Unit 6.1 LDF Aqueous, Viscid, Non-Aqueous Solutions PDF

8.1: AQUEOUS, NON-AQUEOUS & SWEET/VISCID SOLUTIONS Unit 8: LIQUID DOSAGE FORMS Solutions  Liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents.  Classified based on:  Use – oral, otic, ophthalmic, topi...

8.1: AQUEOUS, NON-AQUEOUS & SWEET/VISCID SOLUTIONS Unit 8: LIQUID DOSAGE FORMS Solutions  Liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents.  Classified based on:  Use – oral, otic, ophthalmic, topical  Composition - syrups, elixirs, spirits, aromatic waters, tinctures, fluidextracts STEAFS Solutions can be formulated for different routes of administration. SED Orally: Syrups, elixirs, drops MGT In mouth and throat: Mouth washes, gargles, throat sprays Need In body cavities: Douches, enemas, ear drops, nasal sprays Ch On body Surfaces: Collodions, lotions Factors Affecting Solubility 1. Temperature 2. Physicochemical Properties of Solute and Solvent 3. Pressure 4. pH of the solution 5. Particle size of the substance 6. Extent of agitation Relative Terms of Solubility (USP) Parts of Solvent Descriptive Term Required for 1 part of Solute Very soluble 10,000 Solvents for Liquid Preparations Ethyl alcohol 1. Alcohol, USP – 94.9 – 96% ETOH Ethanol  Dehydrated Alcohol, USP – nlt 99.5% C2H5OH Alcohol 2. Diluted Alcohol, NF – approx. 49% ROH  Equal volumes of Alcohol, USP + Purified Water, USP 3. Rubbing Alcohol –70% ETOH + denaturants 4. Glycerin, USP (Glycerol) 5. Isopropyl Rubbing Alcohol – 70% isopropyl alcohol 6. Propylene Glycol, USP 7. Purified Water, USP – nmt 0.001% of residue (1 mg/100 mL)  used aqueous dosage forms but not for parenterals I. Advantages of Solutions  Easier to swallow – children, elderly, intensive care pts.  More quickly effective than tablets and capsules  Homogenous – give uniform dose than suspension or emulsion (w/ shaking)  Flexible dosing is possible  Dilute irritant action of some drugs (aspirin, KCl, KBr)  minimize ADEs in the GIT GASTROINTESTINAL TRACT ANTIBODY-DEPENDENT ENHANCEMENT ? I. Disadvantages of Solutions  Bulky  Unpleasant taste or odors are difficult to mask.  Needs an accurate spoon to measure the dose.  Less stable than solid dosage forms. Major signs of instability:  Color change  Precipitation  Microbial growth  Chemical gas formation Stability of Solutions A solution must retain its: 3  Clarity,  Color,  Odor and taste,  Viscosity over its shelf life  1. BUFFERS II. Additives:. 2 ISOTONICITY MODIFIERS. 3 VISCOSITY ENHANCEMENT 1. Buffers 4. PRESERVATIVES 2. Isotonicity modifiers  Solutions for injection  Application to mucous membrane  Large-volume solutions for ophthalmic application  Most widely used isotonicity modifiers:  Dextrose, NaCl = opTHALMic LARGE-VOLUME  on Additives: Il ↓ conc.) + 3. Viscosity enhancement  For aqueous-based topical solutions to remain on the skin or in the eye.  Low concentrations of jelling agents are added. 4. Preservatives  Solution may be contaminated  Sources of contamination:  Raw materials  Equipment, Environment and Personnel  Consumer use Additives: Preservatives used should be:  Effective against a wide spectrum of microorganisms  Stable for its shelf life  Non toxic, non sensitizing  Compatible with the ingredients in the dosage form  Free of taste and odor PRESERVATIVES ↳ ALCOMOLS DIQUATERNARY Ammonium compounds Additives: 5) SWEETENING · ACIDS AGENTS ESTERS  Preservatives – used alone or in combination Starch enema-itself/ vehicle Alcohols water-solvent/compi preservatives alone/combi - 1. Ethanol  Useful as a preservative when it is used as a solvent.  Needs high concentration (>10%) to be effective 2. Propylene glycol  Used as a solvent in oral solutions and topical preparations.  As preservative – 15 to 30%  Not volatile like ethanol  ACIDS : Additives: · BENZOIC ACID - SORBIC ACID Acids: Benzoic acid and sorbic acid  Low solubility in water  Used in a concentration from 0.1 % to 0.5%  Its use is restricted to preparations with a pH below 4.5  Unionized form C4 5 PH. Additives: Esters: Parabens  Esters (methyl, ethyl, propyl, butyl) of p – hydroxybenzoic  Used widely in pharmaceutical products and are effective and stable over a pH range of 4 to 8.  