Pharmaceutical oral solutions A

Pharmaceutical oral solutions A

1. PHARMACEUTICAL ORAL SOLUTION Pharmaceutics-IIB (Dosage Form Science Lab) Pharm 406 “GROUP NO. 5 A” Submitted to: Ma’am Tehmina Adnan Submitted by: Aleeza Rashid (R-0 08 ), CMS: 112 -2019 Hafiza Ameema (R-0 28 ), CMS: 108 -2019 Nashia Farid (R-0 64 ), CMS: 114 -2019 Sara Ishaque Shaikh (R-0 78 ),CMS: 117 -2019 Taqdees Sohail (R-0 94 ), CMS: 111 -2019

2. INTRODUCTION DOSAGE FORMS: There are four types of dosage forms: 1- Solid 2- Semi solid 3- Liquid 4- Gaseous LIQUID DOSAGE FORM: Liquid dosage forms are essential pharmaceutical products which involves a mixture of active components and excipients. ROUTES OF DRUG ADMINISTERATION: Routes of drug delivery Parenteral Oral Oral cavity Topical Pulmonary Otic (ear) Nasal Ocular Vaginal Rectal

3. CLASSIFICATION OF LIQUID DOSAGE FORM: Classification of liquid dosage form Monophasic liquid dosage form Biphasic liquid dosage form Internal use External use Internal use External use Elixir Mouth: Syrup Gargles Linctus Mouth washes Oral lavage solution Skin: Oral rehydrating solution Lotions, Liniments Parenteral Others: Nasal drops Ear drop Suspension Emulsion

4. MONOPHASIC LIQUID DOSAGE FORMS: Monophasic liquid dosage form contains two or more components in one phase system . It is represent by true solution . ● A true solution is a clear homogenous mixture that is prepared by dissolving solute in a suitable solvent. MONOPHASIC LIQUID DOSAGE FORM FOR ORAL USE: Elixirs Syrups Linctuses Oral Rehydrating Solutions (ORS) Oral lavage solutions Gargles Mouth washes

5. PHARMACEUTICAL SOLUTIONS : Solutions are liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents. ● Most solutions intended for oral administration contain flavorants and colorants to make the medication more attractive and palatable. When needed, they may also contain stabilizers to maintain the chemical and physical stability of the medicinal agents and preservatives to prevent the growth of microorganisms in the solution. ● Pharmaceutical solutions are preparations in which the solid solutes, i.e. drug and excipients , are dissolved in a liquid solvent system. ● Solutions can be prepared by simple mixing of the solutes with the solvent system. In industry, solutions are prepared in large mixing vessels.

6. ADVANTAGES AND DISADVANTAGES OF PHARMACEUTICAL SOLUTIONS ADVANTAGES ● The drug is already dissolved in the solvent system; hence drug action can be rapid, allowing its use in emergencies. ● The drug immediately available for absorption. ● Solutions provide dose uniformity. ● Oral solutions are easily swallowed. ● Solutions are generally easier to manufacture than other dosage forms. DISADVANTAGES ● Many drugs are inherently unstable, and instability is increased when a drug is present in solution (i.e. as molecules). ● Many drugs are poorly soluble in water. Their formulation as a solution is challenging. ● Liquids are bulky and less easy for the patient to carry (e.g. the daily dose) than solid dosage forms. Liquids are also more expensive to transport, which increases the medicine’s cost. ● Oral solutions can undergo the process of liver first pass metabolism which decreases the bioavailability. ● The packaging of pharmaceutical solutions requires materials of higher quality.

7. THE SOLVENT SYSTEM: AQUEOUS SYSTEM: ● The majority of pharmaceutical solutions are water based. Water is the most commonly used solvent due to its many advantages, such as its lack of toxicity and low cost. ● For non parenteral solutions Potable (drinking) water is purified, for example, by distillation, ion exchange or reverse osmosis to produce ‘Purified Water’. ● For parenteral solutions , potable water is further purified to remove pyrogens (water-soluble, fever-producing compounds) producing ‘Water for Injections’. ● In extemporaneous dispensing , potable water, freshly drawn from a mains supply and/or purified water, freshly boiled and cooled, can be used to prepare oral or external solutions. ● Water does not dissolve many drug compounds to a sufficient degree to enable the preparation of a pharmaceutical solution. Other water-miscible liquids with greater ability to dissolve drugs may therefore be added to water to enhance drug solubility. These liquids are called cosolvents . Commonly used examples include glycerol, propylene glycol, ethanol and polyethylene glycol. COSOLVENTS: Cosolvents are generally less innocuous than water, and the concentration used in an aqueous solution is limited primarily by their toxicity , by drug solubility in the formulation and cost .

8. NON AQUEOUS SYSTEM: ● Nonaqueous solvent systems are used when the drug is insufficiently soluble or stable in aqueous systems, or when a solution is intended for specific properties, such as sustained drug absorption. ● Nonaqueous solutions are limited to certain delivery routes , such as oral, intramuscular and topical, due to their toxicity, irritancy or immiscibility with physiological fluids. ● There are huge number of organic liquids in which drugs can dissolve, the majority are toxic, and consequently only a few are used in pharmaceutical solutions. ● Examples of commonly used organic liquids are alcohols, esters, dimethyl sulfoxide etc. These liquids are used as cosolvents with water, as cosolvents with other organic liquids, or on their own. DRUG: The drug may be a low molecular weight such as aspirin, or a large biotherapeutic molecule, such as insulin or an antibody. It is present in a solution as molecules or ions throughout the solvent. It is usual to ensure that the drug concentration in a pharmaceutical solution is well below its saturation solubility. EXCIPIENTS: ● Excipients are substances other than the drug or prodrug which are included in pharmaceutical solutions. ● These are used for a number of reasons, such as to enhance product stability, bioavailability or patient acceptability, or to aid product manufacture and/or identification. ● The excipient must be nontoxic, nonsensitizing and nonirritating , as well as compatible with all the other components of the formulation. ● The route of administration is important because many excipients are acceptable by certain, but not all, routes.

