Solutions - solution drug delivery system PDF

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solution drug delivery system...

Description

Solutions -

Prepared from any combination of solid, liquid, gas Liquid preparations that contain one or more chemical substances dissolve in a suitable solvent or mixture of mutually miscible solvents

Solubility Dipolar molecules frequently tend to align themselves with other dipolar molecules so that the negative pole of one molecule points towards the positive pole of the other Large group of molecules maybe associated with weak attractions (Van der Waals forces) Temperature is an important factor in determining the solubility of a drug and in preparing solutions The solubility of a pure chemical substance at a given temperature and pressure is constant The greater the agitation, the more unsaturated the solvent passes over the drug, and the faster the formation of solutions Relative terms of solubility Descriptive term Very soluble Freely soluble Soluble Sparingly soluble Slightly soluble Very slightly soluble Practically insoluble or insoluble

Part of solvent required for 1 part of solute 10,000

Like dissolves like ➢ Solvent having a chemical structure most similar to that of the intended solute will be most likely to dissolve it Some solvents for liquid preparations 1. Alcohol, USP: Ethyl Alcohol, Ethanol, C₂H₅OH - Most useful solvent in pharmacy next to water - Used as primary solvent for many organic compounds - Often preferred because of its miscibility with water and its ability to dissolve many water insoluble ingredients Under 6 y/o- 0.5% 6-12 y/o- 5% Over 12 y/o and adults – 10% 2. Dilute alcohol, NF

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Prepared by mixing equal volumes of Alcohol, USP and Purified water, USP Final volume is generally about 3% less than what would otherwise be expected Is a useful hydroalcoholic solvent in various pharmaceutical processes and preparation

3. Alcohol, Rubbing (alcohol rubbing compound) - Contains about 70% ethyl alcohol by volume, the remainder consisting of water, denaturants, with or without color additives and perfume oils and stabilizers - Volatile and flammable - Should be stored in tight container, remote from fire - Employed as rubefacient externally and soothing rub for bedridden patients - Germicide for instruments and skin cleanser prior to injection - Used as vehicle for topical preparations 4. -

Glycerin, USP (Glycerol), CH₂OH•CHOH•CH₂OH Clear syrupy liquid with a sweet taste Miscible with both water and alcohol Has a preservative property and is often used as a stabilizer and as an auxiliary solvent in conjuction with water or alcohol Used in many internal preparation

5. Isoprpyl Rubbing alcohol - 70% by volume isopropyl alcohol, the remainder consisting of water with or without color additives, stabilizers and perfume oils - Used externally as rubefacient and soothing rub and as a topical for topical products This preparation and commercially available 91% of isopropyl alcohol solution are commonly employed by diabetic patients in preparing needles and syringes for hypodermic injections of insulin and for disinfecting the skin 6. Propylene Glycol, USP, CH₃CH(OH)CH₂OH - Viscous liquid, miscible with water and alcohol - Useful solvent with a wide range of applications and is frequently substituted for glycerin in modern pharmaceutical formulations A. Oral solutions - They are categorized as liquid preparation intended for oral administration that contain one or more substances with or without flavoring, sweetening, or coloring agents, dissolved in water or cosolvent-water mixtures by US Pharmacopeia - Can contain certain polyols (sorbitol, glycerin) to inhibit crystallization and to modify solubility, taste, mouth feel, and other medical properties - More homogenous and easier to swallow than drugs in solid form - Bulkier dosage, degrade more rapidly, and are more likely to interact with constituents than those in the solid forms

1. Water is the most commonly used vehicle for drug solutions Seven types of water for the preparation of dosage forms: a. Purified Water USP - Water obtained from distillation, ion exchange, reverse osmosis, or other suitable treatment - Cannot contain more than 10 parts per million (ppm) of total solid - Should have a pH between 5 and 7 - Used in prescriptions and finished manufactured products except parenteral and ophthalmic products b. Water for injection, USP - Water obtained by distillation or by reverse osmosis - Conforms with the standards of purified water but is also free of pyrogen - Used for the preparation of parenteral solutions c. Sterile water for injection, USP - Sterilized and packaged in single dose containers of Type I and II glass The limitation for total solids depend on the size of the container d. Bacteriostatic water for injection, USP - Contains one or more suitable antimicrobial agents - Packaged in single or multiple dose containers of Type I and II glass These containers do not exceed 30ml in capacity e. Sterile water for inhalation, USP - Purified by distillation or by reverse osmosis and rendered sterile - Does not contain antimicrobial agents except when used in humidifiers or similar devices - Should not be used for parenteral administration or for other sterile dosage form f. Sterile water for irrigation, USP - Sterilized and suitably packaged - Does not contain antimicrobial agent or other added substance g. Sterile purified water, USP - Sterilized and suitably packaged - Does not contain antimicrobial agent - Not intended for use in parenterals 2. Oral drug solutions

