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Solution dosage form Lecture 3. Oral solutions Dry mixtures for solution - Certain antibiotics have insufficient stability in aqueous solution to meet.

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Presentation on theme: "Solution dosage form Lecture 3. Oral solutions Dry mixtures for solution - Certain antibiotics have insufficient stability in aqueous solution to meet."— Presentation transcript:

1 Solution dosage form Lecture 3

2 Oral solutions Dry mixtures for solution - Certain antibiotics have insufficient stability in aqueous solution to meet extended shelf life periods. - They are provided in dry powders or granules for reconstitution with a prescribed amount of purified water immediately before dispensing to the patient. - - Once reconstituted, the solution remain stable in the refrigerator for the labeled period usually 7-14 days depending on the preparation. Examples: Penicillin V Potasium for oral solution, USP Cloxacillin Sodium for oral solution, USP Cloxacillin Sodium for oral solution, USP

3 Oral rehydration solutions Are usually effective in treatment of diarrhea and mild volume depletion (5-10% of body weight). These are available OTC A liter of typical oral rehydration solution contains: 45mEq Na +, 20 mEq K +, 35 mEq CL -, 30 mEq citrate, 25 g dextrose. These formulations are available in liquid or powder packets form for reconstitution These products should not be mixed with milk or fruit juice Oral colonic lavage solution Used for preparation of the bowel for colonoscopy, administration of a clear liquid diet for 24 to 48 hours preceding the procedure, administration of an oral laxative such as magnesium citrate the night before, and a cleansing enema administered 2 to 4 hours prior to the procedure. Used for preparation of the bowel for colonoscopy, administration of a clear liquid diet for 24 to 48 hours preceding the procedure, administration of an oral laxative such as magnesium citrate the night before, and a cleansing enema administered 2 to 4 hours prior to the procedure. Oral administration of a balanced electrolytes with PEG Oral administration of a balanced electrolytes with PEG Before dispensing it to the patient, the solution is reconstituted with water, creating an iso-osmotic solution having a mildy salty taste. PEG is an osmotic agent in the GIT Before dispensing it to the patient, the solution is reconstituted with water, creating an iso-osmotic solution having a mildy salty taste. PEG is an osmotic agent in the GIT The formulation is as follows: The formulation is as follows: PEG-3350; Sodium sulfate; sodium bicarbonate; sodium chloride; potassium chloride 240 ml every 10 min (total 4 L). PEG-3350; Sodium sulfate; sodium bicarbonate; sodium chloride; potassium chloride 240 ml every 10 min (total 4 L).

4 Syrups Syrups are concentrated solutions of sugar such as sucrose in water or other aqueous liquid. simple syrup: when water is used alone for making syrup. medicated syrup: when the aqueous preparation contains some added medicinal substance flavored syrup: which contains aromatic or pleasantly flavored substances and is intended to be used as a vehicle or flavor for prescriptions

5 Syrups Syrups are concentrated aqueous preparations of a sugar substitute with or without flavoring agents and medicinal substances. Syrups containing flavoring agents but not medicinal substances are called nonmedicated or flavored vehicles (syrups) such as cherry syrup, orange syrup and Raspberry syrup. These syrups are intended to serve as pleasant-tasting vehicles for medicinal substances. Medicinal syrups are commercially prepared from the starting materials, that is by combining each of the individual components of the syrup, such as sucrose, purified water, flavoring agents, coloring agents, the therapeutic agent, and other necessary and described ingredients. Naturally, medicated syrups are employed in therapeutics for the value of the medicinal agent present in the syrup. Components of syrups The sugar, usually sucrose or sugar substitute used to provide sweetness and viscosity. Antimicrobial preservatives Flavorants and colorants Also, many syrups contain special solvents, solubilizing agents, thickeners or stabilizer.

