & 400 mg of Mg(OH)2

Method of Preparation: 1. Take 2.4 gm Al (OH) 3 & 4.8 gm Mg(OH)2 in a mortar. Crush them properly and then dissolve them in 10 mL DW with continuous trituration by pestle in order to get a uniform mixture. 2. Then take 0.4 gm Na-CMC along with 10 mL DW in a 50 mL beaker. Mix it slowly to make uniform mucilage. 3. Now mix the Al(OH)3 & Mg(OH)2 solution (previously made in the step one) and Na-CMC mucilage (from the step two) in a 250 mL beaker. Appropriately blend these two solutions to get a homogenous mixture. 4. Afterwards add 10 mL Sorbitol solution, 3 mL Glycerine, 0.1 gm Methyl Hydroxybenzoate, 0.01 gm Propyl Hydroxybenzoate, 0.015 gm Saccharine sodium and 0.05 gm Na-Citrate. Mix them thoroughly with continuous stirring. 5. Finally add organic oil (Flavor) with triturate to mix it with the preparation properly. 6. Take the final solution in a measuring cylinder and adjust the volume to 60 mL by adding sufficient quantity of purified water. 7. From the cylinder, transfer the final preparation in a well-polished bottle. Finally cork & label the bottle. Function of ingredients:

1. Al(OH)3 and Mg(OH)2: Al(OH)3 and Mg(OH)2 are the active part of the preparation. They act as antacid and serve to reduce acidity.

Name of the ingredient Weight Purpose/Justification Dried Aluminium Hydroxide 2.4 gm API. Gastric antacid. Magnesium hydroxide 4.8 gm API. Gastric antacid. Na-CMC BP 0.4 gm Suspending agent

Glycerin BP 3 mL Retard crystallization of sucrose; Sweetener, Humectant.

Sorbitol Solution (70%) BP 10 mL Viscosity imparting agent; Humectant, Sweetener; Anti-crystallization Agent

Methyl 4-Hydroxybenzoate BP 100 mg / 0.1 gm Antimicrobial Preservative. Propyl 4-Hydroxybenzoate BP 10 mg / 0.01 gm Antimicrobial Preservative. Saccharine Sodium BP 15 mg / 0.015 gm Sweetening agent. 500 × more sweet than sucrose

Sodium Citrate BP 50 mg / 0.05 gm Flocculating agent. Flavour Q.S.

Improving organoleptic properties. Colour Q.S Purified Water BP Q.S. to 60 mL Solvent/Vehicle.

Md. Imran Nur Manik




Properties: Al(OH)3

√ Physical form : Amorphous powder √ Color : White √ Odor : Odorless √ Solubility : Soluble in dilute mineral acids and aqueous solutions of Alkali hydroxides. Insoluble in water.

Properties: Mg (OH)2 √ Physical form : Fine amorphous powder √ Color : White √ Odor : Odorless √ Solubility : Soluble in dilute acids. Insoluble in water.

2. Na-CMC: Carmellose sodium

Carboxymethylcellulose Sodium is widely used in oral and topical pharmaceutical formulations, primarily for its viscosity-increasing properties.

Properties:

i. It occurs as a white to almost white ii. Odourless and tasteless iii. Granular powder iv. It is hygroscopic after drying v. Easily dispersed in water at all temperatures, forming clear, colloidal solutions.

The aqueous solubility varies with the degree of substitution.

Function: Suspending agent Stabilizing agent

Viscosity-increasing agent Water-absorbing agent

3. Glycerin:( Glycerol; Glycerine) Glycerin is used in a wide variety of pharmaceutical formulations including oral, otic, ophthalmic, topical, and parenteral preparations. Glycerin has preservative qualities and is often used as a stabilizer and as an auxiliary solvent in conjunction with water or alcohol. Properties: i. Clear, colorless, odorless iii. Viscous ii. Hygroscopic liquid iv. Sweet in taste (App. 0.6 times as sweet as sucrose) Functions: Solvent, Co-solvent Humectant

Antimicrobial preservative Viscosity increasing agent

Sweetening agent etard crystallization of sucrose R

4. Sorbitol Solution Sorbitol is D-glucitol. It is a hexahydric alcohol related to mannose and is isomeric with mannitol. Sorbitol: Sorbitol is widely used as an excipient in pharmaceutical formulations.