9. EXCIPIENTS USED IN PHARMACEUTICAL SOLUTIONS: EXCIPIENTS EXAMPLES OF EXCIPIENTS CO-SOLVENTS Ethanol, glycerol, propylene glycol. FLAVOURING AGENTS Used to mask the taste of drugs. E.g. vanilla, raspberry, orange oil, and lemon oil are used for oral solutions and Menthol is used in both oral and nasal solutions. COLORING AGENTS A coloring agent should correlate with the flavouring agent. E.g. green with mint flavor. SWEETNERS Used to improve the palatability of oral solutions. E.g. sucrose, sorbitol, mannitol. ANTIMICROBIAL PRESERVATIVES Used to preserve multidose preparations. E.g benzyl alcohol, combination of parabens (methyl, propyl, butyl). ANTIOXIDANTS Used to stabilize solutions. E.g. Sodium metabisulfite, sodium sulfite, ascorbic acid. CHELATING AGENTS Used to increase solution stability. E.g. Disodium edetate pH ADJUSTERS Acids: E.g. citric acid, buffers. Alkalis: E.g. sodium hydroxide, buffers. ISOTONICITY ADJUSTERS Sodium chloride, potassium chloride, mannitol. VISCOSITY ENHANCERS Hypromellose, hydroxyethylcellulose, poly(vinyl alcohol), dextran.

10. SOLUTION STABILITY: A pharmaceutical solution must be stable for the duration of its shelf life (period of storage and use). That is, it must retain the same physical, chemical, microbiological, therapeutic and toxicological properties that it possessed at the time of its manufacture. Pharmaceutical solutions are therefore formulated at the pH favouring drug stability, and often include excipients to enhance product stability. ● To reduce photooxidation , solutions are packaged in containers that do not allow light transmission. ● To reduce oxidation , antioxidants and/or metal chelators (as heavy metal ions catalyse oxidation) are used. ● To inhibit microbial growth during use, preservatives are used in multidose products. In addition, the excipient must remain in the solution throughout the shelf life of the product. That is, the concentration of the excipient must not decrease. DISSOLUTION: Dissolution is the time-dependent process of a drug dissolving into a solvent to form a solution. Dissolution is typically the first step in absorption of a drug and is a critical factor in the drug’s bioavailability . Dissolution is an extrinsic property which means that dissolution can be modified through changes to the ● Drug’s particle size distribution ● Surface characteristics s ● Solid-state, or ● through inclusion of certain excipients.

11. A drug may also be categorized in terms of relative solubility , where solubility is the parts of solvent required to dissolve 1 part of solute (drug).USP defines solubility qualitatively as described below; USP term Solvent p arts required to dissolve 1 part of solute / drug Solubility (mg/mL) Very soluble Less than 1 >1000 Freely soluble 1–10 100–1000 Soluble 10–30 30–100 Sparingly soluble 30–100 10–30 Slightly soluble 100–1000 1–10 V. Slightly soluble 1000–10,000 0.1–1 Practically insoluble Greater than 10,000 <0.01 If the aqueous solubility of drug at selected pH of formulation is ; high therapeutic drug is incorporated into vehicle &formulated as oral sol. moderate solubility of drug in sol. must be enhanced using co-solvents. low The difference between aqueous solubility of drug & required conc. is too great to the use of co-solvents or surfactants in the solubilized form & toxic when administered orally. Therefore drug is to be formulated as a suspension In case of liquid–liquid solutions, solubility is defined in terms of miscibility . In liquid solvents, It exists in 2 states: Completely miscible or partially miscible "The maximum amount of the drug that can be dissolved in a solvent at a specific temperature and pressure.” DRUG SOLUBILITY “it is the ability of one liquid to mix (or dissolve) in another liquid.”

12. FACTORS INFLUENCING SOLUBILITY DRUG’S PHYSICOCHEMICAL PROPERTIES Solubility of drug molecules in a solvent are dependent on several physicochemical properties, including molecular weight, volume, density, and number of hydrogen bonds . Particle size ∝ 1/rate of solubility. solubility of a chemically related drugs ∝ 1/ melting points of the drugs Solubility of a drug is directly affected by the type of chemical substituent groups . Solubility of drugs containing hydrophilic groups > those containing lipophilic substituent groups TEMPERATURE In most drug compounds having positive heat of solution ; solubility ∝ temperature. In cases, where drug may have negative heat of solution; addition of heat decreases its solubility. pH and pKa Solubility of therapeutic agents is pH-dependent as majority are either acids or bases. pKa of the drug is also important as it determines degree of ionization of drug at a specific solvent pH. Solubility of acids & bases ∝ degree of ionization. When solubility decreases with addition of an electrolyte salting-out . If solubility increases with addition of an electrolyte salting-in . The solubility of acidic compounds increases as the pH of the sol. is increased ( above the pKa) & solubility of basic compounds increase as pH is lowered ( below the pKa) POLARITY Solubility follows the rules of “like dissolves like.” Polar substances solubilize in polar solvents ( water & ethanol ) through dipole–dipole interactions & hydrogen bonding , Nonpolar substances solubilize in nonpolar solvents ( chloroform, Conc. acid or alkali ) through Van der Waals interactions . Equally, the organic bases more soluble in organic solvents than the corresponding salt forms.