6 - Sucrose is the sugar most frequently employed in syrups it may be replaced by other sugars or substances such as sorbitol, glycerin and propylene glycol. - In some instances, all glycogenetic substances (materials converted to glucose in the body) are replaced by nonglycogenetic substances such as methylcellulose or hydroxy ethylcellulose. These two materials are not hydrolyzed and absorbed into the blood stream, and their use results in excellent syruplike vehicle for medications intended for use by diabetic patients. - - Most syrups contain a high proportion of sucrose, usually 60 to 80% not only because of the desirable sweetness and viscosity of such solutions but also because of their inherent stability in contrast to unstable character of dilute sucrose solutions. Additionally, the concentrated sugar solution are quite resistant to microbial growth. - Simple syrup Syrup, NF, is prepared by dissolving 85g of sucrose in enough purified water to make 100 ml of syrup. Syrup has a specific gravity of about The slight excess of water permits the syrup to remain physically stable in varying temperatures. If the syrup were completely saturated with sucrose, in cool storage some sucrose might crystallize from solution. As formulated, the official syrup is both stable and resistant to crystallization and microbial growth.

7 The amount of preservative required to protect a syrup against microbial growth varies with the proportion of water available for growth The amount of preservative required to protect a syrup against microbial growth varies with the proportion of water available for growth Preservative commonly used in syrups : benzoic acid %, sodium benzoate %, parabens (0.1%) Preservative commonly used in syrups : benzoic acid %, sodium benzoate %, parabens (0.1%) To enhance the appeal of the syrup, a coloring agent that correlates with the flavorant employed (green with mint, brown with chocolate). To enhance the appeal of the syrup, a coloring agent that correlates with the flavorant employed (green with mint, brown with chocolate). Most syrups are flavored with synthetic flavorants or with naturally occurring materials, such as volatile oils (orange oil), vanilin Most syrups are flavored with synthetic flavorants or with naturally occurring materials, such as volatile oils (orange oil), vanilin Colorant to enhance the appeal of the syrup may be added Colorant to enhance the appeal of the syrup may be added Sucrose-based syrup may be substituted by a polyol, such as sorbitol solution USP, 64% Sucrose-based syrup may be substituted by a polyol, such as sorbitol solution USP, 64% Examples of medicated syrup: Examples of medicated syrup: Analgesic Analgesic Anticholenergic Anticholenergic Antiemetics Antiemetics Anticonvulsant Anticonvulsant Antihistamine Antihistamine Antiviral Antiviral Antitussives Antitussives Expectrorant Expectrorant Bronchodilators Bronchodilators Fecal softener Fecal softener

8 Polyols (e.g. glycerin or sorbitol) may be added to - retard crystallization of sucrose or - increase the solubility of added ingredients. Alcohol often is included as - preservative - solvent for volatile oils. Syrups possess remarkable masking properties for bitter and saline drugs. It is important that the concentration of sucrose approaches but not quite reach the saturation point, WHY?  In dilute solutions sucrose provides an excellent nutrient for molds, yeasts, and other microorganisms.  In concentration of 65 % by weight or more the solution will retard the growth of such microorganisms (WHY?).  A saturated solution may lead to crystallization of a part of the sucrose under conditions of changing temperature.

9 When heat is used in the preparation of syrups, there is almost certain to be an inversion of a slight portion of the sucrose. C 12 H 22 O 11 2 C 6 H 12 O 6 Sucrose heat & acid Invert sugar (dextrose and levulose) The speed of inversion is greatly increased by acids (why ?); the hydrogen ion acts as a catalyst in this hydrolytic reaction. Invert sugar  is more readily fermentable than sucrose  tend to darken in color  retard the oxidation of other substances. The levulose formed during inversion is sweeter than sucrose; therefore the resulting syrup is sweeter than the original syrup. When syrup is overheated it caramelizes.

10 Invert Syrup:  It is prepared by hydrolyzing sucrose with hydrochloric acid and neutralizing the solution with Ca or Na carbonate.  The sucrose in the 66.7% w/w solution must be at least 95% inverted.  The invert syrup, when mixed in suitable proportions with syrup, prevents the deposition of crystals of sucrose under most conditions of storage.

11 Invert Syrup:  It is prepared by hydrolyzing sucrose with hydrochloric acid and neutralizing the solution with Ca or Na carbonate.  The sucrose in the 66.7% w/w solution must be at least 95% inverted.  The invert syrup, when mixed in suitable proportions with syrup, prevents the deposition of crystals of sucrose under most conditions of storage.