Md. Imran Nur Manik




Properties: i. Odorless, white or almost colorless iii. Crystalline ii. Hygroscopic powder iv. Sweet in taste Functions: Prevent crystallization of sugar around the cap of bottles Sweetener


5. Methyl & Propylparaben: (parabens : Alkyl esters of p-hydroxybenzoic acid ) Methylparaben is widely used as an antimicrobial preservative in cosmetics, food products, and pharmaceutical formulations.


i. Colorless crystals or a white crystalline powder ii. Odorless or almost odorless . iii. Slight burning taste.


6. Saccharine Sodium Saccharinum

Properties: i . White crystalline powder. ii. Odorless or faintly aromatic. iii. Efflorescent. SACCHARIN-Na SACCHARIN iv. It has an intensely sweet taste, with a metallic or bitter aftertaste. Functions: ♦ Sweetening agent (approximately 300–600 times sweet than sucrose). ♦ Saccharin sodium enhances flavor systems and may be used to mask some unpleasant taste characteristics. 7. Sodium Citrate (dihydrate) Trisodium citrate; C6H5Na3O7.2H2O

Properties: i. Monoclinic crystals or a white crystalline powder. ii. Odorless, colorless. iii. Cooling, saline (sour) taste. iv. It is slightly deliquescent in moist air and efflorescent in warm dry air. Functions: ♦ Buffering agent ♦ Sequestering agent ♦ Preservatives and Antioxidants ♦ Alkalizing agent ♦ Emulsifying agent ♦ Processing Aids and Additives

Md. Imran Nur Manik




Other ingredient(s) used: Peppermint Oil : It is used as flavouring agent. Green banana flavour

Indications: Antacid Suspension is indicated for-

Dyspepsia, Hyperacidity, Gastric and duodenal ulcer,

Gastritis; Relief of flatulence, Abdominal distention and

Windy colic.

Dosage & Administration: 1-2 teaspoonfuls one hour after meals and at bed time or as directed by the physician.

Warning & Precautions: Drugs containing Al(OH)3 shouldn’t be taken concomitantly with any form of Tetracycline, as the absorption of the later may be affected. Al(OH)3 may also reduce the absorption of Digoxin.

Side effects:

1. Theoretically, if the gastric pH is raised too much, acid rebound may occur, since an effort to maintain a lower pH, the stomach secretes additional HCl acid which consumes the antacid. 2. A second potential problem is systemic alkalosis. If the antacid is sufficiently water soluble and is composed of readily absorbable ions, the antacid may be absorbed and exert its alkaline effort on the body’s buffer system. 3. Another problem is sodium content of antacid. Those patients who are sodium restricted, diet should be advised of this when antacid is recommended. 4. The 4th side effect is the local effect is the GIT. Antacid containing calcium and aluminum salts, after being converted to soluble salt by gastric acid, tend to constipating, while containing magnesium salts tend to have a laxative effect.

Antacid Suspension

Each 5 mL contains 200 mg Aluminium Hydroxide &

200 mg Magnesium Hydroxide Gel

Batch No. : 0171740


Exp. Date : Oct 2019

M.R.P. Tk. : 67

Indication: Peptic Ulcer, Gastric Ulcer, Gastric acidity.

Dose : As directed by Physician

Storage condition: Keep in cool and dry place

Precaution : Shake before use.

Keep every medicine out of reach of children.

Store in cool and dry place. DAR No. : 025-0144-088

Mfg. Lic. No. :12 & 80


Market preparation: Antacid Suspension SL. Trade/Brand Name Manufacturer Dosage form 01 02 03 04 05

Md. Imran Nur Manik




Experiment No. 05

Name of the Experiment: Formulation and preparation of Metronidazole oral Suspension. (Each 5 ml contains Metronidazole Benzoate BP 320 mg equivalent to 200 mg Metronidazole.)

