unit 3. liquid (monophasic) dosage forms.pptx

Liquid dosage forms are medications that are administered in a liquid state. They are a popular option for patients who have difficulty swallowing pills or capsules, or for medications that need to be absorbed quickly into the body.

There are several different types of liquid dosage forms, each with its own advantages and disadvantages. Here are some of the most common types:

Solutions: Solutions are homogeneous mixtures in which a solid, liquid, or gas (the solute) is dissolved in a liquid (the solvent). In pharmaceutical terms, solutions are clear, single-phase liquids containing a dissolved drug and other inactive ingredients such as flavorings, sweeteners, and preservatives.
Liquid dosage forms Solutions

Suspensions: Suspensions are heterogeneous mixtures in which solid particles (the solute) are dispersed throughout a liquid (the solvent). Unlike a solution, the particles in a suspension are not dissolved and will settle out over time if not shaken well before use. Suspensions are often used for medications that are not soluble in water.
Liquid dosage forms Suspensions

Elixirs: Elixirs are clear, sweetened hydroalcoholic solutions that are often flavored to disguise the taste of the medication. They are similar to syrups, but contain a lower concentration of sugar. Elixirs are often used for children or adults who have difficulty swallowing pills.
Liquid dosage forms Elixirs

Syrups: Syrups are concentrated, viscous solutions that contain a high concentration of sugar. The sugar helps to preserve the medication and also makes it more palatable. Syrups are often used for children or adults who have difficulty swallowing pills.
Liquid dosage forms Syrups

Liniments: Liniments are viscous, opaque liquids used for topical application to the skin. They are used to soothe pain and inflammation.
Liquid dosage forms Liniments

Lotions: Lotions are shakable liquid preparations for topical application to the skin. They are used to soothe and protect the skin. Lotions can also be used to deliver medication through the skin.
Liquid dosage forms Lotions

Liquid dosage forms offer a number of advantages over other dosage forms, such as:

Easier to swallow than pills or capsules
More rapid absorption into the body
Can be more easily adjusted for different dosages
Can be flavored to make them more palatable
However, there are also some disadvantages to liquid dosage forms, such as:

Shorter shelf life than solid dosage forms
Can be more difficult to measure accurately
May require refrigeration
Can be bulky and difficult to carry.

1. Liquid Dosage Forms Ms. Akanksha Patel M.Pharm (Pharmaceutics) Asst prof.

2. Introduction- Liquid dosage forms are the solutions of medicaments that are used to induce therapeutic effects, internally and externally.  . There are potential advantages of oral liquid dosage forms, such as no dissolution time and rapid absorption from the stomach/intestine compared to tablets, which may be an important factor for pain-relieving drugs .

3. Classification Monophasic- containing only one base phase Biphasic- containing two base phase

4. Advantages- Faster absorption than solids. Palatable pleasant to taste. Best choice for children and old persons. Easy to swallow. Simple and fast to formulate It can be administered by various routes : Oral , Parenteral (injection),enema for rectal use, nasal, otic (ear ), and ophthalmic preparation . Disadvantages- Has Short half-life due to low stability. Has less accuracy. Need special storage and transferring conditions. Is easily infected by microorganisms. Has special storage requirements. They are bulky, so difficult to transport and store . Other major sign of drug instability are color change, Precipitation, microbial growth etc. When expose to direct sunlight it may undergo hydrolysis, so need to store in cool and dark place.

5. EXCIPIENTS USED IN LDF 1. Vehicles/ Solvents In liquid pharmaceutical formulations, vehicles are major components used as a base in which drugs and other excipients are dissolved or dispersed . They function by breaking of bond and reducing effective charge on ions thus, increasing solute-solvent forces of attraction which are eventually greater than solute-solute and solvent-solvent forces of attraction. Vehicles used in the formulation of liquid dosage forms may be aqueous (e.g., water, polyhydric alcohols, hydro-alcoholic solutions and buffers) or oily (e.g., vegetable or mineral oils, organic oily bases, emulsified bases etc ). The choice of vehicle used depends on the nature and physicochemical properties of the active pharmaceutical ingredient (API) and the intended use of the formulation . 2. Co-solvents Co-solvents are primarily liquid components often used to increase the water solubility of drugs . Its solubility can not be increased by pH adjustment. They work by reducing the interfacial tension between predominantly aqueous solutions and hydrophobic solutes. Examples: glycerol, propylene glycol, ethanol, the low molecular weight PEGs etc.