12 Preparation of Simple Syrup (a) Solution with heat  This is the usual method of making syrups:  in the absence of volatile agents or those injured by heat  when it is desirable to make the syrup rapidly.  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 syrups must be avoided to prevent inversion of sucrose, with increased tendency to fermentation. Syrups cannot be sterilized by autoclaving without caramelization (yellow color).  The specific gravity of syrup is an important property to identify its concentration. Syrup has a specific gravity of about 1.313, which means that each 100 ml of syrup weighs 1313 g.

13 (b) Agitation without Heat  This process is used in those cases where heat would cause loss of valuable volatile constituents.  The syrup is prepared by adding sucrose to the aqueous solution in a bottle of about twice the size required for the syrup. This permits active agitation and rapid solution.  The stoppering of the bottle is important, as it prevents contamination and loss during the process.

14 (c) Addition of a Medicating Liquid to syrup  This method is resorted to in those cases in which fluid extracts, tinctures, or other liquids are added to syrup to medicate it.  Syrups made in this way usually develop precipitates since alcohol is often an ingredient of the liquids thus used and the resinous and oily substances dissolved by the alcohol precipitate when mixed with syrup.  A modification of this process consists of mixing the fluid extract or tincture with the water, allowing the mixture to stand to permit the separation of insoluble constituents, filtering & and then dissolving the sucrose in the filtrate.  This procedure is not permissible when the precipitated ingredients are the valuable medicinal agents.

15 (d) Percolation  In this procedure, purified water or an aqueous solution is permitted to pass slowly through a bed of crystalline sucrose, thus dissolving it and forming a syrup a pledget of cotton is placed in the neck of the percolator  If necessary, a portion of the liquid is repassed through the percolator to dissolve all of the sucrose. This method is used for the preparation of Syrup USP.

16 Preservation of Syrups  The USP suggests that syrups be kept at a temperature not above 25°C.  Preservatives such as glycerin, methyl paraben, benzoic acid and sodium benzoate may be added to prevent bacterial and mold growth, particularly when the concentration of sucrose in the syrup is low.  The concentration of preservative is proportional to the free water.  The official syrups should be preserved in well dried bottles and stored in a cool dark place.

17 Dextrose-Based Syrups  Dextrose may be used as a substitute for sucrose (WHEN?) in syrups containing strong acids in order to eliminate the discoloration associated with inversion.  Dextrose forms a saturated solution in water at 70% w/v, which is less viscous than simple syrup.  It dissolves more slowly than sucrose and is less sweet Preservatives are required to improve the keeping qualities of such syrups. Glycerin is added in 30% to 45% v/v as preservative.

18 Artificial Syrups (Non-Nutritive Syrups)  intended as substitutes for syrups and are to be administered to persons who must regulate their sugar and/or calorie intake accurately. e.g. persons suffering from diabetes mellitus.  Some early formulae included glycerin, however, glycerin and propylene glycol are glycogenetic substances, i.e. they are materials which are converted into glucose in the body.  An example of non–nutritive syrup is “Diabetic Simple Syrup”. It contains compound sodium cyclamate (6% cyclamate sodium and 0.6% saccharin sodium) 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.

19 Sorbitol-Based Syrups  Sorbitol which is hexahydric alcohol made by hydrogenation of glucose has been used in the preparation of syrup.  It is used mostly in the form of a 70% w/w aqueous solution.  Sorbitol solution is not irritating to the membrane of the mouth and throat and does not contribute to the formation of dental carries.  Sorbitol is metabolized and converted to glucose; however, it is not rapidly absorbed from the GlT as sugars. No significant hyperglycemia has been found (WHY?); it may be used as component of non-nutritive vehicles.  Sorbitol solution does not support mold growth. Preservative should be used in solution containing less than 60% w/w sorbitol.  It is chemically stable and inert with respect to drugs and other ingredients used in pharmaceutical perpetration.