Introduction: Suspensions are biphasic liquid dosage form of medicament in which the finely divided solid particles ranging from 0.5 to 5 micron are suspended or dispersed in a liquid or semisolid vehicle. The vehicle may be aqueous or oily.

Suspensions represent a useful method of preparing drugs that are poorly soluble in acceptable solvents. They are formulated for all the major routes of administration, in particular the oral, parenteral and topical routes, with specific requirements for each route and desired response.

Metronidazole oral suspension is a suspension of Metronidazole Benzoate in a suitable flavoured vehicle.

Metronidazole is a nitroimidazole, has an extremely broad spectrum antiprotozoal and antimicrobial activities, with high activity against anaerobic bacteria and protozoa. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. Metronidazole benzoate

Some physical properties of a well formulated suspension

1. The suspension must remain sufficiently homogenous for at least the period between shaking the container and removing the required dose.

2. The sediment produced on storage must be easily re-suspended by the use of moderate agitation.

3. The suspension may be required to be thickened in order to reduce the rate of settling of the particles. The viscosity must not be so high that the removal of the product from the container and transfer to the site of application becomes difficult.

4. The suspended particles should be small and uniformly sized in order to give a smooth, elegant product free from a gritty texture.

Recipe: For 60 mL Metronidazole Suspension: Each 5 mL contains 320 mg Benzoyl Metronidazole (Metronidazole benzoate~Metronidazole 200 mg BP)

Then 60 mL contains 5

60320 mg of Benzoyl Metronidazole

= 3840 mg ~3.84 gm of Benzoyl Metronidazole Apparatus: 1. Beakers 2. Master & pestle 3. Funnel 4. Bottle 5. Measuring cylinder 6. Electric balance 7. Pipette

Md. Imran Nur Manik




Formula For 60 mL Metronidazole suspension:

Each 5 mL contain 320 mg of benzoyl metronidazole. (Metronidazole benzoate)

Name of Ingredient Theoretical weight Purpose Benzoyl Metronidazole BP 3.84 gm API. Imidazole antibacterial.

Na-CMC BP 0.5 gm Suspending agent.

Sucrose syrup BP 20 mL Sweetening agent.

Sorbitol Solution (70%) BP 5 mL Viscosity imparting agent; Humectant, Sweetener; Anti-crystallization agent.

Glycerin/Glycerol BP 5 mL Sweetener, Humectant, Retard crystallization of sucrose.

Methyl 4-Hydroxylbenzoate BP 100 mg / 0.1 gm Antimicrobial Preservative.

Propyl 4-Hydroxbenzoate BP 10 mg / 0.01 gm Antimicrobial Preservative.

Saccharine –Na BP 0.1 mg / 0.0001 gm Sweetening agent. 500 × more sweet than sucrose

Citric acid BP 100 mg / 0.1 gm Acidifying & buffering agent.

Na-Citrate BP 60 mg / 0.06 gm Flocculating & sequestering agent.

Propylene glycol 3 drops Wetting agent; Solvent; Humectant.

Organic flavor Q.S. Improving organoleptic property.

Organic color Q.S.

Distilled water Q.S. up to 60 mL Solvent/Vehicle.


1. Take 0.5 gm of Na-CMC in a clean & dry 50 mL beaker and add 15 mL DW. Carefully stir and allow for proper swelling to form a homogenous mucilage.

2. Take 3.84 gm Benzoyl Metronidazole in a 250 mL beaker and dissolve it in 5 mL propylene glycol with proper stirring. Then add the previously made Na-CMC mucilage (Step-1) in it.

3. Afterwards add 0.1 mg (0.0001 gm) Na-saccharine, 0.1 gm Methylparaben and 0.01 gm Propylparaben, 0.1 gm Citric acid & 0.06 gm Na- Citrate to this solution with proper trituration.