6. 3. SURFACTANTS- SURFACTANTS OR SURFACE-ACTIVE AGENTS ARE MOLECULES WITH WELL-DEFINED POLAR (HYDROPHILIC) AND NON-POLAR (HYDROPHOBIC) REGIONS THAT ASSOCIATE IN AQUEOUS MEDIA TO FORM DYNAMIC AGGREGATES, KNOWN AS MICELLES. DEPENDING ON THE NATURE OF THE POLAR AREA, SURFACTANTS CAN BE ANIONIC (E.G., SODIUM DODECYL SULFATE), CATIONIC (E.G., TRIALKYLAMMONIUM), ZWITTERIONIC (E.G., GLYCINE AND PROTEINS) AND NONIONIC (E.G., POLYETHYLENE GLYCOL). 4 . preservatives Preservatives Are Chemical Compounds That Are Added To Formulations To Protect Them From Microbial Contamination During Production And Over Storage Time. An Ideal Preservative Should Be Effective At Low Concentrations Against All Possible Microorganisms, Non-toxic, Non-sensitizing, Soluble And Compatible With The Api , Other Excipients, And The Container System, Stable For The Shelf-life Of The Product. 5. Drug Drug Api A Substance Which Has A Therapeutic Effect When Administered. Drug Is Not Administered As It Is.

7. 6. Viscosity modifiers/ Suspending agents The excipients that minimize interparticle attraction and aggregation by functioning as energy barrier thus retarding particle settling. The factors considered in the selection of the appropriate suspending or viscosity enhancing agents include; desired rheological property, suspending ability in the system, pH stability, chemical compatibility with drug substance and other excipients, reproducibility, hydration time, and cost. Common viscosity modifiers example s; cellulose derivatives (e.g., methylcellulose, microcrystalline cellulose, carboxymethylcellulose , ethylcellulose , hydroxyethylcellulose , hydroxypropyl cellulose and hydroxypropyl methylcellulose etc ), clays (e.g., hectorite , bentonite, aluminium and/or magnesium silicate), natural gums (e.g., acacia, guar gum, tragacanth , xanthan gum, alginates, carrageenan and locust bean gum), synthetic polymers (e.g., carbomers , polyvinyl pyrrolidone , polyvinyl alcohol and poloxamer ), miscellaneous compounds (e.g., colloidal silicon dioxide and silicates).

8. 7. Colouring agents : Colouring agents To give aesthetic appeal and impart pleasing appearance. Mask discoloured , degraded ingredients and to maintain appearance during shelp life. For identification. Synthetic colours, Natural Colours ,: Erythrosin,Tartrazine , Blue , Vegetable colours: Chlorophyll, carotene. Animal colour: Cochineal. Mineral Colours: Titanium dioxide, ferric oxides. 8. Flavouring agents : Flavouring agents To mask unpleasant smell. Vitamins with cherry, Strawbery or raspberry navour . Paediatric drops fruity flavour . Volatile oils including cinnamon, clove, lemon, orange and peppermint flavour which activate olfactory cells. Natural Sources: Pine-apple, Cardamom, ginger. Volatile oils- Clove, lemon, orange, rose. Synthetic Chemicals: Alcohol, aldehydes , fatty acids, esters. 9. Sweetening agents: Sweetening agents Are natural or synthetic agents. Sugars : PolyhydrW ' alcohols: Artificial : 14 Sucmse , fructose, glucose, syrup. Sorbitol, Mannitol, glycerin . Saccharin, Aspartame . 10. Buffers : Buffers can Resists any change in pH when acid or base is added. To encounter stability problem. pH -7.4 to 8.4. Eg . Monobasic sod. Acetate, sod. Citrate, pot. Phosphate , pot. MetaphosphatesThese are materials which when dissolved in a solvent will enable the solution to resist any in pH. Pharmaceutical buffers are carbonates, citrates, g luconates , la ctates , phosphates or tartrates. As the pH Of body fluid is 7.4, products such as injections, eye drops and nasal dropsshou½ be buffered at this to avoid irritation .

