Diploma in Pharmacy FFT1214 Pharmaceutics II PDF

Diploma in Pharmacy FFT1214 Pharmaceutics II Please do not reproduce, redistribute or share without the prior express permission of the author. Chapter 1 Pharmaceutical Solutions FFT1214 Pharmaceutics II Please do not reproduce,...

Diploma in Pharmacy FFT1214 Pharmaceutics II Please do not reproduce, redistribute or share without the prior express permission of the author. Chapter 1 Pharmaceutical Solutions FFT1214 Pharmaceutics II Please do not reproduce, redistribute or share without the prior express permission of the author.  Learning outcome After completing this lesson, the students should be able to: 1. Define pharmaceutical solution preparations. 2. Describe solubility. 3. Explain the methods to improve solubility 4. Identify the different solution / mixture pharmaceutical dosage forms 5. State the problems that lead to instability of solution dosage forms Please do not reproduce, redistribute or share without the prior express permission of the author.  Pharmaceutical Solution Dosage Forms Definitions Solution: A solution is a clear, homogeneous mixture that is prepared by dissolving a solid, liquid or gas in another liquid. Solute: A component present in lesser amount is known as solute. Solvent: A component of a solution, present in large amounts is known as solvent. Please do not reproduce, redistribute or share without the prior express permission of the author. Please do not reproduce, redistribute or share without the prior express permission of the author. Please do not reproduce, redistribute or share without the prior express permission of the author. Pharmaceutical Solution Dosage Forms Please do not reproduce, redistribute or share without the prior express permission of the author. Please do not reproduce, redistribute or share without the prior express permission of the author.  Type of Solution ? Please do not reproduce, redistribute or share without the prior express permission of the author. Please do not reproduce, redistribute or share without the prior express permission of the author. Solid in liquid Gas in liquid Liquid in liquid Please do not reproduce, redistribute or share without the prior express permission of the author.  Pharmaceutical Solution Dosage Forms Advantages of solutions The doses can be easily adjusted according to the needs of the patients. The onset of action is faster than solid or capsule because it is already in a solution form. Please do not reproduce, redistribute or share without the prior express permission of the author.  Pharmaceutical Solution Dosage Forms Disadvantages of solutions Difficult to carry and the chance of breakage (for glass containers) is high. Less stable as compared to solid dosage forms, because deterioration is faster in solution. Solutions are a suitable media for the growth of microorganisms and therefore need the addition of a suitable preservative. Accurate doses will depend on the ability of the patient to use a measuring device (such as a 5 ml spoon or a volumetric dropper). Please do not reproduce, redistribute or share without the prior express permission of the author.  Solubility Solubility is a measure of how readily one chemical substance can dissolve another Please do not reproduce, redistribute or share without the prior express permission of the author.  Solubility When an excess of a solid is brought in contact with the solvent and the solid is allowed to dissolve in solvent, after some time a stage is reached when an equilibrium is established between the solute and the solvent, and no more solute dissolves. This solution is said to be saturated at that temperature. The extent to which the solute dissolves to produce saturated solutions at a given temperature is known as its solubility. Water is considered to be the most suitable vehicle for the preparation of liquid formulations, but a large number of modern drugs are insoluble in water. So, the solubility of drug in water can be increased by modifying certain factors that affect solubility. Please do not reproduce, redistribute or share without the prior express permission of the author.  Methods / Techniques to Improve Solubility 1. Solubilization 2. Co-solvency 3. Complexation 4. Hydrotropy 5. Chemical modification of the drug 6. pH adjustment Please do not reproduce, redistribute or share without the prior express permission of the author.  Methods / Techniques to Improve Solubility 1. Solubilization Solubilization is defined as the process of enhancing the solubility of a very slightly soluble or an insoluble drug in a suitable solvent by adding a surface-active agent to obtain a desired formulation. Example: Adding surfactant / surface-active substance such as sodium lauryl sulphate (SLS), sodium lauryl ether sulphate (SLES) etc. helps to increase the solubility of many poorly soluble drugs. Please do not reproduce, redistribute or share without the prior express permission of the author.  Methods / Techniques to Improve Solubility 2. Co-solvency The solubility of poorly soluble drugs in water can be increased by mixing it with some water miscible solvent in which the drug is readily soluble. This phenomenon is called co-solvency. Examples of co-solvents include glycerin, alcohol, propylene glycol etc. Please do not reproduce, redistribute or share without the prior express permission of the author.  Methods / Techniques to Improve Solubility 3. Complexion An insoluble substance is added together with a soluble ingredient to form a complex which is then readily soluble in water. Example: - Iodine (I2) is insoluble in water - Iodine (I2) + Potassium iodide (KI) Potassium Tri-iodide ( KI.I2, A complex, soluble in water) Please do not reproduce, redistribute or share without the prior express permission of the author.  Methods / Techniques to Improve Solubility 4. Hydrotropy Hydrotropy refers to the addition of large amounts of a second solute which results in an increase in the aqueous solubility of an existing solute. Concentrated aqueous hydrotropic solutions of sodium benzoate, sodium salicylate, urea, nicotinamide, sodium citrate have been observed to enhance the solubilities of many poorly water-soluble drugs. Please do not reproduce, redistribute or share without the prior express permission of the author.  Methods / Techniques to Improve Solubility 5. Chemical modification of a drug Many drugs are poorly soluble in water and hence they are converted into their salt forms to improve solubility. Example: - Alkaloids such as atropine and morphine are poorly soluble. - But their alkaloidal salts atropine sulphate and morphine hydrochloride are freely soluble in water. Please do not reproduce, redistribute or share without the prior express permission of the author.  Methods / Techniques to Improve Solubility 6. PH adjustment By increasing or decreasing the pH, solubility may be increased. Example: The solubility of weakly basic drugs increases in acidic solutions and solubility of weakly acidic drugs increase in alkaline pH conditions. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 1. Mixtures Definition: A mixture is a liquid preparation used for oral administration in which medicament or medicaments are dissolved or suspended in a suitable vehicle. Generally, several doses are dispensed in a bottle. In case a bottle contains one dose it is called “draught”. Mixtures are formulated for short term use only, like in cough, diarrhea etc. Example - Gelusil liquid, Benadryl cough mixture etc. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms Advantages of mixtures They have faster onset of action than solid dosage forms, as it doesn't require time for disintegration in the body Certain substances can only be given in liquid form because they are inconvenient to administer in any other form due to their liquid nature and large dose. Some medicaments like potassium iodide may cause irritation in stomach in the powder form or tablet form. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms Formulation of mixtures i. Vehicle a. Purified water Purified water is prepared from potable water, purified to meet pharmacopeial requirements. Mixtures should NOT be prepared with potable water. If you can drink it or cook with it, it’s potable. water that is not Sometimes freshly boiled and cooled purified water is contaminated with used as a vehicle which is free from vegetative organic, inorganic, radiological, or microbiological pollutants and bacteria. does not present any differences in taste, smell, or appearance. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms b. Aromatic water These are saturated solutions of volatile oil and volatile substances in purified water. Aromatic water is mainly used for its flavoring properties. Some of the aromatic waters possess carminative and preservative properties as well. So, an aromatic water is included to increase the palatability, flavour and preservation of mixture. Example: Camphor water, peppermint water etc. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms c. Medicated water Sometimes a vehicle with definite therapeutic activity is prescribed. For example, orange peel infusion (carminative) and senega infusion (expectorant) are used as vehicles for the preparation of mixtures. These infusions are prepared by diluting one (1) volume of compound infusion with seven (7) parts of purified water. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms ii. Adjuncts/excipients Adjuncts are substances which do not have any medicinal value and are generally used to improve the stability, colour, and flavour of the mixture. a. Chemical stabilizer Certain substances having antioxidant or reducing properties are used for the chemical stability of the product. For example, ascorbic acid ( 0.1% ) is included in ferrous sulphate mixture to prevent the oxidation of ferrous to ferric. (Anti-oxidant) Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms b. Colouring agent No special colouring agents are added to mixtures as most of them contain coloured medicaments. c. Flavouring Agent Following flavouring agents are added in mixture. Lemon spirits, orange spirits etc. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms d. Preservatives Diluted vegetable extracts and flavouring agents are the source of growth of bacteria and fungi. Hence chloroform (0.25% v/v) and benzoic acid (0.1% w/v) are used to preserve such mixtures. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 2. Syrups Definition: Syrup is a concentrated, sweet, viscous solution of sucrose in purified water. Simple syrup: When a syrup contains purified water and sucrose only it is called simple syrup. Medicated syrup: When the simple syrup contains medicaments then it is called as medicated syrup. Eg. Ginger syrup Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 2. Syrups The concentration of sucrose in simple syrup according to BP is 66.7%w/w. The main advantage of syrup is, it is palatable. Simple syrup contains 66.7% w/w sucrose, have high osmotic pressure which prevent the growth of bacteria. So simple syrup does not need any preservative. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 3. Elixirs Definition: Elixirs are clear, sweetened, aromatic, hydro-alcoholic liquids for oral use. Main ingredients in elixirs are ethanol, water. Usually, it contains potent drugs like antibiotics, antihistamine etc. Apart from alcohol and water it also contains: - Chemical stabilizers – example: antioxidants for stabilizing elixir. - Flavoring agents - example: lemon syrup. - Preservatives - example: glycerol, propylene glycol. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 4. Linctus Definition: Linctuses are liquid, oral, viscous preparations used for the treatment of cough. They usually contain medicaments such as: Demulcents - internal soothening agent. Sedatives - produce sleep. Expectorants - coughing and spitting out the sputum (thick viscous matter) from lungs. Linctuses should be taken undiluted, sipped and swallowed slowly. Eg. Codeine linctus B.P.C Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 5. Liniments Definition: liniments are liquid or semi-liquid preparations used for external application to the skin. They usually contain substances possessing analgesic, rubefacient or smoothing properties. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 5. Liniments Liniments are usually applied to the skin “with friction” and rubbing of the skin. Arachis oil is used in some liniments which spreads more easily on the skin. They should not be applied to the broken skin. The bottle should be labeled “for external use only” Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 6. Lotions Definition: lotions are usually liquid preparations used for external application “without friction”. They are applied directly to the skin with the help of some absorbent material like cotton. Usually, lotions are used for local cooling, soothing or protection purposes. Alcohol is sometimes included in the lotions for the cooling purpose. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 6. Lotions The label should include: For external use only. Shake well before use (for suspensions). Example: Salicylic acid lotion 2% (Anti-aging) Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 7. Drops These are liquid preparations for oral administration. Generally potent medicaments like vitamins and antibiotics are available as drops. Since it contains potent medicaments, a dropper with graduations (in fractions of a milliliter) is used. Example: Multivitamin Drops. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 8. Draughts It is a liquid preparation to be taken as a single dose. They are usually available in 30 - 50 ml containers. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 9. Mouth Washes Definition : These are aqueous solutions with a pleasant taste and odour used to clean and deodorize the buccal cavity. Generally, it contains antibacterial agents, alcohol, glycerin, sweetening agent etc. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 10. Gargles They are aqueous solutions used for the treatment of infections in the throat. Usually they are concentrated solutions, which are diluted before use. Usage: Take the gargle in the mouth, keep in contact with the mucous membrane of the throat and allow to remain there for a few moments. The contents are to be thrown out of the mouth after the required contact time. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 11. Throat paints Definition : Throat paints are liquid, viscous preparations used for the treatment of mouth and throat infections Glycerin is commonly used as a base; being viscous, it will adhere to the membrane for a longer time. Example : Compound iodine paint [Mandl’s paint] BPC, Clotrimazole mouth paint. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 12. Douches A douche is a medicament solution used for rinsing body cavities. The word douches is often used for vaginal solution and called “vaginal irrigation”. It is also used in other body cavities like ear, nose and eye for cleansing purpose. Please do not reproduce, redistribute or share without the prior express permission of the author.  Types of Solution Dosage Forms 13. Enema Enemas are aqueous or oily solutions or suspensions intended for the introduction to the rectum for their purgative, sedative, anthelmintic or anti-inflammatory purpose. They act by stimulating peristalsis, by lubricating impacted faeces, Eg. Olive oil and arachis oil enemas Please do not reproduce, redistribute or share without the prior express permission of the author.  Problems leading to instability of solutions After preparing a solution it must be stable for the desired time. There are two types of stability problems Physical instability Chemical instability Please do not reproduce, redistribute or share without the prior express permission of the author.  Problems leading to instability of solutions Physical stability problems: - Colour change - Flavour change - Presence of cloudiness - Growth of microorganism Chemical stability problems - Hydrolysis - Oxidation - Reduction - Polymerization Because of these reasons it is difficult to prepare liquid dosage forms with an extended stability Please do not reproduce, redistribute or share without the prior express permission of the author. Presence of cloudiness Chemical change Colour change Please do not reproduce, redistribute or share without the prior express permission of the author.  References Aulton M (2002) Pharmaceutics. 2nd edition. Churchill Livingstone , Spain (Tablets and Compaction Page No.397-440 ) Banker G.S., Rhodes, C.T (2002). Modern Pharmaceutics. 4th Edition. Churchill Livingstone Please do not reproduce, redistribute or share without the prior express permission of the author. Key terms related to the topic Please do not reproduce, redistribute or share without the prior express permission of the author. Q&A Session Please do not reproduce, redistribute or share without the prior express permission of the author.  Thank you Address Telephone Website Lot 33-40, Blok C, Plaza Juta, +6088 431 025/35 kk.cyberjaya.edu.my KM 7.2 Off Jalan Tuaran, 88400 Likas, Kota Kinabalu, Email Sabah, Malaysia [email protected]