4. Later add 20 mL sucrose syrup, 5 mL sorbitol solution and 5 mL glycerin with continuous stirring to obtain proper homogeneous product.

5. Now add the organic flavor and color and mix them appropriately.

6. Transfer the whole content of beaker in a measuring cylinder and adjust the volume to 60 mL by the addition of purified water.

7. Finally transfer the preparation in an amber colored glass bottle since the metronidazole is light sensitive. Close & label the bottle properly.

Md. Imran Nur Manik




Functions of each ingredient:

1. Bezoyl Metronidazole: It is the active ingredient of the preparation. It is used in the treatment of infection caused by protozoa & flagella.

Properties: √ Physical form : Crystalline powder or Flakes √ Color : White, Slightly yellowish √ Odor : Odorless √ Nature : Acidic in nature √ pH : 5.6―6.5 √ Solubility : Freely soluble in methylene chloride, soluble in acetone, Slightly soluble in alcohol. Practically insoluble in water.

Function:

Metronidazole is also used in the treatment of infections caused by― Giardia lamblia, Trichomonas vaginalis, anaerobic cocci, and anaerobic gram-negative bacilli (for example, Bacteroides species)

It is the drug of choice for the treatment of pseudomembranous colitis caused by the anaerobic, gram-positive bacillus Clostridium difficile. 2. Na-CMC: (Carmellose sodium)

Carboxymethylcellulose Sodium is widely used in oral and topical pharmaceutical formulations, primarily for its viscosity-increasing properties.

Properties:

i. It occurs as a white to almost white ii. Odourless iii. Tasteless iv. Granular powder v. It is hygroscopic after drying vi. Easily dispersed in water at all temperatures, forming clear, colloidal solutions.

The aqueous solubility varies with the degree of substitution.

Function: Suspending agent Stabilizing agent

Viscosity-increasing agent Water-absorbing agent


Md. Imran Nur Manik




Properties: Colorless or Brown, Odorless, Crystalline Powder. Viscous in nature. It has a sweet taste. Free flowing (crystalline sucrose). Cohesive solid (Powder Sucrose). Melting Point: 160°C –186°C (with decomposition) Good stability at room temperature and at moderate relative humidity. Dilute sucrose solutions are liable to fermentation by microorganisms. Sucrose is also considered to be more cariogenic than other carbohydrates since it is more easily converted to dental plaque. For this reason, its use in oral pharmaceutical formulations is declining. Functions: ♦ Sweetening Agent: Used to enhance palatability. ♦ Viscosity imparting agent: Used to increase viscosity.

4. Sorbitol Solution Sorbitol is D-glucitol. It is a hexahydric alcohol related to mannose and is isomeric with mannitol. Sorbitol: Sorbitol is widely used as an excipient in pharmaceutical formulations. Properties: i. Odorless, white or almost colorless iii. Crystalline ii. Hygroscopic powder iv. Sweet in taste Functions: Prevent crystallization of sugar around the cap of bottles Sweetener


5. Glycerin:( Glycerol; Glycerine) Glycerin is used in a wide variety of pharmaceutical formulations including oral, otic, ophthalmic, topical, and parenteral preparations. Glycerin has preservative qualities and is often used as a stabilizer and as an auxiliary solvent in conjunction with water or alcohol. Properties: i. Clear, colorless, odorless iii. Viscous ii. Hygroscopic liquid iv. Sweet in taste (App. 0.6 times as sweet as sucrose) Functions: Solvent, Co-solvent Humectant

Antimicrobial preservative Viscosity increasing agent

Sweetening agent etard crystallization of sucrose R

6. Methyl & Propylparaben: (parabens : Alkyl esters of p-hydroxybenzoic acid ) Methylparaben is widely used as an antimicrobial preservative in cosmetics, food products, and pharmaceutical formulations.


i. Colorless crystals or a white crystalline powder ii. Odorless or almost odorless . iii. Slight burning taste.