13. Nature of the solubility enhancer depends on; Drug molecule ,Route of administration, Intended patient population . METHODS TO ENHANCE THE SOLUBILITY PHYSICAL MODIFICATIONS Particle size reduction increased surface area Complexation is the interaction of a poorly soluble therapeutic agent with an organic molecule, (e.g. surface-active agents, hydrophilic polymers) to generate a soluble intermolecular complex.   Solubilization by surfactants lowered the surface tension. CHEMICAL MODIFICATIONS Salt formation Among the therapeutic agents available in salt form, drug salt with required solubility in dosage form can be easily selected Optimization of pH The acceptable pH range for oral sols is large, ranging from 5 to 8 pH units. For organic solutes that are ionizable, changing the pH of the system is the simplest and most effective means of increasing aqueous solubility.  Use of buffer Buffer maintains the pH of the solution overtime and it reduces or eliminate the potential for precipitation upon dilution. On dilution pH alteration occurs that decrease solubility. OTHER METHODS Co-solvency Co-solvents are liquid components prepared by mixing miscible or partially miscible solvents & used to enhance solubility of poorly soluble drugs. E.g. glycerol, propylene glycol, ethanol and polyethylene glycol etc. Cosolvent system reduces the interfacial tension between the aqueous solution &hydrophobic solute.  Choice of co-solvent for a particular formulation involves consideration of solubility of therapeutic agent in vehicle, toxicity of vehicle & cost of formulation.  

14. ELIXIRS

15. ELIXIRS TYPES OF ELIXIRS Non Medicated Elixir employed as vehicle & used in extemporaneous filling involving Medicated Elixir employed for therapeutic effect of the drug they contain “Elixirs are clear, sweetened hydro-alcoholic solutions intended for oral use and are usually flavored to enhance their palatability.” E.g. Antihistamine Elixirs Barbiturate Sedative and Hypnotic Elixirs Phenobarbital Elixir Digoxin Elixir Addition of a therapeutic agent to a pleasant tasting vehicle Dilution of an existing medicated elixir E.g. Aromatic elixir, Iso-alcoholic elixir, compound benzaldehyde elixir

16. TYPES OF MEDICATED ELIXIRS COMMERCIAL PRODUCT USES Brand: Benadryl Allergy Generic: (Diphenhydramine Elixir)  Provides fast, effective symptom relief from allergies and allergic reactions : Skin Itch, Sneezing, Itchy throat, watery eyes, Itchy, runny nose, Hives. COMMERCIAL PRODUCT USES  Brand: Welldorm Generic :(Chloral hydrate)   Short term pediatric treatment of insomnia . May also be used as a sedative before a procedure or test & or to reduce pain and anxiety after surgery. Antihistamines elixirs are useful primarily in the symptomatic relief of certain allergic disorders. Side effects: most common untoward effect is sedation . Other common adverse effects include dryness of the nose, throat, and mouth; dizziness; and disturbed concentration. Barbiturates are sedative and hypnotic agent that use to produce various degree of CNS depression. They’re administered in; small doses (daytime) as sedatives to reduce restlessness and emotional tension. Greater doses (before bed time) as hypnotics to release insomnia. Side effects: Large dose increases the effect from sedation to hypnosis to respiratory depression , leading to death due to fatal barbiturate over dosage. Barbiturates are classified according to the duration of their hypnotic effect .i.e. i. Long acting i.e. Phenobarbital , ii. Intermediate acting i.e. Amobarbital , iii. Short acting i.e. Secobarbital, iv. Ultra short acting i.e. Thiopental ANTIHISTAMINES ELIXIRS BARBITURATE SEDATIVE/HYPNOTIC ELIXIRS

17. TYPES OF MEDICATED ELIXIRS COMMERCIAL PRODUCT USES  Brand: Debritone Elixir Generic: (Phenobarbitone)  Used as an Anticonvulsant & sedative . It help control certain kinds of seizures & treat sleep problems,insomnia. COMMERCIAL PRODUCT USES  Brand: Lanoxin PG Elixir Generic: (Digoxin)  Increases force of myocardial infarction. Used in CFC, A trial fibrillation and other cardiac conditions Digoxin is a cardio tonic glycoside obtained from the leaves of Digitalis lanata . It is white crystalline powder that is insoluble in water but soluble in dilute alcohol solutions. It is required to contain 4.5 to 5.25 mg of digoxin per 100 ml of elixir or about 0.25 mg per 5 ml teaspoon. Digoxin is poisonous and its dose must be carefully determined and administered to each individual patient. Official elixir contains about 10% alcohol. Phenobarbital elixir, a long acting barbiturate is formulated to contain phenobarbital 0.4% ,which provides about 20 mg of drug per teaspoonful (5mL)of elixir, with a duration of action of 4-6 hours . Official elixir contain 14% alcohol which is use to dissolve phenobarbital. A usual dose as a sedative of about 30mg and hypnotic dose of about 100mg. PHENOBARBITAL ELIXIR DIGOXIN ELIXIR

18. FORMULATION/ COMPOSITION Note : Elixirs containing more than 10 to 12% of alcohol are usually self-preserving and do not require the addition of an antimicrobial agent.

