Pharmaceutics I Lecture 1 - Introduction to Solutions PDF

Pharmaceutics I Lecture 1 Dr. Ghada M. El Zaafarany Associate Professor of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy Ain Shams University 1  Pharmaceutical Solutions 2 ❖ What are solutions?...

Pharmaceutics I Lecture 1 Dr. Ghada M. El Zaafarany Associate Professor of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy Ain Shams University 1  Pharmaceutical Solutions 2 ❖ What are solutions? Are homogeneous liquid preparations that contain one or more chemical substance (s) (solute) completely dissolved in a suitable solvent (vehicle) or mixture of miscible solvents 3 ❖ Classification of solutions: 1) According to solvent type: Aqueous & Non-aqueous 2) According to use: Internal & External 3) According to route of administration ✓ Oral: syrups, aromatic waters, elixirs, spirits & oleo vitamins ✓ In mouth & throat: Mouth washes & gargles ✓ In body orifices: Douches, enemas, ear drops ✓ On body surfaces: lotions, liniments, glycerites & collodions 4  Advantages of solutions ❖ Compared to solid dosage forms (e.g. tablets & capsules): 1. Easier swallowing esp in pediatrics & geriatrics 2. More rapid action due to faster absorption ❖ Compared to suspensions: 1. No need to shake the bottle before use → the drug is uniformly distributed 2. More accurate dose 5  Disadvantages of solutions 1. Difficult masking of bad taste 2. Are too bulky to carry with risk of container breakage 3. Need accurate spoon to measure the dose → dose measurement depends on the patient’s accuracy (multi dose container) 4. Less stable than solid dosage forms → more prone to microbial contamination → 6 so a preservative is usually needed  Methods of preparation Solution by Simple Solution by chemical solution extraction reaction 7 (A) Simple solution: ▪ Solution is prepared by directly dissolving solute in the solvent: Solid ingredients are dissolved in a quantity (2/3) of the vehicle (1ry solution) → other liquid ingredients are added → the solution is completed to the final volume with the vehicle. ▪ When mixed solvents are used: - each solute should be dissolved in the solvent in which it is most soluble - when viscous solvents are included it is better to use the less viscous vehicles to make the primary solution E.g. Calcium hydroxide solution U.S.P (lime water) Dissolve 3 gm of Ca (OH)2 in 1L of cool purified water (exothermic solubility) N.B. The solution must be kept in: well closed container to avoid CO2 which precipitates as CaCO3 cold place to maintain the solubility of Ca(OH)2 ▪ Uses: 1. Topical: in lotions used as an astringent 2. Oral: as a source of calcium - mild antacid 9 (B) Solution by chemical reaction Prepared by reacting solutes with each other in a suitable solvent to increase the solubility E.g. Lugols’ Solution (Strong Iodine solution) Iodine is insoluble in water so a solubilizing agent (potassium iodide) is added to form polyiodide complex (a soluble form of I2 that has similar therapeutic effect): I2 (insoluble) + KI → KI3 (tri-iodide complex) (soluble) Uses: 1. Topically: germicide (antiseptic) 2. Orally: treatment of hyperthyroidism 10 C) Solution by Extraction: ▪ Solutions of natural origin (plant or animal) are prepared by extraction with a selective solvent (extractives) → Galenicals 11  SOLVENTS used in solutions 1) Water ► Purified ► WFI ► Freshly boiled & cooled ► Tap A) Purified water : Is pure water free from micro-organisms, ions (cations & anions) and salts → NOT STERILE Is the most commonly used vehicle (mainly oral & topical solutions) Advantages: tasteless, odorless, cheap, no 12 pharmacological activity & non-irritant B) Water for Injection (WFI): Is purified water sterilized by UV radiation, heating or filtration → Sterile pyrogen-free purified water → Used for parenterals & eye drops C) Freshly boiled and cooled water: Boiling destroys micro-organisms (not spores) Not a widely used vehicle because it contains salts & ions → may affect active ingredients Must be used fresh (directly after cooling) → on storage 13 spores may yield micro-organisms D) Tap water: Not used as a pharmaceutical vehicle because: 1. It maybe contaminated by bacteria 2. It contains dissolved salts that may affect active ingredients (may cause chemical incompatibilities e.g. precipitation & discoloration) Uses: washing of tools & equipment (should 14 never come in contact with the final product)  Methods of preparation of purified water 1- Distillation (Distilled water) - consists of: pot (water is heated) + condenser (heated vapour is cooled back to the liquid state) + receiver (distillate is collected) - The first distillate portion is discarded → contains volatile impurities - Last amount is discarded → distillation to dryness decomposes remaining solid impurities → contamination of distillate  2- Ion exchange (Deionized water) (Demineralized) Involves passing water through a column of cation and anion exchangers (water insoluble polymerized resins of high molecular weight) (a) Cation exchange resins (acidic resin) → permit removal of cations (Ca++, Mg++) in tap water by exchanging with hydrogen ion from the resin (e.g. sulphonated & carboxylic resins) H – Resin + M+ + X- + H2O → M – Resin + H+ + X- + H2O (b) Anion exchange resins (basic resin) → permit removal of anions (Cl-) (e.g. amino resins) Resin 16 – NH2 + H+ + X- + H2O → Resin – NH2.HX + H2O (pure) 17  3- Reverse Osmosis A pressurized stream of water is passed through a filter (semi-permeable) → this removes all pyrogens, salts & ions Solutes are retained on the pressurized side of the membrane → the pure solvent is allowed to pass to the other side This membrane does not allow large molecules through the pores (holes), but allows smaller solvent molecules to pass freely 18 2) Alcohol Has high dissolving properties → forms H bonds like water Used as: 1. Co-solvent to increase solubility of non- electrolytes 2. Hydroalcoholic solution: The solvent is a mixture of water & alcohol A) Ethyl alcohol (contains 5% water) Preservative effect (> 10-12%) Useful in extraction of crude drugs → it is a selective solvent → dissolves active ingredients (resin – volatile oil – alkaloid – glycoside) → does not dissolve inert constituents (cellulose – 19 albumin – starch ) B) Absolute alcohol (dehydrated alcohol) (100%) Free from water → has greater range of solvent power Used in research – analysis C) Isopropyl alcohol Toxic → used externally only (in some liniments and lotions) Contains < 1% water 20 3) Glycerin A viscous liquid that is an excellent solvent → comparable to alcohol Is a preservative in high concentration (> 20%) When used for extraction it is not selective → it dissolves inert ingredients, as well as, active ingredients Acts as: Solvent – Co-solvent – Preservative 4) Propylene glycol → A substitute for glycerin 21  Components of Pharmaceutical solutions Drug Solvent Formulation Additives Sweetener Isotonicity Viscosity Buffer Preservative Antioxidant Flavour modifier Enhancer Colour  Solution additives 1- Buffers: Are materials that enable the solution to resist any change in pH (e.g. solutions formulated for application to mucous membranes) Example Phosphate buffer 2- Isotonicity modifiers: Solutions for injection and application to mucous membranes (e.g. nasal drops) must be made isotonic with tissue fluids to avoid pain and irritation Examples sodium chloride & dextrose 23  3- Stabilizers (Antioxidants): An ideal antioxidant should be: 1. non-toxic & non-irritant 2. effective at low concentrations 3. odourless & tasteless 4. soluble in the vehicle Examples Ascorbic acid, Citric acid & Sodium sulphite Vitamins, essential oils and fats can be easily oxidized → this reaction is catalyzed by heat & light → incorporation of antioxidant is so important  4- Preservatives: Are ingredients added to solutions to prevent contamination An ideal preservative should be: 1. effective against wide spectrum of M.O. 2. non-toxic & non-irritant 3. tasteless and odorless 4. compatible with other ingredients 5. soluble in the solvent 6. effective in its unionized form (ionized form can't penetrate M.O. cell membrane) 25 Examples: ► Alcohols ► Acids ► Esters ► 4ry ammonium (1) Alcohols Ethanol (used in concentration > 10%) Propylene glycol & glycerol (used in concentration 15- 30%) Chlorobutanol (used in low concentration 1%) (2) Acids Benzoic acid (0.1-0.5%) → effective at pH < 4.5 (unionized 26 form) (3) Esters Methyl, ethyl, propyl and butyl parabens (parahydroxy benzoic acid esters) → used in 0.2% concentration Usually used in combinations of 2 to be active against a wide range of M.O. Activity is reduced in: a) alkaline medium → decomposition of ester group (benzoic acid becomes ionized) b) presence of non-ionic SAA → binding (4) Quaternary ammonium compounds Benzalkonium chloride: - Is a cationic SAA → incompatible with anionic compounds - Used externally in low concentration (0.02%) 27  5- Viscosity modifiers: Are gelling agents used in low concentrations to increase the viscosity of a solution (in skin, ear or eye preparations) E.g. povidone and hydroxyethylcellulose 6- Sweetening agents: ► Natural sweetners: sucrose (most common) ► Artificial sweeteners: saccharine, aspartame ► Polyhydric alcohols: sorbitol, mannitol & glycerol 7- Colouring agents: Added to solutions for external use in the mouth as a warning against swallowing (E.g. Amaranth) 8- Flavouring agents: Used 28 to mask unpleasant taste (E.g. Peppermint oil)