Lecture 4-5 Pharmaceutics I PDF

 Pharmaceutical Solutions Sweet &/or Viscid Aqueous Nonaqueous Water Alcohols, Oils Sweet and viscous Contain sugars 1. Oral solutions Liquid paraffin Of special interest ethe...

 Pharmaceutical Solutions Sweet &/or Viscid Aqueous Nonaqueous Water Alcohols, Oils Sweet and viscous Contain sugars 1. Oral solutions Liquid paraffin Of special interest ether and/or gums 2. Douches 1. Elixirs 1. Syrups 3. Enemas 2. Spirits 2. Honeys 4. Gargles 3. Collodions 3. Mucilages 5. Mouthwashes 4. Glycerites 4. Jellies 6. Nasal solutions 5. Liniments 5. Juices 7. Otic solutions 6. Oleo Vitamins 8- Aromatic water  Syrup Concentrated aqueous preparations of a sugar or sugar substitute with or without flavoring agents and medicinal substances. Non medicated/flavored syrupscontain only flavoring agent but not medicinal substances. They serve as pleasant tasting vehicles for medicinal substances to be added in extemporaneous compounding of prescriptions or in preparation of a standard formula for a medicated syrup  Medicated syrups contains Syrup + a therapeutic agent 4 Medicated syrups are prepared from: a) Sugar (sucrose/sugar substitute) to provide sweetness and viscosity b) Purified water c) Flavoring agent d) Coloring agents e) Therapeutic agent f) Antimicrobial preservative g) Many syrups especially commercial contain special solvents such as alcohol, solubilizing agents, thickeners and stabilizers 5  In addition to sucrose, certain other polyols, such as glycerin or sorbitol, may be added to retard crystallization of sucrose or to increase the solubility of added ingredients.  Alcohol often is included as a preservative and also as a solvent for flavors; further resistance to microbial attack can be enhanced by incorporating antimicrobial agents. 11/10/2024 6  Advantages of syrups 1- Masking disagreeable taste of drugs (due to sweetness of sugar and the viscosity that it imparts which causes physical concealment of the taste) 2- Effective and easy to swallow by children and elderly (compared to solid dosage forms) 3- Favored among parents due to little or no alcohol content 4- The thick and sweet syrup has soothing effect on the irritated tissues of the throat in case of anti-tussive syrups 7 Disadvantages of syrups 1. Stability of therapeutic agent may be changed due to change in pH of syrup in presence of flavoring agent (acidic, neutral or slightly basic) 2- If the syrup was completely saturated with sucrose in cool storage some sucrose might crystallize from solution causing the solution to be much unsaturated and probably suitable for microbial growth Bacteria Sucrose ppted crystal 8 Sucrose and non sucrose based syrups Sucrose is the sugar most frequently employed in syrups, in some cases it may be replaced in whole or in part by other sugars such as dextrose (sucrose based syrups) or substances such as sorbitol, glycerin and propylene glycol (non sucrose based syrup) In some instances (diabetic patients/diet controlled) all glycogenetic substances (converted to glucose in the body) are replaced by nonglycogenetic substances such as methylcellulose or hydroxyethylcellulose (non sucrose based syrup)  Methylcellulose or Hydroxyethylcellulose are not hydrolyzed and absorbed into the blood stream, and their use results in an excellent syrup-like vehicle for medications intended for  use by diabetic patients and others whose diet must be controlled and restricted to nonglycogenetic substances.  Methylcellulose or Hydroxyethylcellulose + one or more artificial sweeteners  excellent mimic of a true syrup. 9  Most syrups contain a high proportion of sucrose (60- 80%) to impart desirable sweetness and viscosity and causes inherent stability in contrast to the unstable nature of the dilute sucrose solution which is an efficient nutrient medium for the growth of microorganisms esp. yeasts and molds 10  Simple syrup, NF Prepared by dissolving 85 grams of sucrose in purified water to make 100 ml, has specific gravity of 1.313 It requires no additional preservation if it is to be used soon, preservatives are added if the syrup is to be stored 11  Concentration of syrup approaches but not reach the saturation point, WHY? Why sucrose should be in the range of 60-80% If diluted If saturated microorganism grow crystallization of sucrose (Due to availability of the free occurs upon cooling. water required for the growth  separation of an amount of microorganisms) of sucrose so the amount in solution becomes less than its solubility at the storage temperature  syrup would then be very much unsaturated(diluted)  suitable for microbial growth.  