Monophasic Liquid Therapeutics Notes PDF

# Monophasic Liquids ## Unit III *Monophasic dosage forms are those liquid preparations in which there is only one phase and represented by a true solution.* *A true solution is a clear, homogenous mixture which is prepared by dissolving a solid, liquid or gas (solute) in a suitable solvent.* ##...

# Monophasic Liquids ## Unit III *Monophasic dosage forms are those liquid preparations in which there is only one phase and represented by a true solution.* *A true solution is a clear, homogenous mixture which is prepared by dissolving a solid, liquid or gas (solute) in a suitable solvent.* ## Advantages * Easier to swallow for children, old age, unconscious people. * Faster absorption since no need of dissolution. * Faster action than solid dosage forms * Can be administered via a number of routes like Oral, parenteral, topical, otic, nasal and ophthalmic preparations. ## Disadvantages * Bulky to carry. * Prone to microbial growth because contain water so they require preservative. * Solution can undergo hydrolysis when kept in direct sunlight. ## Classification ### Liquid meant for internal administration * Syrup * Mixture * Elixirs * Linctuses ### Monophasic Liquid dosage forms ### Liquid meant for external administration * Liquid applied to skin * Lotions * Liniments * Colloidions * Paints * Liquid used in mouth * Gargles * Mouthwashes * Throat paints * Liquid installed into body cavities * Douches * Ear drops * Nasal drops * Eye drops * Enemas ## Gargles * Gargles are aqueous and hydro alcoholic solution, which is used to treat or prevent throat infection. * They are dispensed in concentrated form with directions for dilution with warm water. * They are brought into intimate contact with mucous membrane of the throat and allow to remain for few moments. * They are used for deodorising and antibacterial effect. * It also stimulates secretion of saliva which relieves dryness, eg+ phenol gargles, potassium chloride, and pharet * Storage: Store at room temperature, store away from direct sunlight, heat and moisture. * Label: Should be labelled "for external use only". * Method of preparation: Dissolve the drug (eg, potassium chlorate) in warm water, cool and add liquified phenol. Add the dye solution, filter and make up volume. Transfer to a container, cork, label and dispense. ## Mouthwashes * A mouthwash is an aqueous solution which is most often used for its deodorant, refreshing or antiseptic effect. * It may contain alcohol, glycerin, synthetic sweeteners, surface-active agents, flavouring and coloring agents. * They mainly contain following substances - * Antibacterial agents: alkaline phinol, thymol glycerin etc. * Astringents: eg= Zinc sulphate, Znd etc. * Container: Narrow mouthed screw capped bottle * Label: Label on container should state - "Not to be swallowed in large amount" and store in cool and dark place. * Example: Prepare and dispense Compound Sodium chloride mouthwash. * Rx * Sodium bicarbonate → 10g * Sodium chloride → 15g * Concentrated peppermint emulsion → 25g * Purified water (q's). → 1000 ml * Double Strength chlorofarm water → 500ml * Method: Dissolve Sodium bicarbonate and sodium chloride in purified water, add concentrated peppermint emulsion and mise. Add double strength chloroform water. Finally makeup the volume with purified water. ## Throat Paints * Throat paints are viscous liquid preparations used for mouth and throat infections. Glycerin is commonly used as a base because being viscous, it adheres to mucous membrane for a long period. * Paints are solutions or dispersions of one or more medicament intended for application to the skin or in some cases to the mucous membrane. * They may contain volatile solvent that evaporates quickly to leaves a film of medicament. Due to high content of glycerin, paint adhere to the affected site and prolong the action of the medicament. * Storage: Paint Should be kept in airtight container. * Label: It should State "for external use only" Away from sunlight. * Example: Prepare and dispense Crystal Violet paints. * Rx * Crystal Violet → 1 gm. * Purified water → 1000ml (q.s). * Method of preparation: Disperse the Crystal Violet in 100ml of water and allow it to stand for one hour