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21 Advantages  If the drug is not completely soluble or unstable in aqueous medium it may be necessary to use an alternative non-aqueous solvent.  Oily solutions of drugs are often used for depot therapy e.g. in muscles It is essential to test: toxicity – irritancy – flammability – cost – stability and compatibility of solvents to avoid problems  Solvents such as acetone, benzene and petroleum ether are not used for internal products.  Internal products may contain ethanol, glycerol, propylene glycol certain oils.  For parental products the choice is very limited

22 This section is devoted to four groups of non-aqueous solutions: 1. alcoholic or hydroalcoholic solutions, e.g. elixirs and spirits, 2. ethereal solutions, e.g. the collodions 3. glycerin solutions, e.g. the glycerites, 4. oleaginous soIutions e.g. the liniments, medicated oils, oleo- vitamins, sprays, and toothache drops.

23 ELIXIRS  Are clear, pleasantly flavored, sweetened hydroalcoholic liquids intended for oral use and usually flavored to enhance their palatability.  They are used as flavors and vehicles e.g. Dexamethasone Elixir USP and Phenobarbital Elixir USP.  The main ingredients in elixirs are ethanol and water but glycerin, sorbitol, propylene glycol, flavoring agents, preservatives, and syrups are often used in the preparation of the final product.  EIixirs contain ethyl alcohol, however, the alcoholic content will vary greatly, from elixir containing only a small quantity to those that contain a considerable portion as a necessary aid to solubility  An elixir may contain water and alcohol soluble ingredients.

24 Elixirs Compared with syrups, elixirs are usually less sweet and less viscous because they contain a lower proportion of sugar and consequently are less effective than syrups in masking the taste of medicinal substances. Non-medicated elixirs are employed as vehicles. Non-medicated elixirs are employed as vehicles. In addition to alcohol and water, other solvents, such as glycerol and propylene glycol are frequently employed in elixirs as adjunctive solvents. In addition to alcohol and water, other solvents, such as glycerol and propylene glycol are frequently employed in elixirs as adjunctive solvents.

25 Elixirs are sweetened with sucrose, sorbitol, glycerol, and/or artificial sweeteners Elixirs are sweetened with sucrose, sorbitol, glycerol, and/or artificial sweeteners Elixirs having a high alcoholic content usually use artificial sweetener such as saccharin. Elixirs having a high alcoholic content usually use artificial sweetener such as saccharin. Most elixirs have coloring agents to enhance their appearance Most elixirs have coloring agents to enhance their appearance Elixirs containing more than 10-12% alcohol are usually self- preserving Elixirs containing more than 10-12% alcohol are usually self- preserving Because of their usual content of volatile oils and alcohol, elixirs should be stored in tight, light-resistant containers and protected from excessive heat Because of their usual content of volatile oils and alcohol, elixirs should be stored in tight, light-resistant containers and protected from excessive heat Antihistamine Elixir: Diphenhydramine HCl Antihistamine Elixir: Diphenhydramine HCl Analgesic Elixir: acetominophen Analgesic Elixir: acetominophen Cardiotonic Elixir: digoxin Cardiotonic Elixir: digoxin Antispasmodic Elixir: hyoscyamine sulfate Antispasmodic Elixir: hyoscyamine sulfate Sedative Elixir: phenobarbital Sedative Elixir: phenobarbital

26 Tinctures In medicine, a tincture is an alcoholic extract (e.g. of leaves or other plant material) or solution of a non-volatile substance; e.g. of iodine, mercurochrome). In medicine, a tincture is an alcoholic extract (e.g. of leaves or other plant material) or solution of a non-volatile substance; e.g. of iodine, mercurochrome).medicinealcoholicextractsolutionvolatileiodine mercurochromemedicinealcoholicextractsolutionvolatileiodine mercurochrome Tinctures contain alcohol in amounts ranging from approx %. The alcohol content protects against microbial growth Tinctures contain alcohol in amounts ranging from approx %. The alcohol content protects against microbial growth Other solvent, such as glycerol, may be employed Other solvent, such as glycerol, may be employed Tincture must be tightly stopered and not exposed to excessive temperature Tincture must be tightly stopered and not exposed to excessive temperature