Some ingredients used in syrup 1- Antimicrobial preservative -The amount of a preservative required to protect the syrup against microbial growth varies with the proportion of water available for growth (free water) -and the nature and preservative activity of some materials such as flavoring oil Preservatives used are benzoic acid (0.1-0.2%), sodium benozate (0.1-0.2%) and various combinations of methyl, propyl and butylparabens (totaling 0.1%) -Frequently alcohol is used in syrups to assist dissolving of alcohol soluble ingredients and preservative if reaches 15-20% 2- Flavorant Synthetic flavorants or with naturally occurring materials as volatile oils (ex. Orange oil), vanillin and others render the syrup pleasant tasting. They must possess sufficient water solubility 3- Colorant To enhance the appeal of the syrup, a coloring agent is used that correlates with the flavorants employed (green with mint, brown with chocolate) 13 14 15  Preparation of syrups Solution with aid of heat Percolation of sucrose Solution by agitation 16 a) Solution with heat: it is rapid method but not used for: Volatile substance (flavored substances). Substance injured by heat (Thermolabile)  The sucrose is added to the purified water or aqueous solution and heated until dissolved, then strained and sufficient purified water added to make the desired weight or volume Excessive heating in the preparation of syrup must be avoided WHY? to prevent inversion of sucrose this reaction is termed inversion because invert sugar (dextrose and levulose monosaccarhides) is formed. C12H22O11 + H2O → C6H12O6 + C6H12O6 Sucrose Dextrose Levulose 17 Invert sugar properties: More fermentable. Tend to darken in colour. Overheating cause carmelization (brown color) But decrease oxidation of other drugs (levulose formed is reducing sugar) Levulose formed is sweeter than sucrose. Inverted syrup: When added to syrup. 1-Prevent oxidation of drug. 2- Prevent crystallization of sucrose. 3- Sweeter taste N.B. Acacia Syrup is an example of syrup prepared by soln with heat and used as flavored vehicle. 18  SUCROSE SUBSTITUTES A- Dextrose based syrups: -Used in syrup containing acid to avoid the inversion and discoloration on using sucrose. -Contains 70% W/V dextrose. -Less viscous and less sweet than simple syrup. -Glycerin is used as preservative. B- Sorbitol – based syrup: Hexahydric alcohol made by hydrogenation of glucose. Used in conc of 70% W/W in water. Its advantages over sucrose. - Not cause dental caries. - Although glycogenic like sucrose( i.e converted into glucose in the body), however it is not absorbed rapidly so not cause hyperglycemia. - Not support mould growth. - Chemically stable & not affected by heat 19 b) Agitation without heat: To avoid heat induced inversion of sucrose Suitable for volatile and thermolabile substance. Sucrose + water in bottle of twice size (allow active agitation & dissolution) shake to dissolve Used for codeine phosphate syrup (cough syrup) 20 c) Percolation; Water bed of coarse syrup granular sucrose A piece of cotton is placed in the neck of the percolator to prevent the passage of undissolved sucrose Coarse crystalline sucrose must be used to avoid formation of compact mass through which the liquid can not pass. Syrup USP is an example of syrup prepared by percolation. 21  Artificial syrup (Non-Nutritive syrup) used for: 1- Diabetic patient 2- Persons regulating their sugar/caloric intake First they used glycerin & propylene glycol but they are glycogenic substances ( Converted to glucose in body) Sodium carboxymethyl cellulose 1.5% (↑viscosity) Compound sodium cyclamate solution 6% cyclamate Na Preservative q.s 0.6% saccharin Na Purified water q.s. 22  IMPORTANT NOTE -However, the cyclamate studies showed that the sweetener could produce cancer in animals and, as a result, this substance was removed from a wide variety of products. Similar studies have been carried out on saccharin. -Much research has been done to find a safe synthetic substitute for sucrose. As a result, Aspartame which is about 200 times sweeter than sucrose, is being used now in many commercial preparations as the sweetening agent. 23  Other sweet & viscid preparations 1- Honeys: They are thick liquid preparations used as a base or sweetening agent, and it is widely used now. 2- Mucilage: They are thick, viscid, adhesive liquids, produced by dispersing gum in water, or by extracting the mucilaginous substances from vegetable matter with water. Preservatives must be added to the mucilage to prevent its deterioration. It is used as suspending agents. In addition, a synthetic mucilages are present such as carboxymethyl cellulose. 