then filter, and now makeup the volume with water to 1000ml. ## Ear Drops * Ear drops are the liquid preparations in which the drugs are dissolved or suspended in a suitable vehicle like water, dilute alcohol, glycerin or any other suitable solvent and are intended for installation into the ear with a dropper. * Ear drops are generally used for cleansing the ear, drying weeping surfaces, softening the wax and for treating the mild infections. * Ear drops preparations are supplied in multi-dose or single-dose containers provided, if necessary, with a suitable administration device which may be designed to avoid the introduction of contaminations. *Example: Prepare and dispense 100ml of sodium bicarbonate ear drop. * Rx * Sodium bicarbonate → 5g * Glycerin → 30ml * Water (q's) → 100 ml. * Method of Preparation: Dissolve the sodium bicarbonate in water add glycerin and mix it well. Finally make up the volume with water, filter and transfer it to the container- *Use: It is used to relieve itching in the ear and soften the wax * Storage: The preparation are stored in a sterile, airtight, tamper - proof container * Labelling: The label Should State: * i) The name of any added antimicrobial/ preservative. * ii) For multidose container, the period after opening the container does not exceed 4 weeks, Unless otherwise specified in pharmacopoeia. ## Nasal Drops * Nasal drops are usually aqueous solutions intended for instillation into the nostrils by means of a dropper. They are commonly used for their antiseptic, local analgesic property. * It is considered as one of the major route of drug administration to achieve faster and greater bioavailability of drug, as the nasal mucosa has high permeation of drugs. * They are usually isotonic and slightly buffered to maintain a pH of 5.5 to 6.5. eg- atriicine adult Nasal drop 10ml. ### Advantages * High permeability of nasal mucosa compared with epithelial tissue of GIT. * Rapid onset of action. * No first pass metabolism. * Potential for direct delivery to CNS. * Higher bioavailability of drugs than that of GIT. ### Disadvantages * Sterility and stability problem. * Design of the device is difficult. * Difficult to use by pediatric and geriatric patients: * Example: Prepare and dispense 100ml of ephedrine nasal drops BPC. * Rx * Ephedrine hydrochloride → 0.5gm * Chlorobutol → 0.5gm * Sodium chloride → 0.5gm * Water (q's) → 1000 ml. * Method of Preparation: Dissolve the ephedrine hydrochloride, chlorobutol and sodium chloride in water, heat it, cool and filter, then make up the volume with water. Now, transfer it in suitable container, label and dispense it. ## Enema * Enemas are aqueous or oily solution or suspension or oil in water emulsion introduced into rectum or colon for cleansing (evacuation of feces), anthelmintic, anti-inflammatory or nutritive effect. * They may also be used for x-ray examination of the lower bowel. Among the commonly used drugs in solution form, which act as cleansing enemas include isotonic solution of Sodium chloride, sodium bicarbonate 2%, sodium phosphate and a combination of these substances. * The other drugs used in the form of enemas include olive oil, arachis oil, turpentine, alum, tannic acid etc. * Enemas are mostly used for the following reasons * i) To relieve symptoms of constipations. * ii) To cleanse the rectum and lower intestines in preparation for an examination. * iii) To remove feces to prevent contamination during surgical procedure. ## Types of enemas * Enemas of following types: * 1) Cleansing enemas * 2) Therapeutic enemas *3) Diagnostic enemas *4) Disposable enemas. * 1) cleansing enemas: It used to evacuate feces in constipation or before an operation by stimulating peristalsis movement or through lubricating impact. * eg: olive oil, arachis oil * 2) Therapeutic enemas: For sedative purpose like chloral hydrate. * 3) Diagnostic enemas: It is used for x-ray examination of lower bowel. * eg: barium sulphate enemas. * 4) Disposable enemas: They include evacuate enemas like magnesium sulphate. * Example: A typical example of evacuant enema. * Rx * Soft Soap → 25gm * Purified water → 500ml. * Procedure: Dissolve the soap in purified water. Transfer it to a container, label and dispense. * Label: Only