Employed at concentrations up to about 0.2%.  Frequently 2 esters are used in combination:  To achieve a higher total concentration  To be active against a wider range of microorganisms. Additives: QAC : - BENZALKONIUM 21 0. 002 % -0 02 %. - ANTIOXIDANTS Quaternary Ammonium Compounds: Benzalkonium chloride  Used at ow concentration 0.002 to 0.02%.  Has an optimal activity over the pH 4 to 10.  Quite stable at most temperatures. Unionized - $4. 5 pl (BASSA) Parabens - 4 to 8 pH Benealkoniume. 4 to 10 pH Additives: Antioxidants  Vitamins, essential oils & almost all fats and oils can be oxidized.  Oxidation reaction can be initiated by:  Heat  Light  Heavy metals (e.g. Fe, Cu) Minimized by using:  Sequestering agents – citric acid or ethylenediamine tetraacetic acid (EDTA)  Antioxidants – propyl & octyl esters of gallic acid, tocopherols (Vit. E), sodium sulfite, ascorbic acid (Vit. C)  SWEETENING AGENTS : Additives: - SUCROSE POLYHYDRIC ALCOHOLS - Sweetening agents 1. Sucrose  Most widely used sweetening agent.  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. BABSA $4 5 PH -. Paranens 4 to SpH 2. Polyhydric alcohols SM - Bene alkonium cl - 4 to 10pH  Sorbitol, mannitol and glycerol Sucrose - ↑4 to SpH  Can be used for diabetic preparations.  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. Sprays 6. Oleo Vitamin 7. Otic solutions 8. Inhalations Aqueous Solutions Aqueous solutions  Homogeneous mixtures prepared by dissolving a solid, liquid or gas in an aqueous medium (vehicle). Vehicle: AWE  water, aromatic water or extracts  1) Tap He cooled boiled Freshly 2) Water 3. ) He Purified Hed injection 4) Hyd for  Used both as vehicle and as a solvent for the desired flavoring or medicinal ingredients.  Advantages: Tasteless, odorless, lack of pharmacological activity, neutral and very cheap Tap Water  Not permitted to use for dispensing pharmaceutical dosage forms due to:  possible bacterial contamination  presence of dissolved salts that & destroy the active ingredients or& enhance their decomposition. Water Freshly Boiled and Cooled Water  Boiling is seldom used to destroy bacteria.  On storage for long time spores may yield microorganism. Purified Water  Must be used for most pharmaceutical operations and in all the tests and assays.  Prepared by distillation, deionization; reverse osmosis. Water Purified Water  Ultraviolet energy, heat or filtration (Millipore filtration) can be used to remove or kill the microorganisms present in water. TWO TYPES : "Hard" waters – contain Ca and Mg cations “Alkaline" water – contain bicarbonates (major impurity) Water for injection DILUTE PARENTERAL POWDERS  Must be used for the formulation of parental solutions. s  It is obtained by sterilizing pyrogen-free distilled water. FEVER-CAUSING MICROORGANISMS Aromatic Water Aromatic Waters (Medicated Waters)  Clear, saturated aqueous solution of volatile oils or other aromatic or volatile substances.  Used principally as flavored or perfumed vehicles.  Volatile oils solutions represent an incompatibility problem of salting out  occurs after the incorporation of a very soluble salt in their solution. Aromatic Water ~ noT THAT STABLE · TALC CLARIFYING AGENT Aromatic water will deteriorate with time, thus:  Should be made in small quantities  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 mold growth. Methods in Preparing Aromatic Water Distillation  Advantage: Most satisfactory method  Disadvantage: Slow and expensive  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.  If the volatile principle in the water are present in small quantities – distillate is returned several times to the still with fresh portions of drug  Cohobation Methods in Preparing Aromatic Water Solution 1. Direct Solution 2. Alternate Solution  Prepared by shaking volatile substance with purified water.  Mixture is set aside for 12 hours & filtered.  