Md. Imran Nur Manik





7. Saccharine Sodium Saccharinum

Properties: i . White crystalline powder. ii. Odorless or faintly aromatic. iii. Efflorescent. SACCHARIN-Na SACCHARIN

iv. It has an intensely sweet taste, with a metallic or bitter aftertaste. Functions: ♦ Sweetening agent (approximately 300–600 times sweet than sucrose). ♦ Saccharin sodium enhances flavor systems and may be used to mask some unpleasant taste characteristics. 8. Citric acid :( Citric acid monohydrate) 2-Hydroxypropane-1,2,3-tricarboxylic acid monohydrate. Properties: i. Colorless or translucent crystals or granules, /or as a white crystalline powder. ii. Odorless. iii. Strong acidic taste. iv. Efflorescent. v. It is slightly deliquescent in moist air. vi. Melting point 100°C (Monohydrate), 153°C (anhydrous).

Functions: ♦ Buffering agent (adjust the pH of solutions) ♦ Sequestering agent ♦ Acidifying agent ♦ Sialogogue An agent increasing the flow of saliva. ♦ Flavor enhancer ♦ Antioxidant synergist.

9. Sodium Citrate (dihydrate) Trisodium citrate; C6H5Na3O7.2H2O

Properties: i. Monoclinic crystals or a white crystalline powder. ii. Odorless, colorless. iii. Cooling, saline (sour) taste. iv. It is slightly deliquescent in moist air and efflorescent in warm dry air. Functions: ♦ Buffering agent ♦ Sequestering agent ♦ Preservatives and Antioxidants ♦ Alkalizing agent ♦ Emulsifying agent ♦ Processing Aids and Additives

Md. Imran Nur Manik




10. Propylene Glycol Propylene glycol is a useful solvent with a wide range of applications and is frequently substituted for glycerin in modern pharmaceutical formulations. Properties: i. Clear, colorless, practically odorless iii. Viscous ii. Hygroscopic in nature iv. Usually tasteless (/faintly sweet) Functions: ♦ Solvent or co-solvent (Oral , Parenterals, Topical, Aerosol) ♦ Disinfectant ♦ Antimicrobial preservative (Solutions, Semisolids) ♦ Humectant (Topical) 11. Flavouring agent: Lemon flavour & Bergamot flavor

Indications: It is also used to treat-

Urogenital trichomoniasis in the female and male, Giardiasis, (amebiasis SYN: Amebic dysentery)

Anerobic bacterial infections, Intestinal and extra-intestinal amebiasis

Metronidazole is an alternative to penicillin for the treatment of many oral infections. Cautions & Side-effects of Metronidazole: Some side effects of Metronidazole include –

Gastrointestinal discomfort, Nausea, Coated tongue, headache Dryness of mouth and unpleasant metallic or bitter taste. It should not be used- during pregnancy, breast-feeding, in patients with blood dyscrasia.

Dose: For amebic dysentery-

Adult & Children over 10 years: 800mg tid (2g once daily)

Children 7-10 years:400mg tid Children 3-7 years:200mg qid Children 1-3 years:200mg tid

Metronidazol Suspension

Each 5 mL contains Metronidazole BP 200mg

Batch No. : 0171740


Exp Date : Oct 2019

M.R.P. Tk. : 67

DAR No. : 025-0144-088

Indication : Antiprotozoal, Antibacterial

Dose : As directed by Physician

Storage : Keep in cool and dry place

Precaution : Suspension should be taken at least

one hour before a meal.

Shake before use.

Keep every medicine out of reach of children.