9. Excipients Role Examples Solvents/ vehicles Liquid in which drugs and other excipients are dissolved or dispersed. Purified water, alcohol, acetic acid, acetone, vegetable or mineral oils, organic oily bases, emulsified bases etc. Co-solvents Enhance solubility of drug substance in the vehicle Ethanol. glycerol, propylene glycol etc Surfactant Enhance solubility of drug substance in the vehicle Cetrimide , sodium lauryl sulphate, triethanolamine Preservatives Prevents microbial growth in the formulation Parabens, phenylmercuric nitrate, sodium benzoate, benzalkonium chloride Buffers Regulate the pH of the formulation Phosphate buffers, Acetate buffers, Citric acid Phosphate buffers etc Antioxidants Control oxidation Sodium bisulphite, ascorbic acid, butylated hydroxytoluene etc Thickening agents. Prevent settling/sedimentation, modify viscosity. Methylcellulose, Hydroxyethylcellulose , Microcrystalline cellulose etc. Sweeteners Enhance the palatability of oral liquid formulations Sucrose, saccharin, aspartame, sorbitol Flavouring agents Enhance the palatability of oral liquid formulations Lemon oil, orange oil, peppermint, menthol Colourants Enhance the aesthetic appearance of the formulation Amaranth, Erythrosin, Eosin, Tartarazine etc. Antifoaming agents Discourage formation of stable foam Simethicone, Organic phosphates, Alcohols, Paraffin oils, Sterates and glycols. Humectants Retard evaporation of aqueous vehicles from dosage forms Propylene glycols, Glycerol, Polyethylene glycol etc. Emulsifying agents Prevent coalescence of the dispersed globules Sodium Lauryl Sulphate, Cetrimide , Macrogol esters, Sorbitan esters etc. Flocculating agents Prevent caking Starch, Sodium alginate, Carbomer.etc . Excipient used in aerosol Propellant Developing pressure in container which expels the product Trichloromonofluoromethane , Dichlorodifluoromethane, etc.

10. Solubility enhancement techniques- Precipitation technique. Hot melt method. Particle size reduction. Solvent evaporation method. pH adjustment.

11. Monophasic Monophasic liquid dosage forms are liquid preparations containing only one base. These are also known as true solutions . A true solution is a clear homogenous mixture, prepared by dissolving a solid, liquid, or gas in a liquid phase. Monophasic liquid dosage forms are made for internal as well as external use. Syrups, mixtures, elixirs, and linctuses are meant for internal use, while gargles, mouthwashes, lotions, liniments, eye drops, ear drops, nasal drops, douches, and throat pains are meant for external use . Liquid for internal use: The largest proportion of the liquid formulations are liquid for internal use. Drug should have sufficient solubility in commonly used solvent, like water.

12. Syrups Syrups are concentrated aqueous solutions containing one or more sugar components, chiefly sucrose, or sugar substitute. The concentration of sugar in syrup is 66.7 % W/W. Syrups may be medicated or nonmedicated . The nonmedicated often referred to as simple syrups are used as vehicles for medicinal substances to be added later, either in the extemporaneous compounding of prescriptions or in the preparation . These dosage forms are generally used for children and old-age-conscious persons. For example Benadryl syrup. Preparation of Syrups: Syrups are prepared by any of the following four general methods, Solution with the aid of heat : Sugar is added to the purified water and heated until it dissolves. Then, the other required heat-stable components are added to the hot syrup, the mixture is cooled and its volume is adjusted by the addition of purified water. The use of heat facilitates the rapid solubility of the sugar and other components of syrups. Solution by agitation without heat: Sucrose and other ingredients are dissolved in purified water by placing the ingredients in a vessel of greater capacity than the volume of syrup to be prepared, the permitting thorough agitation of the mixture . Addition of sucrose to a medicated liquid or to a flavored liquid: Medicated liquid such as tincture or fluid extract is employed as the active ingredient in the preparation of syrup. If the extract contain alcohol-soluble ingredients and the amount of alcohol is high, then sucrose is added directly and stirred. If the alcohol content is low and all the ingredients are water soluble, then the liquid extract directly mixed with the prepared syrup . Preparation of syrup by percolation: Purified water or an aqueous solution is added slowly to a bed of crystalline sucrose, thereby dissolving it and forming the syrup. If needed, a portion of the percolate recycled.