19. PREPARATION

20. Elixirs usually contain 5-40% alcohol. Individual monograph instructions are followed for alcohol determination It is suitable for examining most fluidextracts ,tinctures and elixirs provided the capacity of the distilling flask is sufficient (commonly 2to 4times the volume of the liquid to be heated) and the rate of distillation is such that clear distillates are produced. Cloudy distillates can be clarified by agitation with talc, or calcium carbonate filtration. After, temperature of the filtrate is adjusted & the alcohol content determined from the specific gravity. During all operations, take precautions to minimize the loss of alcohol by evaporation. Viscosity measurement is a highly important quality control test incase of syrups &elixirs. Viscosity is a property of liquids directly related to the resistance to flow. Viscosity & consistency directly proportionate with stability of solutions & may be measured through various methods; U tube, Capillary tube Viscometer, Rotating viscometer method etc. QUALITY CONTROL TESTS FOR ELIXIRS DRY ELIXIRS Dry Elixirs can be produced by dissolving a solution of water-soluble dextrin and drug in an ethanol-water cosolvent system & spray-drying it. This type of dosage form may be useful to increase: Solubility, Dissolution & Bioavailability of the drug DETERMINATION OF ALCOHOL CONCENTRATION 2. VISCOSITY MEASUREMENT

21. ELIXIR Elixirs containing 10-12% alcohol are self-preserving . Better able to maintain both water-soluble and alcohol-soluble components in solution. Has stable characteristics. Easily prepared by simple solution. Easily administered in patients having problem of swallowing solid dosage form. Used as a vehicle . Used for dilution of medicated elixirs. Contains alcohol, can be vicious to children and adults who avoid alcohol. Less effective than syrups in masking taste of medicated substances. Because they contain volatile materials, it must be stored in a air-tight screw-top jar to avoid their escape. Needed to keep away from sources of ignition. ADVANTAGES DISADVANTAGES

22. CHOICE OF CONTAINER STORAGE CONDITIONS PATIENT COUNSELLING Plain amber medicine bottle with CRC, Suggested discard date for most elixirs is about 4 weeks. Keep below 30°C (at room temperature). Container should be tightly closed. Keep in light resistant amber color container; Protect from direct sunlight. LABELLING REQUIREMENTS The functions of a label are to indicate clearly: The contents of the container How & when the medicinal product should be taken &used How product should be stored & for how long Any warnings or cautions the patient needs to be made aware of Always use the medicine exactly as described in the leaflet or as your doctor or pharmacist has told you. After use, wipe the neck of the bottle with a clean damp cloth, which will remove any liquid left before putting the cap back on. Do not drink alcohol while you are taking the Elixir as it can affect the way the medicine works. Talk to your doctor or pharmacist before taking this medicine if you are pregnant, might become pregnant, or think you may be pregnant. You should not take Elixir if you are breast-feeding , because small amounts may pass into mothers’ milk which can be harmful to your baby. You may feel drowsy or sleepy while taking this medicine or in the morning after taking this medicine. If this happens, do not drive or use any tools or machines. If you feel the effect of your medicine is too weak or too strong, do not change the dose yourself, but ask your doctor.

23. SYRUPS

24. SYRUPS “ Syrups are concentrated aqueous preparations of a sugar or sugar substitute with or without flavoring agents and medicinal substances ” . TYPES OF SYRUPS Sucrose is the sugar employed most frequently in syrups but in special circumstances such as for diabetic patients and others whose diet is restricted to non-glycogenetic substances (methyl cellulose). Sucrose may be replaced to make non sucrose based syrups. (sorbitol, Glycerin, propylene glycol). The characteristic body that sucrose and alternative agents tends to impart to syrup is the result of achieving the proper viscosity. Pharmaceutical preparation that is made with this consistency along with sweetness and flavors have ability to mask the taste of added medicaments . Medicated Syrups Syrup s containing medicinal substances e.g. Cough syrup. Non Medicated Syrups Syrups containing flavoring agents but not medicinal substances are called non-medicated or flavored vehicles (syrups). Usually used in extemporaneous preparation e.g. Cherry syrup Simple Syrups It is a solution of 85% w/v sucrose dissolved in purified water (USP) e.g. Sucrose syrup.

25. TYPES OF MEDICATED SYRUP Analgesic Paracetamol, (Mepridine HCL) USES : Paracetamol is commonly used for its analgesic and antipyretic effects. Anticonvulsant Depakene syrup (Sodium valproate) USES : Sole or adjunctive therapy in simple, complex absence seizure disorder TYPES OF NON MEDICATED SYRUP Cherry syrup Sucrose based syrup with cherry juice 47% by vol. Acidic Ph makes it useful as a vehicle for drugs requiring acidic medium. Cocoa syrup Suspension of cocoa powder in aqueous vehicle sweetened and thickened with sucrose. Effective in administering bitter tasting drug to children.