for rectal use. * Use: It is used as an evacuant enema. ## Syrups * Syrups are the sweet, viscous, concentrated aqueous solution of sucrose or other sugar in water or in other suitable aqueous vehicle. * When the preparation contains some medicinal substance it is known as medicated syrup. * Syrups containing 85% w/v or 66.7% w/w sucrose will retard the growth of micro-organism. ### Types of Syrup * (1) Simple Syrup: Simple syrups contain only sucrose and purified water. * IP * Sucrose → 86.7 g * Purified water → 100g. * USP → Sucrose → 85.g * Purified water → 100 ml. * (2) Medicated syrup: Syrups containing medicinal substances are called medicated syrup. It is used for therapeutic purpose. * ex: Ginger Syrup * Stronger ginger tincture → 500 ml * Syrup (q.s) → 100.0 me * 3) Flavoured syrup: Syrup containing aromatic or flavoured substances are called flavoured syrup. ### Method of Preparation * 1) Agitation Without heat: This method is used for heat labile constituents, * Sucrose and other ingredients are dissolved in purified water * through agitation. * eg: Codeine syrup, sulfate syrup etc. * 2) Solution with heat: This method is used when active constituent is neither volatile or nor heat labile. * Desired amount of sucrose is weighed and heated * purified water is added, on a water bath till a solution is obtained. * Example: Syrup IP, Acacia Syrup NF, Tolu Syrup IP. * Example: Prepare and dispense Tolu Syrup (1000ml) * Rx * Tolu balsam → 12.5g * Sucrose → 660g * Purified water → 1000ml(q.s) * Method of Preparation: Boil 100ml of purified water. Add weighed amount of tolu balsam in boiled water. * Boil for 30 minutes. * Stir * Cool and filter. * Add sufficient water to make 1000ml of solution ## Elixirs * The elixirs are clear, flavoured hydroalcoholic preparation intended for oral use, they contain one or more medicament pleasantly flavoured, coloured and contain high amount of sucrose along with some suitable antimicrobial agent. * The alcohol content in elixir vary from 5-40%. They are used to relieve cough. * Elixirs are of 2 types: * (1) Non-medicated elixir * (2) Medicated elixir. * (i) Non-medicated elixirs: They are used purely as diluting agents for drugs containing 25% of alcohol. * (ii) Medicated elixirs: They contain therapeutic active compound are known as medicated elixirs. * eg: Dexamethasone elixir USP, phenobarbital eliseir USP. * Example: Prepare and dispense high alcohol elizeir. * Rx * Compound orange spirit → 4ml * Saccharin → 3 ml * Glycerin → 200ml * Alcohol → 1000ml (q.s) * Method of preparation: Dissolve Compound orange spirit and saccharin in 100ml of alcohol and glycerin * Add * So water to make up the volume and filter ## Liniments * Liniments are solutions or mixture of various substances in oil, alcoholic solution of soap or emulsions or semi-solid preparation for external application. * They applied with friction and rubbing of the skin. * Alcoholic liniments are used generally for their counter irritant, (improves bifactention), mildy astringents and slow penetrating effect. * They easily penetrate to the skin. * Example: Prepare and dispense Camphor liniment. * Rx * Camphor → 200gm * Arachis oil → 800gm (q.s). * Method of preparation: Mix Camphor end in Arachis oil * In a vessel * Make up the volume with arachis oil. ## Lotions * Lotions are usually liquid suspension or semi-solid preparation contain medicaments, intended for external use only. * They applied on skin without friction. * Lotions are applied for local cooling, soothing or protective purpose. * Dermatologist frequently prescribe lotions for anaesthetic or antiseptic actions * Eg: Calamine lotion * Example: * Calamine → 15% w/w * Zinc Oxide → 5% w/w * Glycerin → 5% w/w. * Rose water → 100.0ml. * Method of preparation: * Mix calamine and zinc oxide in mortar. * Triturate with rose water. * Now add more of rose water to make up the volume. ## Emulsion * An emulsion is a liquid preparation containing two immiscible liquids, one of which is dispersed as globules into the other i.e dispersed medium. * Emulsion is thermodynamically unstable, to improve its stability emulsifying agents are used. * Dispersed phase and Continuous phase of an emulsion. ### Advantages * Unpalatable drugs can be