3- Jellies: They are like mucilage, in that it prepared from gums but they differ in having a jelly-like consistency. Jelly contains a big portion of water, and it is formulated by mixing water with gum tragacanth , acacia, gelatin and others. Jelly used as lubricants or for medication e.g. ephedrine sulphate jelly.  Cases For Study CASE I A pharmacist noted during dispensing that an oral liquid preparation stored in an amber-colored bottle appeared cloudy on the shelf. What parameters should he check before he dispenses that preparation? CASE II During formulation development, a scientist noticed some crystals deposited at the bottom of the bottle of an oral liquid solution preparation after 3 days. What may be the possible reason for this phenomena? CASE III In an extemporaneous dispensing facility, simple syrup NF is kept prepared for a few days as a vehicle in which to dispense other medications. The day after the syrup was prepared, a pharmacist noticed that the syrup was brownish instead of being colorless. Should he dispense the medication in this syrup? 25 Pharmaceutics Case Study 26 27  Aromatic waters - They are clear aqueous solutions saturated with volatile oils or other aromatic or volatile substances such as orange oil/peppermint oil/camphor - They have the odor and tastes of the volatile substances from which they are prepared and are used for perfuming and flavoring 28 Aromatic waters can be categorized in two types as: 1.Simple aromatic waters: They contain purified water as a solvent but do not contain alcohol and are mainly used as vehicles e.g. Chloroform water. 2. Concentrated aromatic waters: They contain alcohol as solvent for the volatile constituents. Examples are Camphor Water BP & Concentrated Peppermint Water BP 29 Preparation methods of aromatic water: A-Distillation C- Alternate B- Solution Method Method Solution Method 30  A-Distillation: (steam distillation ) The drug is ground and mixed with sufficient quantity of purified H2O in the distillation unit. It is slow and expensive but it is the most satisfactory method. COHOBATION: Itis the process in which the distillate is returned several times to the still with fresh portions of drug. This process is used when the volatile principle present in small quantities. Double distilled, triple distilled are used to describe the number of re-distillation “Strong rose water NF” is example of aromatic water prepared by distillation. 31  B- Solution Method 2 gm or 2 ml of the volatile substance Shake Filter, complete volume + 1000ml of purified to1000ml by purified water. Set aside for H2O 12 hrs. Aromatic water is prepared by shaking volatile substance with purified water. * The mixture is set aside for 12 hours to ensure saturation before it is filtered through wetted filter paper. A large excess of solute is used ( 2 gm per liter ) in order to obtain a saturated solution. Disadvantages (difficulties in the solution method) (1) Clarification (2) Time-consuming (12 hrs) “Chloroform water” is example of aromatic water prepared by solution process. 32  C- Alternate Solution process Used for the preparation of Peppermint water (using Talc): Mix 1.5 ml peppermint oil with 15 gm talc. Add purified water (1000ml) and agitate for 10 min. Filter through wet filter paper. Role of talc: (1) Increases the surface area of volatile substance to ensure rapid saturation of water (distributing agent/time saving). (2) Act as filter bed producing clear solution (Clarification and filter aid). Disadvantages of aromatic water: Deteriorate easily due to volatilization, decomposition or mould growth (should be made in small quantities and protected from light and heat by storing in air tight and light resistant containers in a cool place). If soluble salt is added, it causes salting out of the oil (incompatibility) (to solve this problem part of aromatic water is replaced by purified water). If they become cloudy they should be discarded no preservatives are allowed to be added. N.B.: natural volatile oil is now replaced by synthetic one e.g Imitation Otto Rose (contains Phenyl ethyl alcohol , Rhodinol) 34 35 1- Mouthwashes Mouthwashes can be used for therapeutic & cosmetic purposes (I) Therapeutic Mouthwashes can be formulated to reduce plaque, gingivitis, dental caries and stomatitis. e.g. a) Mouthwashes containing combination of hydrocortisone, nystatin and tetracycline have been prepared for the treatment of stomatitis, a painful side effect of cancer therapy. b) Tranexamic acid for the prevention of bleeding after oral surgery c) Anti- infective agent (e.g., hexitidine). (II) Cosmetic Mouthwashes may be formulated to reduce bad breath through the use of antimicrobial and/or flavoring agents. used to clean and refresh the buccal cavity Mouthwashes generally contain five groups of excipients 1)Flavors: are used in conjunction with alcohol and humectants to overcome disagreeable tastes. The principle flavoring agents are peppermint, cinnamon, menthol or methyl salicylate. 