26. COMPONENTS OF SYRUP In addition to the purified water and any medicinal agents present: In addition to these, syrups may contain special solvents, solubilizers, thickeners and stabilizers. PREPARATION OF SYRUPS Solution of ingredients with the aid of heat. Solution of ingredients by Agitation without aid of heat. Addition of sucrose to a medicated or flavored liquid. Percolation of either the source of medicating substance or of the sucrose. Sugars Usually Sucrose or sugar substitute used to provide sweetness and viscosity . Anti microbial preservatives benzoic acid 0.1% to 0.2%, sodium benzoate 0.1% to 0.2%, and methyl parabens, propyl parabens, and butyl parabens totaling about0.1%. Flavorants May be synthetic or naturally occurring such as volatile oils, vanillin etc. Colorants a coloring agent that correlates with the flavorant employed(i.e., green with mint, brown with chocolate,etc.)

27. SOLUTION Of ingredients WITH THE AID OF HEAT Used when it is desired to make syrup quickly and the ingredients are heat stable. After performing QC tests packed and distributed. BY AGITATION WITHOUT AID OF HEAT Used to avoid heat induced inversion of sucrose. It is more time consuming than previous method but product has max stability.

28. ADDITION OF SUCROSE TO A MEDICATED LIQUID OR FLAVORED LIQUID Generally Used for tinctures and fluid extracts. Most of them are prepared with alcoholic or hydro alcoholic vehicles. If alcohol soluble components are undesirable in corresponding syrup they are generally removed by: PERCOLATION OF EITHER SOURCE OF MEDICATING SUBSTANCE OR SUCROSE This method is used to form an extractive to which sucrose or syrup may be added. This method have two separate procedures :first the preparation of the extractive of the drug and then the preparation of the syrup. E.g. Ipecac syrup

29. Quality control tests for syrups Several tests are peformed , some of them are: Container Requirements The material of container should be inert. It should be closed tightly. If the included substances required protection from light, should be maintained in light resistant container e.g. Amber. During storage and use of syrup involves crystallization of sugar within the screw cap. This issue can be overcome by addition of polyhydric alcohols. Labelling Requirements Name of the product, List of active ingredients, Batch no assigned by manufacturer, Dosage, Expiry date, storage conditions, Direction for use, Warnings, Precautions, Name and address of the manufacturer.   Clean and purified vehicle (Distillation )   Sucrose concentration (Assay of Active ingredient) Viscosity  Refractive index  Visual inspection  Specific gravity  Ph measurement Optical rotation

30. Patient Counselling Pharmacist should counsel the patient about correct use of corresponding dosage form. Possible Side effects and interaction of the medication. Counsel the patient about storage conditions . MERITS DEMERITS Ability to mask the bad taste of drugs  Not suitable in emergency and for unconscious patient.   Can be self administered  Not convenient for a patient having some GIT disorders.  Viscous nature contributes to soothing effect on irritated throat tissues.  Contain little or no alcohol convenient for both pediatric and geriatric patient.  Provide a mean for extemporaneous preparation of medication.

31. MEDICATED SYRUP NON MEDICATED SYRUP SIMPLE SYRUP

32. ORAL REHYDRATING SOLUTION

33. ORAL REHYDRATING SOLUTION NAME OF PHARMACEUTICAL PRODUCT GENERAL PRODUCT INFORMATION : Oral rehydration solution (ORS) is an oral powder–containing mixture of glucose sodium chloride, potassium chloride, and sodium citrate. After being dissolved in the requisite volume of water they are intended for the prevention and treatment of dehydration due to diarrhea, including maintenance therapy. Low-osmolarity oral rehydration salts PHARMACEUTICAL FORM Oral powder. A white, crystalline powder; odorless QUALITATIVE AND QUANTITATIVE COMPOSITION COMPONENT CHEMICAL FORMULA CONCENTRATION Sodium chloride NaCl 2.6 Glucose anhydrous C6H12O6 13.5 Potassium chloride KCl 1.5 Trisodium citrate, dihydrate C6H5Na3O7,2H2O 2.9

34. APPEARANCE OF PRODUCT A white, crystalline powder, odorless APPEARANCE OF SOLUTION The solution should be clear and odorless, or should have only a faint yellow stain. PREPARATION OF ORS Formulations are available for reconstitution . Then add the specific amount of water required to prepare the powder forms. These products should not be mixed with or given with other electrolyte containing liquids such as milk or fruit juices. PREPARATION OF ORS AT HOME Six (6) level teaspoons of Sugar. Half (1/2) level teaspoon of Salt. One Litre of clean drinking or boiled water and then cooled - 5 cup fuls (each cup about 200 ml.) PACKAGING AND PRESENTATION ORS is a powder for dilution in 200 mL, 500 mL, and 1 L. Products are packed in hermetically sealed, laminated sachets. The sachets may be made of multi-ply laminations with aluminum foil or polyethylene foil. The multi-ply laminated aluminum foil sachet is usually recommended for ORS. A compound of polyethylene (inside), aluminum (middle), and polyester or any other suitable coating compound (outside) has proved to be a satisfactory combination for packing ORS. The packaging configurations for ORS procured by UNICEF are: – ORS low osmolarity, 20.5 g/1 L – ORS low osmolarity, 10.2 g/0.5 L