administered in palatable form. * Improve the rate of absorption of drugs. * Two incompatible ingredients can be included one in each phase of an emulsion. ### Disadvantages * Emulsion should be shaken every time prior to administration. * Proper storage conditions are required. * It needs an accurate measuring device for measuring the dose for administrations. ### Types of Emulsions: * There are two types of emulsions: * (a) Oil in water type (O/W) * (b) water in oil type (W/O) * Oil in water type (O/W): In oil in water type emulsion the oil is the dispersed phase whereas water is in the continuous phase. * They are used internally. * The types of emulsions are prepared by using emulsifying agents like - gum acacia, tragacanth, methyl cellulose etc. * Water in oil type (W/O): In water in oil type emulsions, the water is in the dispersed phase, whereas oil is in the continuous phase. * These types of emulsions are mainly used externally, as lotions or creams. ## Classification or Types of Emulsions: 1) **Based on dispersed medium (phase): ** * A) O/W type → oil droplets dispersed in water. * B) W/O type → water droplets dispersed in oil. * C) multiple Emulsion → W/O/W OR O/W/O. 2) **Based on size of liquid droplets:** * (A) 0.2- 50 μm (macroemulsions) * (B) 0.01-0.2 μm. (microemulsions) * (C) 50-1000 nm (nanoemulsions). ## Emulsifying Agents: * These are the substances added to an emulsion to prevent the aggregation of the globules of the dispersed phase and hence maintain the stability of emulsion. They are also known as emulgents or emulsifiers. * An emulsifying agent mainly works act by the following mechanisms: * Reduction in interfacial tension. * Formation of a rigid interfacial film. * Formation of an electrical double layer. ## Ideal Requirements: * It should be able to reduce interfacial tension between two immiscible liquids. * It should be physically and chemically stable, inert *and* compatible with other ingredients. * It, should be non-britant and non-toxic. * It should be able to produce and maintain the required viscosity of preparation. * It should be organoleptically inert i.e should not impart any colour, odour and taste. ## Classification of Emulsifying agents: **1) Natural Emulsifying agent:** * (a) Vegetable Source → gum acacia, tragacanth, agar, starch, pectin * (b) Animal Source → Wool fat, egg yolk, gelatin. **2) Semi-Synthetic Emulsifying agent:** * eg: methyl cellulose, Na CMC ***3) Synthetic emulsifying agent:** * (a) Anionic → Sodium lauryl sulphate (SLS) * (b) Cationic → Cetrimide, Benzalkonium chloride. * (c) Non-Ionic → Glyceryl esters, span, tween. * **4) Inorganic Emulsifying agent:** * eg: Milk of magnesium, Mg oxide, Mg trioxide **5) Alcohols (polyoles):** * eg: Carbowase, cholesterol & lecithin. ## Method of Preparation: * The emulsions can be prepared by the following methods: * (A) Dry gum method/Continental Method. * (B) Wet gum method/English Method. * (C) Bottle method/Forbes Bottle Method: ### (A) Dry Gum method: * This method is used to prepare the initial or primary emulsion * Gum is triturated with oil in mortar. * Water is added at once. * Triturate continuously until get a clicking sound and white cream is formed, this is primary emulsion. * The remaining quantity of water is slowly added to form the final emulsion. * Proportion of oil: Water: Gum. ### (B) Wet Gum Method: * Triturate gum with water in a mortar to form mucilage. * Oil is added slowly and triturate. * Mix all to form primary emulsion. * Once primary emulsion formed add remaining quantity of water to make final emulsion. ### (C) Bottle or Forbes Bottle Method: * Gum + oil (dry bottle) * Shake * Water is added and shake to form primary emulsion. * Then add remaining water to make final emulsion. ## Stability of Emulsions: * There are some stability problems (problem emulsions): * Observe such as * 1) Cracking (Coalescence): * 2) Flocculation. * 3) Creaming, and Sedimentation. * 4) Breaking. * 5) Phase Inversion. ### (1) Cracking / Coalescence: * The process in which two or more droplets merge together to form a single large droplet is called coalescence. This problem can be prevented by the addition of natural gums. ### (2) Flocculation: * The association of globules within an