Talc (inert)  Dispersing agent  Filtering aid Methods of Preparing Solution 1. Simple Solution  Heat  Use of solubilizing agent  Reduction of particle size  Vigorous agitation 2. Solution by Chemical Reaction 3. Solution by Extraction I. AQUEOUS SOLUTIONS LIQUID DOSAGE FORMS 1. Douches CAA  Aqueous solution directed against a part or into a cavity of the body.  It functions as a cleansing or antiseptic agent. E  Dispensed in the form of a powder with directions for dissolving in a specified quantity of water.  Packaged in bulk or as unit packages ⑮  EYE Douches PHARYUGEAL NASAL & VAGINAL Eye douches  Used to remove foreign particles and discharges from the eyes.  Directed gently at an oblique angle and is allowed to run from the inner to the outer corner of the eye. Pharyngeal douches  Used to prepare the interior of the throat for an operation and to cleanse it in supportive conditions. Nasal and vaginal douches Component of Douche Powders 1. Boric acid or sodium borate 2. Astringents (Potassium, alum, Ammonium alum, and Zinc sulfate) 3. Antimicrobials (Oxyquinoline sulfate and Povidone iodine) 4. Quaternary ammonium compounds (Benzethonium chloride) 5. Detergents (Sodium lauryl sulfate) SLS 6. Oxidizing agents (Sodium perborate) 7. Salts (Sodium citrate, Sodium chloride) 8. Aromatics (menthol, thymol, eucalyptol, methyl salicylate, phenol) CTABLE 11. 3 SA AUSEL'S MGA REFERENCE) 2. Enemas  Preparations for rectal injections employed to:  Evacuate the bowel (Evacuation enemas)  Influence the general system by absorption (Retention enemas) e.g. nutritive, sedative or stimulating properties.  Affect locally the site of disease  May contain radiopaque substances for roentgenographic examination of the lower bowel.  - RETENTION Enemas - STARCH Retention enemas  Used in small quantities (about 30 mL)  Called retention microenema Starch enema  May be used either by itself or as a vehicle for other forms of medication. Enema  Enema – Radiographic Examination BARIum SULFATE ENEma JEXAMPLE 3. Gargles  Aqueous solutions frequently containing antiseptics, antibiotics and/or anesthetics. O  Used for treating the pharynx (throat) and nasopharynx by forcing air from the lungs through the gargle, which is held in the throat  expectorated - spit/cough from throat  Many gargles must be diluted with water prior to use.  Should be labeled so that it cannot be mistaken for preparations intended for internal administration. Gargling 4. Mouthwashes  Can be used for therapeutic & cosmetic purposes Therapeutic mouthwashes  Formulated to reduce plaque, gingivitis, dental caries and stomatitis. Cosmetic mouthwashes  Formulated to reduce bad breath through the use of antimicrobial and/or flavoring agents. Mouthwashes Mouthwashes containing:  Combination of antihistamines, hydrocortisone, nystatin and tetracycline -- Stomatitis  Allopurinol – Stomatitis  Pilocarpine –Xerostoma (dry mouth)  Tranexamic acid – Prevention of bleeding (oral surgery)  Carbenoxolone – Orofacial herpes simplex infections  ALCOHOLS-SURFACTANTS - Mouthwashes - HUMECTANTS - FLAVORING AGENTS Generally contain four groups of excipients: 1. Alcohols (10-20% in MW)  May function as a preservative  Aids in masking the unpleasant taste of AIs  As a solubilizing agent for some flavoring agents 2. Humectants (5-20% in MW)  Glycerin and sorbitol  Increase the viscosity of the preparation  Enhance the sweetness of the product  Improve the preservative qualities of the product. Major Groups of Excipients: 3. Surfactants (0.1 – 0.5%)  Used as emulsifying agents  Aid in the solubilization of flavors  Aid in the removal of debris by providing foaming action DETERGENT  Anionic surfactant – Sodium lauryl sulfate  Cationic surfactant – Cetylpyridinium Chloride  Nonionic class – Polyoxyethylene/Polyoxypropylene block copolymers or polyoxyethylene derivatives of sorbitol fatty acid esters Mouthwashes 4. Flavoring agent  Used in conjunction with alcohol and humectants to overcome disagreeable tastes.  Principle flavoring agents:  Peppermint, cinnamon, menthol or methyl salicylate 5. CoIoring agents