2) Humectants: such as glycerin and sorbitol increase the viscosity of the preparation enhance the sweetness of the product improve the preservative qualities of the product. 3) Surfactants: aid in the solubilization of flavors and in the removal of debris by providing foaming action. 4) AIcohols:  may function as a preservative.  aids in masking the unpleasant taste of active ingredients,  functions as a solubilizing agent for some flavoring agents 5) CoIouring agents: (e.g., amaranth) 38  3- Gargles - Gargles are aqueous solutions used for treating the pharynx (throat) and nasopharynx mild infections (soreness in mild throat infections) by forcing air from the lungs through the gargle, which is held in the throat; subsequently, the gargle is expectorated. - Frequently containing antiseptics, antibiotics and/or anesthetics for antiseptic, astringent and soothing effects - Many gargles must be diluted with water prior to use (Also Mouth washes). Example: - Phenol Gargle: contains phenol, glycerin, amaranth solution in water. Betadine Gargle/ MW 40  4- Enemas - They are rectal injection that are introduced into rectum, types: (I) Evacuation enemas: used to evacuate stool in constipation or before surgery. They act by stimulating peristalsis (may reach 400 ml) Eg: Evacuant soap enema BPC: is composed of 5% soft soap. marketed as single- dose- disposable unit. (II) Therapeutic (retention) enemas: may contain medicaments required to exert a local effect in the large bowel (e.g., anthelmintic enemas or Sulphamerazine rectal enema for the treatment of ulcerative colitis) (about 30ml). It is also referred to as Microenema (III) Diagnostic enemas: They contain radioopaque substances for X- ray diagnostic investigation in the large bowel (e.g., Barium sulfate enema that contain barium sulfate, acacia mucilage and starch enema may be used either by itself or as a vehicle for other forms of medication Therapeutic enema Barium Sulphate Enema (Diagnostic) Rx BARIUM SULPHATE 12 g. MUILAGE OF ACACIA 10 ml STARCH ENEMA ad 50 ml 42 5- Douches - Douche is an aqueous solution, which is directed against a part or into a cavity of the body by using bulb syringe, to cleanse, deodorize, soothe or medicate wounds, body orifices or cavities. It functions as a Cleansing, Antiseptic agent, astringent or promote healing. - Douches are most frequently dispensed in the form of: (1) A powder with directions for dissolving in a specified quantity of water (usually warm). (2) Tablets for preparing solutions are available. If powders or tablets are supplied, they must be free from insoluble material, in order to produce a clear solution. (3) Solutions form (1) An eye douche: used to remove foreign particles and discharges from the eyes. It is directed gently at an oblique angle and is allowed to run from the inner to the outer corner of the eye. (2) Pharyngeal douches: are used to prepare the interior of the throat for an operation and to cleanse it in supportive conditions e.g., Compound Sodium Borate Solution is used as pharyngeal or nasal douche. (1) Vaginal douches (Irrigations): These solutions may have an antiseptic, astringent, or soothing action e.g. Betadine Douche - Preparations of this type may contain: (1) Antiseptic/Antifungal (e.g., benzalkonium chloride, boric acid). (2) Astringent (e.g., zinc sulfate, alum). (3) Anesthetics (e.g., menthol). (4) Ingredients that change pH (e.g. sodium bicarbonate, citric acid) 6- Nasal Solutions - Nasal solutions are usually aqueous solutions designed to be administered to the nasal mucosa in small volume in Drops or Sprays. - Some drugs are administered through the nose for: their local effect to reduce nasal congestion and irritation (Eg: Ephedrine Sulfate Nasal Solution USP used as decongestant and drops containing chlorpheniramine maleate (antihistaminic), their systemic effect for administration of insulin and other hormones which are inactivated when administered orally. - Nasal decongestant solutions as drops or sprays are employed in the treatment of Rhinitis of the Common cold and for Allergic Rhinitis (hay fever) and for Sinusitis. - They are usually formulated to be isotonic with nasal secretions and buffered as nasal secretions (pH of 5.5 to 6.5) in order