35. LABELLING ORS should be procured with packaging designated with: (1) the total net mass and the mass of the contents of each constituent, both expressed in grams; (2)the required volume of water to reconstitute the solution; (3 ) directions for the preparation of the solution and its administration; and (4) a warning that any solution that remains unused 24 hours after preparation is to be discarded.. STORAGE, TRANSPORTATION, AND DISTRIBUTION ORS is stable at room temperature and does not require cold chain storage ORS should be kept in a sealed packet; if a free-flowing powder is required, it should be kept in an airtight packet, preferably made of aluminum laminate. Discard any solution that remains unused 24 hours after preparation. PRODUCT SPECIFICATIONS The product must meet pharmacopoeia specifications, such as those of the International Pharmacopoeia, US Pharmacopoeia, and British Pharmacopoeia, depending on the quality assurance policy of the procurement agency or the equivalent thereof. STABILITY product stability also depends on these conditions: the raw material is dry, the sealing is perfect, and the final product is stored appropriately. ORS containing citrate (as opposed to bicarbonate containing ORS) is stable at ambient temperatures/humidity and is unlikely to undergo any significant degradation as a result of heat/humidity if it is properly manufactured, packaged, and sealed. Storage condition: ORS should be kept in a sealed packet; if a free-flowing powder is required, it should be kept in an airtight packet, preferably made of aluminum laminate. Discard any solution that remains unused 24 hours after preparation

36. PATIENT COUNSELLING RECOMMENDATION OF WHO AND UNICEF Pharmacists advised patients or guardians, where appropriate, on preparing ORS, on the treatment schedule and instructed on the required storage conditions. pharmacists would also advise on maintaining adequate nutritional intake DEGRADATION Shelf life: 2–3 years, depending on the manufacturer. It is recommended to check the product label before use. DOSAGE ORS and zinc are recommended by WHO for combination use to ensure the effective treatment of diarrhea; in order to improve compliance, a copackage of ORS and zinc in accordance with WHO treatment protocol guidelines is offered by some manufacturers to improve treatment regimen adherence. Age under 4 months 4 to 11 months 12 to 23 months 2 to 4 years 5 to 14 years 15 years and over Weight under 5 kg 5 to 7.9 kg 8 to 10.9 kg 11 to 15.9 kg 16 to 29.9 kg 30 kg and over ORS in ml 200 to 400 400 to 600 600 to 800 800 to 1200 1200 to 2200 2200 to 4000

37. METHOD OF ADMINISTRATION SPECIAL WARNINGS AND PRECAUTIONS FOR USE CLINICAL PARTICULARS THERAPEUTIC INDICATIONS ORS is indicated for the treatment of diarrhea and fluid loss due to diarrhea in infants, children, and adults. The amount of ORS solution needed for rehydration is calculated based on the child’s weight. The amount of solution required also depends on the child’s dehydration status. Children with more marked signs of dehydration or who continue to pass frequent watery stools will require more solution than those with less marked signs or who are not passing frequent stools. Administer with care in cases of acute dehydration, heat cramps, extensive tissue destruction, or if patients are receiving potassium-sparing diuretics. It is very important to dissolve ORS in water of the correct volume. A weak solution will not contain optimum glucose and electrolyte concentration and a strong solution may give rise to electrolyte imbalance. Diarrhea can have very serious consequences in children under 3 years old. Immediate medical advice should be sought. In other age groups, if symptoms persist for more than 24–48 hours, consult a doctor. Diarrhea can have very serious consequences in children under 3 years old. Immediate medical advice should be sought. In other age groups, if symptoms persist for more than 24–48 hours, consult a doctor. UNDESIRABLE EFFECTS The following adverse effects have been reported although more commonly following excessive amounts: hypernatremia, edema, nausea, vomiting, diarrhea, abdominal cramps, thirst, reduced salivation, lachrymation, sweating, fever, tachycardia, renal failure, respiratory arrest, headache, dizziness, restlessness, irritability, weakness, muscular twitching, coma, convulsions, hyperkalemia, gastrointestinal ulceration, metabolic alkalosis, muscle hypertonicity, flatulence, dehydration, and raised blood pressure

38. PACKING SPECIAL WARNINGS AND PRECAUTIONS FOR USE MANUFACTURING PROCESS ORS is a straightforward product to manufacture, but some specific procedures should be observed to ensure the quality of the product. Recommendations and technical procedures that should be considered during the manufacture of ORS include the following; After prolonged storage in hot and humid climates, the raw materials may have absorbed a substantial amount of moisture,and have a water content higher than the indicated limit of 1%. The use of such ingredients for the manufacture of ORS may result in accelerated decomposition. Therefore, if a raw material containing water in excess of the indicated limit is to be used, it is preferable to dry it at the recommended temperature as follows: glucose, anhydrous at max. 105°C; sodium chloride, potassium chloride, and trisodium citrate at max 130°C. The kind of packaging material to be used for ORS depends mainly on the required standard of stability, the climatic conditions, and the available resources.