Mfg. Lic. No. :12 & 80


Market preparation: Metronidazole Suspension SL. Trade/Brand Name Manufacturer Dosage form 01 02 03 04 05

Md. Imran Nur Manik




Experiment No. 06

Name of the Experiment: Formulation and preparation of Preparation of oil in water (O/W) emulsion. (Each 5 mL contains 0.5 mL castor oil)

Introduction An emulsion may be defined as a dispersion of two immiscible liquids, in which the dispersed phase is finely subdivided and uniformLy distributed as droplets throughout the dispersion medium with the aid of an emulsifying agent that achieves emulsification and maintains stability. The liquid dispersed into small droplets is called the dispersed, internal, or discontinuous phase. The other liquid is the dispersion medium, external phase, or continuous phase. Emulsion is widely used in pharmacy and medicine. Emulsions may be employed orally, topically, or parenterally, depending on the formulation ingredients and the intended application. They are made internally as well as externally, certain medicinal agent having an unpleasant taste & odour can be made more palatable for oral administration in the form of emulsion. The activity of certain drugs can be increased & action can be prolonged by emulsifying the drug in a suitable vehicle. Castor oil has been used as a stimulant laxative to relieve occasional constipation. However, castor oil usually is avoided for simple constipation because it produces violent purgation.

Classification of Emulsion: There are two types of emulsion a) Oil in water (o/w) type emulsion and b) Water in oil (w/o) type emulsion

Oil in water (O/W) type emulsion:

In oil in emulsion, the oil is the dispersed phase and water is the dispersion medium. This type of emulsion is preferable or preferred for internal use because the unpleasant taste & odour is masked by emulsification. The aqueous phase constitutes> 45% of the total weight. Water in oil (W/O) type emulsion: In water in oil emulsion, the water is the dispersed phase and oil is the dispersion medium. This type of emulsion is mainly used externally. The aqueous phase constitutes < 45% of the total weight. According to the consistence:

a) Liquid emulsion: They are generally oil in water emulsion and they are used orally, parentally and externally. e.g. lotion, ointment.

b) Semi-solid emulsion: They are both o/w and w/o type of emulsion. They are used as internally and externally. e.g. cream.

According to the route of administration:

a) Emulsion for internal use. & b) Emulsion for external use. According to the particle size:

a) Coarse emulsion b) Fine emulsion c) Micro emulsion

Md. Imran Nur Manik




Preparation of Emulsion: For small scale preparation, emulsion can be prepared by the following method: a) Dry gum method b) Wet gum method c) Bottle method The proportion of oil, water and gum acacia required for fixed oil and volatile oil for the preparation of primary emulsion are- Name of the oil – Rose oil : Water : Gum Fixed oils – 4 : 2 : 1 Volatile oils – 4 : 4 : 2 Formula or Recipe: For 100 mL Castor oil Emulsion

Each 5 mL emulsion contains 0.5 mL of castor oil Name of ingredient Theoretical weight Purpose Castor oil 10 mL API . Cathartics and Laxatives Acacia 2.5 gm Emulsifying agent. Sugar syrup 10 mL Sweeting agent. Methylparaben 0.2 gm Preservative. Sorbitol solution 10 mL Sweetening agent. Raspberry oil 1-2 drops or Q.S. Flavouring agent. Distilled water Q.S. to 100 mL Vehicle. Apparatus:

1. Mortar and pestle 3. Bottle 4. Measuring cylinders 2. Beakers 5. Filter papers 6. Funnel 7. Droppers 8. Stirrers


1. Take thoroughly cleaned and completely dried mortar and pestle. Transfer accurately weighed 2.5 mg acacia in the mortar.

2. Slowly triturate the acacia by adding small quantity of purified water to obtain uniform mucilage. 3. Now add 10 mL castor oil in small portions with rapid trituration in one direction until a clicking sound is produced and the product become white or nearly white. At this stage, the emulsion is known as primary emulsion. Later add Methylparaben to the emulsion.

4. Afterwards add 10 mL sugar syrup and 10 mL sorbitol in small quantities at a time with constant unidirectional trituration so as to get homogeneous product.

5. Transfer the emulsion in a measuring cylinder and add more vehicles with gentle stirring to produce the final volume 100 mL.

6. After the formation of a uniform emulsion, transfer the preparation in a bottle, close and label the bottle properly.

Md. Imran Nur Manik




Functions of ingredient:

1. Castor oil : It is the active ingredient of the preparation. It acts as a laxative.

2. Acacia: Properties: i. Acacia is available as white or yellowish-white thin flakes, spheroidal tears, granules, powder, or spray-dried powder. ii. Odorless. iii. Bland taste.