emulsion to form large aggregates. However, these aggregates can be easily redispersed upon shaking. ### (3) Creaming and Sedimentation: * The upward or downward movement of dispersed droplets is termed creaming and sedimentation. * Creaming is defined as the upward movement of dispersed globules to form a thick layer at the surface of the emulsion. * Sedimentation defined as the downward movement of dispersed globules to form a thick layer at the bottom of the . ### (4) Breaking: * This results in complete separation of oil from water phase, so that oil floats at the top in a single layer. ### (5) Phase Inversion: * Conversion of one type of emulsion to another type (like W/O type to O/W type) is called phase inversion. This may be due to temperature or addition of strong electrolytes. * (i) coalescence (Merging of sum) * (ii) flocculation (Cluster formation) * (iii) creaming (Layer formation) * (iv) breaking *Physical instability of an *emulsion* ## Tests for Identification of Type of Emulsion: * The identification test is used for the determination of type of emulsion like W/O or O/W type. ### (1) Dilution Test: * This test is based on *solubility*. * O/W emultion can be diluted with water. * W/O emultion can be diluted with oil. ### (2) Die-Solubility Test: * Take a oil soluble dye and place a drop of dye with an emulsion and observe under microscope. * If the continuous phase appears to be red, then it is W/O emulsion. * If the droplets appears red in continuous phase then it is W/O emulsion. ### (3) Cocka Filter paper Test: * When a filter paper impregnated with cocks and dried (blue) is dipped in an emulsion change to pink, it indicates that emulsion is O/W type. This test may fail if emulsion is unstable or breaks in the presence of electrolytes. ### (4) Flourescence Test: * When oils are exposed to U.V rays they start flow fluoresce. * In case of O/W emulsion no fluorescence exhibits or bit. * In case of W/O emulsion maximum fluorescence exhibits. * This test applicable for oils that have fluorescent property. ### (5) Conductivity Test: * Water is a good conductor of electricity, whereas oil is non-conductor of electricity. * When a pair of electrodes connected to a lamp and electric source is dipped into the emulsion. * If the bulb glows, it means O/W emulsion, but if bulb not glows that means W/O emulsion ## Suspensions * A pharmaceutical suspension is a biphasic liquid dosage farm of medicament in which finely divided solid particles (ranging from 0.5 μm to 5 μm) dispersed into a liquid medium. * Solid particles act as disperse phase. * Liquid vehicle act as continuous phase. * Suspensions are meant for oral use, parenteral use, external use, opthlamicuse. * Suspension facilitates administration of insoluble, unpleasant, substances in a form which is pleasant and in taste. * It is also suitable for dermatological materials. ### Advantages of Suspensions: * Suspension improve chemical stability of certain drugs. * Eg: Procaine penicillin G * Drug in suspension have higher rate of bioavailability compared to solution > suspension > capsules > compressed tablet > coated tablet. * Eg: Protamine zinc - Insulin Suspension. * Duration and on-set of action can be controlled. * eg: Protamine zinc - Insulin Suspension. * Suspension can mask unpleasant taste of drug. * Eg: Chloramphenicol. ### Disadvantages of Suspensions: * Physical stability, sedimentation and compaction can cause problems. * They should be shaken well prior to administration. * It is difficult to formulate. * Uniform and accurate dose cannot be achieved. ## Classification of Suspension: * Oral suspension * Parentral suspension * Ophthalmic suspension * Suspension for external use. ### (1) Oral Suspension: * These suspensions are consumed by patient by oral route. * Contain generally flavouring and sweetening agent to mask bitter taste, eg: Chloramphenicol suspension. * Now-a-days suspensions are available as dry powder form. * Reconstituted by addition of specified quantity of freshly boiled and cooled water. * Eg: Antibiotic Suspension. ### (2) Parentral Suspensions: * These are administered by parentral route. * Particle size and viscosity of drug and suspension should be such that easily pass through needle of the