39. COLONIC ORAL LAVAGE SOLUTION

40. ORAL COLONIC LAVAGE SOLUTION a colonic lavage solution presently used for gut cleansing in preparation for colonic procedures, can be an effective agent in the treatment of chronic constipation. Polyethylene glycol-electrolyte solution (PEG-ES) GENERAL PRODUCT INFORMATION : NAME OF PHARMACEUTICAL PRODUCT PHARMACEUTICAL FORM Oral powder, A white, crystalline powder QUALITATIVE AND QUANTITATIVE COMPOSITION COMPONENT CONCENTRATION PEG-3350 236.00 g Sodium sulfate 22.74 g Sodium bicarbonate 6.74 g Sodium chloride 5.86 g Potassium chloride 2.97 g

41. ORAL COLONIC LAVAGE SOLUTION a colonic lavage solution presently used for gut cleansing in preparation for colonic procedures, can be an effective agent in the treatment of chronic constipation. Polyethylene glycol-electrolyte solution (PEG-ES) GENERAL PRODUCT INFORMATION : NAME OF PHARMACEUTICAL PRODUCT PHARMACEUTICAL FORM Oral powder, A white, crystalline powder PREPARATION OF COLONIC LAVAGE SOLUTION You will need to mix your medication with lukewarm water so that it will be ready to drink. Read the directions that come with medication to see how much water should be added to the powder and whether to mix it in the container it came in or in another container. Shake or stir the mixture so that the medication is mixed evenly. If your medication comes with flavor packets, you may add the contents of one packet to the medication to improve the taste, but should not add any other flavorings to the medication. Do not mix medication with any liquid other than water, and do not try to swallow the medication powder without mixing it with water. After you mix your medication, you may chill it in the refrigerator to make it easier to drink. However, if giving the medication to an infant, you should not chill it.

42. Cleanses the bowel by induction of diarrhea. The osmotic activity of polyethylene glycol 3350, in combination with the electrolyte concentration, results in virtually no net absorption or excretion of ions or water. Accordingly, large volumes may be administered without significant changes in fluid and electrolyte balance. CLINICAL PHARMACOLOGY INDICATION AND USAGE ADMINISTRATION INSTRUCTIONS PRIOR TO DOSAGE It is indicated for bowel cleansing prior to colonoscopy or barium enema X-ray examination Traditionally, preparation of the bowel for procedures such as a colonoscopy consisted of administration of a clear liquid diet for 24 to 48 hours preceding the procedure, administration of an oral laxative such as magnesium citrate or bisacodyl the night before, and a cleansing enema administered 2 to 4 hours prior to the procedure. Consequently, an alternative method to prepare the gastrointestinal tract has been devised. This procedure requires less time and dietary restriction and obviates the cleansing enemas. This method entails oral administration of a balanced solution of electrolytes with polyethylene glycol (PEG-3350-Electrolyte Solution), i.e., PEG-ES. Before dispensing it to the patient, the pharmacist reconstitutes this powder with water, creating an iso-osmotic solution having a mildly salty taste. Ideally the patient should not have taken any food 3 to 4 hours before beginning to take the solution . In no case should solid foods be taken by the patient for at least 2 hours before the solution is administered INSTRUCTIONS AFTER DOSAGE No food except liquids are permitted after this product is administered and prior to the examination The product must be stored in the refrigerator after reconstitution, and this is somewhat in decreasing the salty taste 7 DAYS BEFORE 3 DAYS BEFORE 2 DAYS BEFORE 1 DAY BEFORE ON THE DAY take your medicines after talking to your doctor follow low residue diet begin your bowel prep drink clear liquids only don’t eat food continue your bowel prep finish your bowel prep don’t eat food don’t drink anything 4 hrs before your arrival time

43. The recommended adult dose of this product is 4L of solution before the gastrointestinal procedure. The patient is instructed to drink 240 ml of solution every 10 mins until about 4L is consumed. DOSAGE ADVERSE EFFECTS INFORMATION TO PATIENTS no solid food should be ingested during the 3 to 4 hour period prior to the initiation of colonic lavage solution with flavor pack administration The patient is advised to drink each portion quickly rather than sipping it continuously. CONTRAINDICATIONS Nausea, stomach pain, cramps, or fullness, bloating, rectal irritation, weakness, heartburn, thirst, hunger, Chills Gastrointestinal (GI) obstruction, ileus, or gastric retention • Bowel perforation • Toxic colitis or toxic megacolon • Known allergy or hypersensitivity to any component of solution PRECAUTIONS This product may contain inactive ingredients, which can cause allergic reactions or other problems tell your doctor or pharmacist your medical history, especially of: certain stomach/intestinal problems history of vomiting easily/often, heart problems not recommended when abdominal pain, nausea, or vomiting are present Unconscious or semiconscious patients should be observed during the administration of solution

44. WARNING PRINCIPAL DISPLAY PANEL No other additional ingredients (e.g., flavorings) should be added to the solution

45. STORAGE AND STABILITY Store the sachets and bottle at room temperature, between 15oC and 30oC. Once reconstituted, the solution should be used within 48 hours after mixing if stored at room temperature. If kept refrigerated (between 2oC and 8°C), use within 30 days. Discard unused Portion

46. GARGLES & MOUTH WASHES

47. GARGLES & MOUTH WASHES: GARGLES and MOUTHWASH both are used for different purpose. Gargle which is used to treat infections in the throat. Mouthwash is used for cleaning and de-odor the oral cavity. TYPES OF MOUTH WASHES: THERAPEUTIC MOUTHWASHES: COSMETIC MOUTHWASHES Serve clinical purposes, like attacking bacteria and plaque, or strengthening teeth with fluoride & to reduce plaque, gingivitis, dental caries, and stomatitis . A word of caution:  overuse of an antiseptic mouthwash may cause tooth discoloration. Serve only to mask bad breath and leave your mouth with a pleasant taste – like a mint but doesn’t really do much against fighting decay, strengthening tooth enamel, or protecting teeth.   A word of caution:  mouthwash that contains alcohol may dry out the mouth and cause more dental problems. “Gargles & Mouthwashes are aqueous solutions that are intended for treatment of the throat and are generally formulated in a concentrated form.”