27 Many tinctures must be stored in light-resistant containers and protect from sunlight. Many tinctures must be stored in light-resistant containers and protect from sunlight. Some examples that were formerly common in medicine include: Some examples that were formerly common in medicine include: Tincture of Cannabis sativa Tincture of Benzoin Tincture of Benzoin Tincture of Benzoin Tincture of Benzoin Tincture of cantharides Tincture of cantharidescantharides Tincture of green soap (which contains also lavender) lavender Tincture of iodine Tincture of iodineTincture of iodineTincture of iodine Tincture of opium (laudanum) Tincture of opium (laudanum)opiumlaudanumopiumlaudanum Camphorated tincture of opium (paregoric) Camphorated tincture of opium (paregoric) Camphoratedparegoric Camphoratedparegoric

28 Tincture of iodine is often found in emergency survival kits, used both to disinfect wounds and to sanitize surface water for drinking. Tincture of iodine is often found in emergency survival kits, used both to disinfect wounds and to sanitize surface water for drinking. When an alcohol solution is not desirable, Lugol's iodine, an aqueous solution of iodine in potassium iodide solution, or povidone iodine (Betadine), a PVP solution, can be used. When an alcohol solution is not desirable, Lugol's iodine, an aqueous solution of iodine in potassium iodide solution, or povidone iodine (Betadine), a PVP solution, can be used.Lugol's iodinepotassium iodidepovidone iodineBetadinePVP solutionLugol's iodinepotassium iodidepovidone iodineBetadinePVP solution Other names for Lugol's solution are I 2 KI (Iodine- Potassium Iodide); Markodine, Strong solution (Systemic); Aqueous Iodine Solution BP. Other names for Lugol's solution are I 2 KI (Iodine- Potassium Iodide); Markodine, Strong solution (Systemic); Aqueous Iodine Solution BP.

29 Topical tinctures Topical tinctures Iodine Tincture Iodine Tincture It is a reddish-brown colour tincture It is a reddish-brown colour tincture It is prepared from 2% iodine crystal and 2.4% sodium iodide in a vehicle alcohol/water (44-50% alcohol) It is prepared from 2% iodine crystal and 2.4% sodium iodide in a vehicle alcohol/water (44-50% alcohol) It is a popular local anti-infective agent applied to the skin in general household first aid It is a popular local anti-infective agent applied to the skin in general household first aid Compound Benzoin tincture Compound Benzoin tincture It is prepared from 10% benzoin and lesser amounts of aloe, storax and tolu balsam It is prepared from 10% benzoin and lesser amounts of aloe, storax and tolu balsam The mixture is macerated in alcohol The mixture is macerated in alcohol It is used to protect and toughen skin in the treatment of bedsores, ulcers, cracked nipples, and fissures of the anus It is used to protect and toughen skin in the treatment of bedsores, ulcers, cracked nipples, and fissures of the anus Also used in treatment of venereal warts Also used in treatment of venereal warts It is also used as an inhalent for bronchitis and other respiratory conditions It is also used as an inhalent for bronchitis and other respiratory conditions It is best stored in tight, light-resistant containers It is best stored in tight, light-resistant containers

30 Thimerosal Tincture Thimerosal Tincture The vehicle is water, acetone and 50% alcohol The vehicle is water, acetone and 50% alcohol It must be manufactured and stored in glass or suitably resistant containers It must be manufactured and stored in glass or suitably resistant containers Ethylenediamine is used as stabilizer in the official solution and tincture Ethylenediamine is used as stabilizer in the official solution and tincture The commercial preparation is colored orange red, the colour defines the area of application The commercial preparation is colored orange red, the colour defines the area of application It is a commonly used household antiseptic for application to the skin abrasions and cuts and in preparation of patients for surgery It is a commonly used household antiseptic for application to the skin abrasions and cuts and in preparation of patients for surgery Green Soap tincture Green Soap tincture 65% of active constituent in alcohol 65% of active constituent in alcohol Also contains 2% lavender oil as perfume Also contains 2% lavender oil as perfume Used as detergent Used as detergent


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