syounge. * There should be no crystal growth in suspension during storage. * Concentration of particles in suspension between 0.5 to 30%. * It should be sterilized. ### (3) Ophthalmic Suspensions: * Ophthalmic suspension not commonly used compared to eyedrops. * Prepared only when drug is not soluble in desired solvent. * Particle size of eye-suspensions should be fine enough to not produce irritation in eye. * Suspension should be sterilized and isotonic. * Suspension for external uses: eg calamine suspension, prednisolone acetate opthapsicion. * These suspensions contain very small particles to avoid grittiness. * The solvent in these suspension evaporates from skin leaving a light deposit of medicament on the surface. ## Preparation of Suspensions: * Grinding of insoluble material with vehicle containing wetting agent to get smooth paste. * Dissolve ingredients in vehicle to get slurry. * Transfer the slurry to get graduated cylinder. * Add suspending agent or flocculating agent. * Finally adjust the volume of vehicle. ## Flocculated Suspension: * In flocculated suspension, flocs are formed (loose aggregates). * Will cause increase in sedimentation due to increase in size of particles. * Hence, flocculated suspension sediment more rapidly. ## Deflocculated Suspensions: * In this individual particles are settle. * So, rate of sedimentation is slow. * Which prevent entrapping of liquid medium which make it difficult to re-dispersed by agitation. * This is called caking or claying. * In deflocculated suspension, larger particles settle fast and smaller remain in supernatant liquid, so supernatant appears cloudy. ## Difference between flocculated and deflocculated suspension: ### Flocculated * Particles form loose aggregates. * And form a network like structure. * Rate of sedimentation is high. * Sediment is rapidly formed. * Sediment loosely packed and doesn't form hard cake. * Sediment is not redispersed. * Suspension is not pleasing in appearance. * Floccules stick to the sides of the bottles. ### De-floculated * Particles exsist as separate entities. * Rate of sedimentation is slow. * Sediment slowly formed. * Sediment is very closely packed and a hard cake is formed. * Sediment is difficult to redisperse. * Suspension is pleasing in appearance. * They do not stick to the sides of the bottle. ## Stability Problems with Suspensions: * There are some problems which are associated with the stability of suspension. * 1) Caking and poor redispersibility. * 2) Cap locking. * 3) Colour change. * 4) Crystal growth. * 5) Deflocculation * 6) Rapid settling. * 7) Change in particle size. * 8) Foaming. ### 1) Caking: * Caking is a compact mass of insoluble solids powder formed generally in deflocculated suspension due to the smaller size of the particles. * Remedy/overcome: This problem can be overcome by the use of flocculating agent and using viscosity importing agent that will resist caking of particles or particle-particle interaction. ### 2) Cap locking: * It is a problem where particles gets crystallise on the threads of the bottle cap and interface in cap cover removal. * Remedy: It can be preventing by using different vehicle containing sucrose, glucose. ### 3) Colour change: * Light sensitive colour may be changed in presence of light, due to the increased surface area. Some colour may be changed. * Remedy: Staring in cool and dark palace. ### 4) Crystal growth: * Sometime there is crystal growth during storage which can be due to following reasons. * (i) Fluctuation in temperature (ii) change in pH (iii) Due to impurities (iv) poor solubility. * Remedy: By adding surfactants, by controlling solubility, by controlling pH, by preventing temperature. ### 5) Deflocculation: * Deflocculation take place due to the following reasons. * 1) Change in pH * 2) Adding of excess electrolytes. * 3) Due to drug degradation. * Remedy: By using flocculating agent, by using electrolytes, by using polymers. ### 6) Rapid settling: * Some suspension particles settle fast. * Remedy: By decreasing the particle size, by using viscosity imparting agents. ### 7) Change in Particle Size: * Sometime the particle size increase because of aggregation of small particles. * Remedy: By using viscosity imparting agent.