48. OTHER TYPES OF MOUTH WASHES: These are free of fluoride and alcohol. The most common natural mouthwash comes in the form of warm water and salt. This concoction can reduce inflammation, ease gum bleeding, and fight against bacteria. A word of caution:   don’t swallow the saltwater, just swish. Fight against bacteria and prevent the buildup of plaque and gum diseases. NATURAL MOUTHWASH FLUORIDE MOUTHWASH TOTAL CARE MOUTHWASH: Fluoride mouthwash contains sodium fluoride, which is use to help build strong teeth and protect enamel from decay.  fluoride mouthwash is not recommended for children under six. A word of caution:  mouthwash that contains alcohol may dry out the mouth and cause more dental problems.

49.   ACTIVE INGREGIENTS: PROPERTIES 1 Alcohol As a co-solvent may act to enhance the antimicrobial properties of the therapeutic agent. 2 Chlorhexidine As an antiseptic to control plaque & gingivitis. 3 Fluoride Fights tooth decay and strengthens enamel. 4 Cetylpyridinium Chloride Eliminates bad breath and kills bacteria. 5 Hydrogen peroxide Whitens teeth. 6 Essential oils Antifungal and Antibacterial properties 7 Sodium Chloride Retard growth of microorganisms. 8 Sodium Bicarbonate Disinfectant and Antiseptic properties. 9 Sodium Lauryl Sulphate ( sls ) Anti- palque activity. FORMULATION

50. INDICATIONS TOPICAL PAIN RELIEF ALVEOLAR OSTEITIS (DRY SOCKET). TOOTH DECAY PLAQUE AND GINGIVITIS WHITENING ORAL MALODOR DIAGNOSTIC PURPOSE XEROSTOMIA

51. Container:Amber fluted medical bottle(50 mL , 100 mL , 200 mL ) LABEL COMPOUNDIND AND DISPENSING

52. LINCTUSES

53. “Linctuses are viscous, monophasic liquid preparation containing a high concentration of syrup intended to sipped and swallowed slowly for treatment of cough.” Linctuses may also be formulated as sugar-free alternatives in which sucrose is replaced by sorbitol and the required concentration of sweetening agent. Prepared by Monophasic Liquid Preparation Method. The usual dose of linctuses is 5.0 ml. PREPARATION DOSE LINCTUSES

54. Vehicles: Syrup, ( Tolu syrup), glycerin, sorbitol . Adjuncts: Used to improve Safety, efficacy and palatability. Chemical Stabilizer: Mostly stable because of syrup. Preservative: High concentration of syrup acting as preservative. Tolu syrup has antibacterial action due to benzoic acid and cinnamic acid present in it.Benzoic acid in codeine phosphate linctuses. Coloring Agent: Coal tar dyes. Flavoring agent:black current syrup, lemon syrup, oxymel and benzaldehyde etc Demulcent. Sedative. Expectorant action. COMPOSITION INDICATIONS

55. Linctuses are supplied in well closed air tight container having screw cap stored in a cool place, protected from light. COMPOUNDIND AND DISPENSING LABEL

56. REFERENCES: Pharmaceutical compounding and dispensing Essential pharmaceutics Aulton pharmaceutics 5th Edition Ansels pharmaceutical dosage forms and drug delivery system 9th Edition Remington(The science and practice of pharmacy ) 21 st Edition BOOKS: WEBSITES: https://www.webmd.com/drugs/2/drug-63819/elixir-oral/details http://www.uobabylon.edu.iq/eprints/publication_3_31959_6264.pdf http://pharmacy.uobasrah.edu.iq/images/stage_three/Pharmaceutical_Technology_I/3%20Elixirs.pdf https://www.rxlist.com/colyte-drug.htm#medguide https://www.pharmacompass.com/active-pharmaceutical-ingredients/golytely https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a8b15625-ca7c-4d57-9f36-3ac2a6d13665&type=display

57. https://journals.lww.com/ajg/Fulltext/2009/10003/Off_label_Use_of_Polyethylene_Glycol_3350.496.aspx https://europepmc.org/article/med/2178398 https://medicalguidelines.msf.org/viewport/EssDr/english/oral-rehydration-salts-ors-16684387.html https://www.webmd.com/drugs/2/drug-13607/colyte-oral/details https://www.medlife.com/blog/world-ors-day-special-benefits-preparation/ https://medlineplus.gov/druginfo/meds/a601097.html#how https://www.drugs.com/cons/oral-rehydration-salts.html https://www.ndrugs.com/?s=colonic%20lavage%20solution Preventive Dentistry - Wexford Dental - Different Types of Mouthwash - Dr. Chad Scott (paragondentalpgh.com) https://www.academia.edu/36403285/Fasttrack_Pharmaceutics_Dosage_Form_and_Design_pdf Microsoft Word - DentifricesandMouthwashesIngredientsandtheir use20031.doc ( uio.no ) 6.2.1.2.Liquid-preparations-for-oral-use.pdf (who.int) Linctuses is a form of Liquid Dosage, prepared using Monophasic Liquid Preparation Method (preservearticles.com) http://flexiblelearning.auckland.ac.nz/pharmacy101/9/files/compounding_lecture_2012_for_cecil.pdf WEBSITES: