Liquid Dosage Forms PDF

Liquid Dosage Forms By Dr. Mohamed Ali Attia Shafie Prof. of Pharmaceutics ١ ٢  Pharmaceutical Solutions Aqueous Sweet &/or Viscid Nonaqueous 1. Douches 1. Syrups 1. Elixirs 2. Enemas 2. Hon...

Liquid Dosage Forms By Dr. Mohamed Ali Attia Shafie Prof. of Pharmaceutics ١ ٢  Pharmaceutical Solutions Aqueous Sweet &/or Viscid Nonaqueous 1. Douches 1. Syrups 1. Elixirs 2. Enemas 2. Honeys 2. Spirits 3. Gargles 3. Mucilages 3. Collodions 4. Mouthwashes 4. Jellies 4. Glycerins 5. Nasal washes 5. Liniments 6. Juices 6. Oleo Vitamin 7. Sprays 8. Otic solutions 9. Inhalations ٣  Solutions are: Dosage forms prepared by dissolving the active ingredient(s) in an aqueous or non aqueous solvent. ٤ Solutions can be formulated for different routes of administration Orally: Syrups, elixirs, drops In mouth and throat: Mouth washes, gargles, throat sprays. In body cavities: Douches, enemas, ear drops, nasal sprays. On body Surfaces: Collodions, lotions. ٥ Advantages of SoIutions (1) Easier to swallow therefore easier for: children - old age - unconscious people. (2) More quickly effective than tablets and capsules. (3) Homogenous therefore give uniform dose than suspension or emulsion which need shaking. (4) Dilute irritant action of some drugs (aspirin, Kl, KBr) ‫ز‬ minimize adverse effects in the GIT like KCl. ٦ Disadvantages of SoIutions (1) Bulky therefore difficult to transport and store. (2) Unpleasant taste or odours are difficult to mask. (3) Needs an accurate spoon to measure the dose. (4) Less stable than solid dosage forms. major signs of instability: colour change, precipitation microbial growth chemical gas formation ٧ Additives Buffers To resist any change in pH. Isotonicity modifiers Solutions for injection Application to mucous membrane Large-volume solutions for ophthalmic application Most widely used isotonicity modifiers are: dextrose and NaCl Viscosity enhancement It is difficult for aqueous-based topical solutions to remain on the skin or in the eye (why?) therefore low concentrations of jelling agents are added to increase the viscosity of the product. ٨  Preservatives Solution may become contaminated for a number of reasons: 1. Raw materials used in the manufacture of solutions are excellent growth media for bacterial substances such as gums, dispersing agents, sugars and flavors 2. Equipment, environment and personnel contribute to product contamination. 3. Consumer use may result in the introduction of microorganism. ➔ a preservative should be added to the product Preservative used should be: 1. effective against a wide spectrum of microorganisms 2. stable for its shelf life 3. non toxic, non sensitizing 4. compatible with the ingredients in the dosage form 5. free of taste and odor ٩ Preservative used should be: 1. effective against a wide spectrum of microorganisms 2. stable for its shelf life 3. non toxic, non sensitizing 4. compatible with the ingredients in the dosage form 5. free of taste and odor. Preservatives may be used alone or in combination to prevent the growth of microorganisms. ١٠  Alcohols ✴Ethanol is useful as a preservative when it is used as a solvent. It needs a relatively high concentration (> 10%) to be effective. ✴Propylene glycol also used as a solvent in oral solutions and topical preparations. It can function as a preservative in the range of 15 to 30%. It is not volatile like ethanol. ١١  Acids ✴Benzoic acid and sorbic acid have low solubility in water. ✴They are used in a concentration range from 0.1 % to 0.5%. ✴Only the non-ionized form is effective and therefore its use is restricted to preparations with a pH below 4.5 (WHY?). ١٢  Esters ✴Parabens : are esters (methyl, ethyl, propyl and butyl) of p-hydroxybenzoic acid. ✴They are used widely in pharmaceutical products and are effective and stable over a pH range of 4 to 8. ✴They are employed at concentrations up to about 0.2%. Frequently 2 esters are used in combination in the same preparation WHY? - To achieve a higher total concentration - To be active against a wider range of microorganisms. ١٣  Quaternary Ammonium Compounds ✴Benzalkonium chloride is used at a relatively low concentration 0.002 to 0.02%. ✴This class of compounds has an optimal activity over the pH range of 4 to 10 and is quite stable at most temperatures. ✴Because of the cationic nature of this type of preservative it is incompatible with many anionic compounds. ١٤  Antioxidants Co Vitamins, essential oils & almost all fats and oils can be oxidized. Oxidation reaction can be initiated by: 1. heat: maintain oxidizable drugs in a cool place 2. light: use of light- resistant container 3. heavy metals (e.g. Fe, Cu): effect of trace metals can be minimized by using citric acid or ethylenediamine tetr acetic acid (EDTA) i.e. sequestering agent. Antioxidants as propyl & octyl esters of gallic acid, tocopherols or vitamin E, sodium sulfite, ascorbic acid (vit. C) can be used. ١٥ a­  Antioxidants Antioxidants as propyl & octyl esters of gallic acid, tocopherols or vitamin E, sodium sulfite, ascorbic acid (vit. C) can be used. Advantages: Colourless, highly water soluble, stable over a wide pH range (4-8), increase the viscosity, masks both salty and bitter taste, has soothing effect on throat. ١٦  Sweetening agents Sucrose is the most widely used sweetening agent. Polyhydric alcohols (sorbitol, mannitol and glycerol) possess sweetening power and can be used for diabetic preparations. ١٧  Flavors and perfumes ✴Mask unpleasant taste or odor. ✴ Enable the easy identification of the product. ✴ Natural products: fruit juices, aromatic oil (peppermint, lemon). ✴ Artificial perfumes are cheaper, more readily available and more stable than natural products. ١٨  Stability of solutions Both physical and chemical stability