to minimize damage of nasal cilia, so that normal ciliary action is maintained  Nasal drops Proper administration of nasal drops/sprays 1- To minimize contamination the nasal product should be used by only one person 2- Prior to administration, the patient should blow the nose to clear the nostrils 3- With the drops, the patient should lie down on a flat surface, while tilting his head back to achieve maximum penetration, with sprays, the patient shouldn’t lie on a flat surface, only slight head tilting is required 4- The patient should preferably use the decongestant drops and spray for not more than 5 days to avoid rebound congestion Otrivin Nasal Spray 47  7- Otic (Aural)Solutions - They are simple solutions of medicaments designed to exert a local effect in the ear, to soften wax, to treat local inflammation and infections, or to relieve pain. - The main classes of drugs used for topical administration to the ear include Local anesthetics, e.g.: benzocaine; Antibiotics e.g.; neomycin; and Anti-inflammatory agents, e.g.; cortisone. - These preparations include the main types of solvents used, namely glycerin or water. The viscous glycerin permits the drug to remain in the ear for a long time. Anhydrous glycerin, being hygroscopic, tends to remove moisture from surrounding tissues, thus reducing swelling. - Viscous liquids like glycerin or propylene glycol either are used alone or in combination with a surfactant to aid in the removal of cerumen (ear wax). - In order to provide sufficient time for aqueous preparations to act, it is necessary for the patient to remain on his side for a few minutes so the drops do not run out of the ear. Otic Solutions For a Middle Ear Infection: While the person receiving Otic solution lies on his/her side, the person giving the drops should gently press the (TRAGUS) 4 times in a pumping motion. This will allow the drops to pass through the hole or tube in the eardrum and into the middle ear (made by the physician ) For an Ear Canal Infection While the person receiving the medication lies on his/her side, the person giving the drops should gently pull the outer ear upward and backward. This will allow the ear drops to flow down into the ear canal.  CERUMENEX Eardrops CERUMENEX Eardrops contain triethanolamine Polypeptide Oleate- Condensate (10%). Inactive Ingredients: Chlorobutanol 0.5%, Propylene Glycol and Water. Triethanolamine Polypeptide Oleate is a hygroscopic-miscible solution with low surface tension and optimal viscosity of 50-90 cps. It also has a slightly acid pH range (5.0-6.0) to approximate the surface of a normal ear canal. CERUMENEX Eardrops emulsify and disperse excess or impacted earwax. The triethanolamine polypeptide oleate, a surfactant, in a hygroscopic vehicle lyses cerumen to facilitate removal by subsequent water irrigation. 50  Topical solutions 1. Calcium hydroxide topical solution (lime water):- - Used as astringent, and as protective in several types of lotions 2. Lugols’ solution (Strong Iodine soln) - Used as germicidal 3. Povidone iodine topical solution: - A chemical complex of iodine with polyvinylpyrrolidone (PVP). - PVP is a polymer having an average molecular weight of about 40,000. The povidone iodine complex contains approximately 10% available iodine and slowly releases it when applied to the skin. - The preparation is employed topically as a surgical scrub and nonirritating antiseptic solution. - Commercial product: Betadine Solution 51 4. HYDROGEN PEROXIDE TOPICAL SOLUTION It contains 2.5% to 3.5% (w/v) hydrogen peroxide, or H2O2. Method of preparation: One method of preparation uses the action of either phosphoric or sulfuric acid on barium peroxide: BaO2 +H2SO4 BaSO4 + H2O2 The solution is a clear, colorless liquid. It usually deteriorates upon long standing, forming oxygen and water. Preservative agents, such as acetanilide, have been found to retard decomposition. Decomposition is enhanced by light and by heat, and for this reason, the solution should be preserved in tight, light-resistant containers, preferably at a temperature not exceeding 35°C (95°F). 52  Examples of pharmaceutically important topical solutions Hydrogen peroxide topical solution -It contains 2.5-3.5% w/v hydrogen peroxide. A solution of 30% hydrogen peroxide is capable of liberating 100 times its volume of oxygen -Used as local anti-infective for topical use on skin and mucous membranes. Its germicidal effect is based on the release of oxygen in contact with tissues 5- Coal tar topical solution -It is a solution containing 20% coal tar and 5% polysorbate 80 -It is used as for treatment of eczema 53 Thank you 54