13. Elixirs Elixirs are clear, sweetened hydroalcoholic solutions. They usually contain alcohol (10%-40 %) and are used to solubilize lipophilic (fat-soluble) active ingredients. Examples like; Some Antihistaminics , antibiotics, sedatives drugs that are manufactured as elixirs . Compared to syrups, elixirs are usually less sweet and less viscous because they contain a lesser amount of sugar. Because of their hydroalcoholic character, elixirs are better able than are syrups to maintain both water-soluble and alcohol-soluble components in solution . Elixirs are of two types as follows: 1 . Non-medicated elixir : These are used as diluting agents or solvents for drugs containing approximately 25% alcohol. 2 . Medicated elixirs : Elixirs containing therapeutically active compounds are known as medicated elixirs, for example, phenobarbital elixir USP, dexamethasone elixir USP . Example; Piperazine citrate elixir Piperazine citrate 18 g Chloroform spirit 0.5 ml Glycerin 10 ml Orange oil 0.025 ml Syrup 50 ml Purified water ( q.s .) 100 ml Procedure- Piperazine citrate is dissolved in a part of purified water. Orange oil, glycerin , syrup, chloroform spirit and sufficient quantity of water are added to produce the required volume. The resulting solution is mixed well and filtered if needed.

14. Draught A draught is an older term used to describe liquid oral preparations which contain only one or two large doses. The volume of the formulation is usually larger than that generally utilised in traditional mixture formulations and each dose is supplied in separate bottles.

15. Linctus Linctuses are viscous liquid oral preparations that are prescribed for relief of cough . They contain medicaments that have demulcent or expectorant action. Linctuses should be taken in small doses, sipped and swallowed slowly without diluting with water to have the maximum and prolonged effect of medicament. Formulation of linctuses requires the following : 1 . Vehicles: Simple syrup is commonly used as the vehicle. Syrup tolu is preferred in certain cases because of its aromatic odor , flavor . Moreover, it is believed to have a mild expectorant action . 2 . Adjuvants: Commonly used as follows : ( a) Chemical stabilizers: The stability of linctuses is due to the presence of the simple syrup as vehicle . ( b) Coloring agents: Coal tar dyes. (c ) Flavoring agents: Lemon syrup, black current syrup, oxymel . (d ) Preservatives: Syrup has high osmotic pressure, which eliminates additional use of other preservatives . Example; Codeine linctus BPC Codeine phosphate 0.3 g Lemon syrup 20 ml Benzoic acid solution 2 ml Chloroform spirit 2 ml Compound tartrazine solution 1 ml Purified water 2 ml Syrup ( q.s .) 100 ml Method; Codeine phosphate is dissolved in water. To this, benzoic acid solution, chloroform spirit and compound tartrazine solution are added and mixed well. Then, lemon syrup is added and the volume is made up with syrup.

16. Gargles Gargles are aqueous solutions used to prevent or treat throat infections . They are usually available in concentrated form with direction for ‘ dilution with warm water before use ’. They are brought into intimate contact with the mucous membrane of the throat and are allowed to remain in contact with it for a few seconds, before they are thrown out of the mouth, They are used to relieve soreness in mild throat infection. Phenol or thymol is generally present in small concentration for its antibacterial activity . Potassium chlorate is also included in gargles for its weak astringent effect to tone up a relaxed throat. It also stimulates secretion of saliva which relieves dryness. Example ; Prepare and dispense 100 ml of Potassium chlorate Monophasic liquid dosage forms potassium chlorate and phenol gargles Potassium chlorate 30g Patent blue V 0.009g Liquid phenol 15ml Water 1000ml Method: Dissolve the potassium chlorate in warm water. Cool and add liquefied phenol. Add the dye solution, filter and make up the volume. Transfer to a container, cork, label and dispense.