Functions: ♦ Emulsifying agent ♦ Stabilizing agent ♦ Suspending agent ♦ Viscosity-increasing agent.


Properties: Colorless or Brown, Odorless, Crystalline Powder. Viscous in nature. It has a sweet taste. Free flowing (crystalline sucrose). Cohesive solid (Powder Sucrose). Melting Point: 160°C –186°C (with decomposition) Good stability at room temperature and at moderate relative humidity. Dilute sucrose solutions are liable to fermentation by microorganisms. Sucrose is also considered to be more cariogenic than other carbohydrates since it is more easily converted to dental plaque. For this reason, its use in oral pharmaceutical formulations is declining. Functions: ♦ Sweetening Agent: Used to enhance palatability. ♦ Viscosity imparting agent: Used to increase viscosity.

imparting agent: Used to increase viscosity.

4. Methylparaben:


i. Colorless crystals or a white crystalline powder ii. Odorless or almost odorless. iii. Slight burning taste.

Functions: i. Methylparaben exhibits antimicrobial activity of pH 4–8. ii. More active against Gram-positive than against Gram-negative bacteria. iii. Activity may be improved by using combinations of parabens, as additive effects occur.

Md. Imran Nur Manik




5. Sorbitol Solution Sorbitol is D-glucitol. It is a hexahydric alcohol related to mannose and is isomeric with mannitol. Sorbitol: Sorbitol is widely used as an excipient in pharmaceutical formulations. Properties: i. Odorless, white or almost colorless iii. Crystalline ii. Hygroscopic powder iv. Sweet in taste Functions: Prevent crystallization of sugar around the cap of bottles Sweetener


6. Raspberry oil : As a flavoring agent.

7. Distilled water : It is used as a vehicle. Other ingredients that can be used: ♦ Active ingredients : Arachid oil can be used. ♦ Emulsifying agent : Agar, tragacanth, and starch ♦ Sweetening agent : Sucrose can be used. ♦ Preservative : Na-benzoate and Propylparaben. ♦ Flavouring agent : Peppermint oil, lemon oil and clove oil can be used.

Importance of emulsion in pharmacy and medicine:

1. The activity of certain drugs can be increased and action can be prolonged by emulsifying the drug in a suitable vehicle.

2. Certain medicinal agent having the unpleasant odour and taste can be more palatable for oral administration in the form of emulsion.

Dose Pediatric Patients: Constipation- Use in children for occasional constipation generally is avoided.

Adults: Constipation (Oral)~ 15 mL, but rarely indicated for occasional constipation. Colonic Evacuation (Oral)~ 15–60 mL about 16 hours before the surgery or procedure. Contraindications It should not be used-

In acute abdominal pain, nausea, vomiting, or other symptoms of appendicitis or undiagnosed abdominal pain or rectal bleeding.

Intestinal obstruction.

Pregnancy or menstruation. Warnings/Precautions

Potentially serious toxicity with chronic use.

Md. Imran Nur Manik




Common Adverse Effects

Abdominal discomfort, Nausea, Cramps,

Griping, and/or Faintness, Excessive irritation of the colon and violent purgation,

Diarrhoea, Fluid and Electrolyte depletion and GI irritation.

Castor oil emulsion 100 mL Each 5 mL contains 0.5 mL of castor oil Batch No. : 0171740 Mfg. Date : Oct 2017 Exp Date : Oct 2019 M.R.P. Tk. : 67 DAR No. : 025-0144-088 Mfg. Lic. No. : 12 & 80

Indication: Cathartic. Dose: As directed by Physician. Storage condition: Keep in cool and dry place. Precaution: Shake before use. The emulsion may be mixed with 120–240 mL of water, milk, fruit juice, or soft drink before administration Administer orally. Keep every medicine out of reach of children.


Bibliography:

1) Rowe RC et al. eds (2009). Handbook of Pharmaceutical Excipients, 6th edn. Washington

DC: American Pharmaceutical Association.