of solutions in their containers is very important. A solution must retain its clarity, colour, odour, taste and viscosity over its shelf life. ١٩  Classification of Solutions According to Vehicle (a) Aqueous solutions. (b) Non-aqueous solutions. ٢٠  Aqueous Solutions Aqueous solutions are homogeneous mixtures that are prepared by dissolving a solid, liquid or gas in an aqueous medium (vehicle). Vehicle: This may be water, aromatic water or extracts. ٢١  WATER Water is used both as vehicle and as a solvent for the desired flavoring or medicinal ingredients. Advantages: Tasteless, odourless, lack of pharmacological activity, neutral and very cheap ٢٢  Types of Water 1. Tap Water It is not permitted to use tap water for the dispensing of pharmaceutical dosage forms due to its possible bacterial contamination and the presence of dissolved salts that destroy the active ingredients or enhance their decomposition. ٢٣  Types of Water 2. Freshly Boiled and Cooled Water Boiling is seldom used to destroy Vegetative bacteria. But, on storage for long time spores may yield vegetative microorganism. ٢٤  Types of Water 3. Purified Water ✴Must be used for most pharmaceutical operations and in all the tests and assays. ✴Such water is prepared by distillation, deionization or reverse osmosis. ✴"Hard" waters are those that contain the Ca and Mg cations. ✴“Alkaline" waters are those that contain bicarbonates as the major impurity. ✴Ultraviolet energy, heat or filtration (Millipore filtration) can be used to remove or kill the microorganisms present in the water. ٢٥  Types of Water Water for injection ✴Must be used for the formulation of parental solutions. ‫مخلفات بكتريا‬ ✴It is obtained by sterilizing pyrogen-free distilled water. ٢٦ ٢٧  Aromatic Waters ✴ Aromatic waters (medicated waters) are clear, saturated aqueous solution of volatile oils or other aromatic or volatile substances. ✴ They are used principally as flavored or perfumed vehicles. ✴Volatile oils solutions represent an incompatibility problem of salting out. This occurs after the incorporation of a very soluble salt in their solution. ٢٨  Aromatic Waters ✴Aromatic water will deteriorate with time therefore: 1. should be made in small quantities 2. protected from intense light and excessive heat by storing in air tight, light resistant containers. ✴If they become cloudy or otherwise deteriorate; they should be discarded. Deterioration may be due to volatilization, decomposition or mould growth. ٢٩  Methods of preparation of Aromatic Waters 1. Distillation process (Stronger Rose Water NF). ✴ The drug should be coarsely ground and mixed with sufficient quantity of purified water in the distillation unit. ✴ After distillation any excess oil in the distillate is removed by filtration. ✴ Drug should not be exposed to the action of direct heat during distillation; otherwise, the odor of the carbonized substance will be noticeable in the distilled aromatic water. ✴ If the volatile principle in the water are present in small quantities the distillate is returned several times to the still with fresh portions of drug. ٣٠  Methods of preparation of Aromatic Waters 2. Solution process (Peppermint water) Aromatic water may be prepared by shaking volatile substance with purified water. The mixture is set aside for 12 hours & filtered. Talc (inert) may be used to increase the surface of the volatile substance, insure more rapid saturation of the water and act as a filter aid. ٣١  Methods of Preparation of Solutions (a) Simple solution. (b) Solution by Chemical Reaction. (c) Solution by Extraction. ٣٢  Methods of Preparation of Solutions (a) Simple Solution Solutions of this type are prepared by dissolving the solute in a suitable solvent (by stirring or heating). The solvent may contain other ingredients which stabilize or solubilize the active ingredient e.g. solubility of Iodine is 1: 2950 in water however, it dissolves in presence of KI due the formation of more soluble polyiodides (KI.I2 KI.2I2 KI3.I3 KI.4I4).[ Strong Iodine Solution USP (Lugol's SoIution)]. ٣٣  Methods of Preparation of Solutions (b) Solution by Chemical Reaction These solutions are prepared by reacting two or more solutes with each other in a suitable solvent e.g. Calcium carbonate and lactic acid used to prepare Calcium lactate mixture. WHY? (c) Solution by Extraction Plant or animal products are prepared by suitable extraction process. Preparations of this type may be classified as solutions but more often, are classified as extractives. Extractives will be discussed separately. ٣٤ 1.Infusion An infusion is a dilute solution Of the readily soluble constituents of crude drugs. Fresh infusions Are prepared by macerating the solids for a short period of time with either cold or boiling water. The infusion should be prepared in earthenware vessels, thoroughly warmed before use. Drugs containing an active ingredients which is easily soluble in cold Water ( e.g. Quassia wood ) and those containing quantity of starch are prepared with water at room temp. ٣٥  Infusion ( Cont.. ) Infusions should be freshly prepared or Infusions which are constantly ordered can be preserved by sterilization. Concentrated infusions Are preparations which, when diluted with seven times their volume of water, yield products representing approximately the corresponding infusions of the British Pharmacopoeia. ٣٦  2. Decoction A decoction is an herbal preparation similar to an herbal infusion except that it more potent in its strength and therapeutic properties. Some parts of an herb can not be completely extracted in a solution with an ordinary infusion processes, specially when you are using tougher herbal parts like the root, bark, seeds, dry fruits. ٣٧ 3. Maceration Process ‫مذيب‬ ٣٨ Soxhlet Percolator ٣٩