17. Throat paints Throat Paints Throat paints are viscous liquid preparations containing one or more medicaments and are used for mouth and throat infections such as pharyngitis , laryngitis, tonsillitis . They are highly viscous due to their high content of glycerin . They are made viscous, so that the drug would remain in contact with the mucus membrane for a longer time period. They should be stored in coloured fluted airtight containers. Labelling as- " For external use only" and "Apply with brush .“ The formulation contains; vehicles , flavouring agents, colouring agents and sweetening agents. Medicaments such as antiseptics, astringents and anti- infectives are commonly incorporated in throat paints . Example; Mandl's paint Iodine 1.25 g Potassium iodide 2.5 g Purified water 2.5 ml Peppermint oil 0.42 ml Alcohol (95 %) 3.75 ml Glycerin ( q.s .) 100 ml Method; Potassium iodide and iodine are dissolved in purified water using a glass mortar and pestle with a small portion of glycerin . To this, peppermint oil dissolved in alcohol is added and mixed and then sufficient glycerin is added to produce the required volume.

18. Mouthwashes Mouthwashes are aqueous solutions having a pleasant taste and odour to clean and deodorize the buccal cavity. They are often used for dental hygiene , but an antibacterial mouthwash can also be used to treat gum infections . The formulation of mouthwashes includes antibacterial agents, sweeteners, flavoring agents, alcohol, glycerine, and colouring agents . Containers Mouthwashes are dispensed in white fluted bottles . The label should clearly indicate the proper directions for ‘ diluting the mouthwash before use’ . Also apply the secondary label, " For external use only ". Example ; Prepare and dispense 50.0 ml of compound sodium chloride, mouth wash, compound sodium chloride mouth wash. Sodium bicarbonate 15g Sodium chloride 10g Peppermint water 1000ml Method: Dissolve the weighed quantity of sodium chloride and sodium bicarbonate in 3/4th of the peppermint water. Add more of peppermint water to produce the required volume. Transfer to a bottle, label and dispense.

19. Lotions Lotions are solutions, but may also be suspensions or emulsions, intended for external application to the skin. They are rubbed on the skin without friction with the help of some absorbent material such as cotton, wool or gauze soaked in it. These are applied directly to the skin for cooling and protective purposes. They are also used for their anti-septic actions, for example, calamine lotions, salicylic acid lotion. Labelling The containers should be labelled " For external use only” Sometimes on long standing lotion have a tendency to separate out Therefore, the container must be labelled " Shake well before use ". Example: Prepare and dispense 100 ml of calamine lotion L.P. Calamine150 g Zinc oxide 50 g Bentonite 30 g Sodium citrate 5g Liquefied phenol 5 ml Glycerin 50 ml Rose water upto1000 ml Method: Dissolve sodium citrate in rose water. Triturate the calamine, zinc oxide and bentonite with a solution of sodium citrate. Add the liquefied phenol. Add the glycerin . Add purified water in sufficient quantity to produce the required volume. Transfer the lotion to a bottle, cork, label and dispense.

20. Liniments Liniments are liquid preparation intended to be rubbed with friction and massaged onto unbroken skin to obtain analgesic, rubefacient or generally stimulating effects. They are usually solutions of oils, alcohols or soaps, but may be formulated as emulsions . Labelling The label must state, " for external use only " and " Shake the bottle well before use ". The label should carry the warning, " Not to be applied to open wound or broken skin ". Storage Liniment should be stored in tightly closed airtight containers in a cool place . Example; Prepare and dispense 1000 ml of turpentine liniment. Soft soap 90g Camphor 50g Turpentine oil 650ml Purified water, upto 1000ml Method: Mix the soft soap with small quantity of purified water. Prepare a solution of the camphor in the freshly rectified turpentine oil. Gradually add the camphor solution to the soap mixture with trituration till a thick creamy emulsion is formed. Add sufficient purified water to produce the required volume. Mix it thoroughly. Transfer the preparation to a bottle, label and dispense.