2) Linda A. Felton. eds (2013). Remington: Essentials of Pharmaceutics 1st edn. Pharmaceutical Press, Lambeth High Street, London SE1 7JN, UK.

3) British Pharmacopoeia eds (2013). 151 Buckingham Palace Road ; London SW1W 9SZ.

4) British National Formulary eds (2013) 58th edn. BMJ Group and RPS Publishing; Tavistock Square, London WC1H 9JP, UK and 1 Lambeth High Street, London, SE1 7JN, UK.

5) Lachman L et al. eds (1986). The Theory and Practice of Industrial Pharmacy, 3rd edn.

Philadelphia: Lea & Febiger.

6) Loyd V., Nicholas G. and Howard C. Ansel. eds (2011). Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems., 9th edn. Philadelphia PA/ Baltimore, MD: Wolters Kluwer Health/Lippincott Williams & Wilkins.

7) David S. Jones. eds (2008). FASTtrack: Pharmaceutics – Dosage Form and Design. 1st edn. Pharmaceutical Press, Lambeth High Street, London SE1 7JN, UK.

8) ACETAMINOPHEN-http://www.chemicalland21.com/lifescience/phar/ACETAMINOPHEN.htm

Md. Imran Nur Manik

http://www.chemicalland21.com/lifescience/phar/ACETAMINOPHEN.htm




Appendix- Brief description

LAB-01: Acetaminophen is known as a non-aspirin pain reliever. Acetaminophen is a

nonprescription analgesic and antipyretic drug similar to aspirin. But acetaminophen is not an

NSAID (Nonsteroidal Antiinflammatory Drug) as it doesn't participate in the inflammatory response

as it can not inhibit cyclooxygenases in the presence of peroxides.

LAB-01: Sucrose syrup s.g. 1.31g/mL (85% w/V ) 100 mL = 131 gm which contains 85 gm

sucrose USP is denser than bp. Syrup has a specific gravity of about 1.313, which means that each

100 mL of syrup weighs 131.3 g. Because 85 g of sucrose is present, the difference between 85

and 131.3 g, or 46.3 g, represents the weight of the purified water.

LAB-01: Methylparaben is the least active of the parabens; antimicro-bial activity increases with

increasing chain length of the alkyl moiety. Activity may be improved by using combinations of

parabens as synergistic effects occur. Therefore, combinations of methyl-, ethyl-, propyl-, and

butylparaben are often used together. Activity has also been reported to be enhanced by the addition

of other excipients such as: propylene glycol (2–5%); phenylethyl alcohol; and edetic acid.

Solubility 25°C

Meth-P is less lipophilic more hydrophilic (Water :1 in 400 & Mineral oil: Practically insoluble &

Ether 1 in 10). Thus suitable for preventing the Gr+ve bacteria.

Pro-P is more lipophilic less hydrophilic (Water:1 in 4350 & Mineral oil 1 in 3330 Ether: Freely

soluble).

Thus suitable for preventing the Gr-ve bacteria (Gr-ve bacteria contains

lipopolysaccharide in outer membrane). Thus combination encompasses a broad

spectrum of bacteria.

Urticaria (u˘ r-tı˘-ka￣ _re￣-a˘ ) [L. urtica, nettle] An allergic reaction marked

by multiple discrete swellings on the skin (wheals) that are intensely itchy and last

up to 24 hr. The wheals appear primarily on the chest, back, extremities, face, or

scalp. SYN: hives.

Pruritus (proo-rı¯tu˘ s ) [L., itching] Itch; a tingling or faintly burning skin sensation

that prompts a person to rub or scratch. It may be a symptom of a disease process, such as an allergic

response or hyperbilirubinemia, or it may be due to emotional factors.

Md. Imran Nur Manik

www.pharmacydocs.blogspot.com

Date post:	15-Mar-2018
Category:	Health & Medicine
Upload:	imran-nur-manik
View:	172 times
Download:	14 times

Pharmaceutical Technology-I Lab MANIK

Health & Medicine