21. Eye drops Eye Drops Eye drops are sterile aqueous or oily solutions or suspensions that are used for instillation into the eye. They are applied into the cul-de-sac, the space between the eyeball and eyelid. It should be isotonic with lachrymal secretions, buffered and free from foreign particles to avoid irritation to the eye . Eye drops are sterilized by any one of the sterilization methods such as autoclaving, heating at 98°C-100°C for 30 minutes or filtration through 0.22 mm membrane filter. Eye drops are dispensed in neutral glass containers. Eye drops should be labeled " For external use only " Example ; Sodium chloride eye solution Sodium chloride 9 g Purified water ( q.s .)1000 ml Method; This is a simple solution prepared by dissolving sodium chloride in purified water filtered and sterilized. This is also called as normal saline solution .

22. Ear drops These are medicated solutions of drugs that are instilled in to the ear with a dropper. These are generally used for cleaning the ear, softening the wax and for treating the mild infections . However , this may cause inconvenience to patients because they have to lie down or tilt their head at angle of 45° when ear drops are administered. The commonly used medicaments in ear drops include anti- infectives , wax softener, antiseptics, astringents and anti-inflammatory agents . Example; Sodium bicarbonate ear drops BP Sodium bicarbonate 5 g Glycerin 30 ml Purified water ( q.s .) 100 ml Method ; Sodium bicarbonate is dissolved in water. To this, glycerin is added and mixed well. Glycerin provides the softening capacity to the solution and it reduces itching due to its emollient property. To this solution , the remaining quantity of water is added and the required volume is made up.

23. Nasal drops These are aqueous solutions that are instilled into the nose with a dropper. Nasal drops should be isotonic, having neutral pH and viscosity similar to nasal secretions. Use of oily vehicle is restricted because it inhibits the movement of cilia in the nasal mucosa and if used for long periods, it reaches the lungs and causes lipoidal pneumonia. The drops are used to reduce the swelling of nasal mucosa and the underlying tissues. Nasal drops are dispensed in coloured fluted bottles fitted with a dropper or in a suitable plastic container. The label should bear the indication " For external use only .“ Formulation of nasal drops requires vehicles such as purified water and liquid paraffin, tonicity-adjusting materials such as sodium chloride and dextrose, preservatives such as chlorobutanol and benzalkonium chloride and buffers such as phosphate buffer. Commonly incorporated medicaments in nasal drops include sympathomimetic, anti-inflammatory agents, adrenergic agents and decongestant. Example ; Ephedrine nasal drops BPC Ephedrine hydrochloride 9.14 g Chlorobutanol 4.5 g Sodium chloride 4.5 g Purified water ( q.s .) 1000 ml Method - Chlorobutanol is dissolved in sufficient quantity of purified water. Ephedrine hydrochloride and sodium chloride are dissolved in purified water in a separate container. These two solutions are mixed together and the final volume is adjusted with purified water to make up the required volume.

24. Enemas Enemas are solutions intended for introduction into the rectum or colon to cause evacuation of bowel or to bring about local or systemic effects. They are used for diagnostic purpose, especially for X-ray examination of bowel. They are suitable for drugs that cannot be given through oral or parenteral route. Classification: 1 . Cleansing or evacuating enema, for example, saline solution 2 . Carminative enema, for example, milk, olive oil 3 . Retention enema, for example, paraldehyde, starch and water 4 . Lubricating enema, for example, vegetable and mineral oil 5 . Medicated enema, for example, sodium phosphate, decussate sodium Enemas are dispensed usually in volume of 1000 ml in coloured fluted glass bottles, which should bear the labels "For external use only," "Lubricate the nozzle before administration," and "Warm the solution to body temperature," "For external use". Example ; Glycerine enema Glycerine 50ml Purified water 100 ml Method: As glycerine is miscible with water, it gets mixed well and forms a homogeneous solution. Glycerine stimulates the rectal mucosa, promotes defecation and lubricates and softens faecal material.

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