Includes syrups, and elixirs as well as other less widely prescribed classic (galenical) formulations such as aromatic water, tinctures, fluid extracts and spirits a. Syrups - -Traditionally per oral solutions that contain high concentration of sucrose or other sugars - Include any other liquid dosage form prepared in a sweet, viscous vehicle, including per oral suspensions 1. Syrup NF (simple syrups) - Concentrated or nearly saturated aqueous solution of sugar (85%, 65% w/w) 2. Syrups have a low solvent capacity for water soluble drugs because the hydrogen bonding between sucrose and water is very strong - It can be difficult or impossible to dissolve a drug in syrup - The drug is often dissolved in a small quantity of water, and the flavoring syrup is added 3. The sucrose concentration of syrup plays a crucial role in the control of microbial growth. - Dilute sucrose solutions are excellent media for microorganisms - Syrup NF is a self-preserved solution with a minimal tendency to undergo crystallization - Has a specific gravity of about 1.313 Components of Syrup 1. Sugar ➢ Sucrose or sugar substitute used to provide sweetness and viscosity 2. Antimicrobial preservatives 3. Flavorants 4. Colorants Sucrose and Non Sucrose based Syrups Sucrose is the sugar most frequently employed in syrups May be replaced in whole or in part by other sugar or substances such as sorbitol, glycerin, propylene glycol -

Antimicrobial Flavorants -

Preservatives Benzoic acid 0.1-0.2% Sodium benzoate- 0.1-0.2% Methylparaben, propylparaben, butylparaben= 0.1% Synthetic flavorants or with naturally occurring materials such as volatile oils (orange oil), vanillin, Must be water soluble

Colorants -

Coloring agent with the flavorant employed (green with mint, brown with chocolate)

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Water soluble, non reactive with other syrup components and color stable at the pH range

Preparation of Syrups 1. Solution with the aid of heat ➢ Used when it is desired to prepare the syrup as quickly as possible and when the syrup’s components are not damaged or volatilized by heat ➢ Sugar is added to the purified water and heat is applied until the sugar is dissolved Becomes amber colored as the sucrose caramelizes when overheated Use of boiled purified water in the preparation of a syrup can enhance its permanency and the addition of preservative agents when permitted can protect it during its shelf life ➢ Must be stored in a tight container 2. Solution by Agitation without the Aid of Heat ➢ More time consuming than use of heat but the product is with maximum stability 3. Addition of Sucrose to a Medicated Liquid or to a Flavored Liquid ➢ Tincture or fluidextracts is employed as the source of medication in the preparation of a syrup Ex: lemon tincture 4. Percolation ➢ Either sucrose may be percolated to prepare the syrup or the source of the medicinal agent may be percolated to form an extractive Ex: ipecac syrup – prepared by adding glycerin, and syrup to an extractive of powdered ipecac obtained by percolation Ipecac – from dried rhizome and roots of Cephaelis ipecacuanha

b. Elixirs - Sweetened hydroalcoholic solutions intended for oral use and are usually flavored to enhance their palatability Non medicated- employed as vehicles (Aromatic elixir, compound benzaldehyde elixir, isoalcoholic elixir) Medicated- used for therapeutic effect of the medicinal substances they contain Adjunctive solvents- glycerin and propylene glycol Elixir containing 10%-12% of alcohol are usually self preserving - Less sweet and less viscous than syrups because they contain a lower portion of sugar - Less effective than syrups for masking taste

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Traditionally per oral solutions that contain alcohol as a cosolvent Alcohol content of elixirs has varied from 5%-40% Becomes turbid when moderately diluted with aqueous liquid Not the preferred vehicle for salts because alcohol accentuates saline taste • Aromatic elixir NF ➢ Prepared in part of syrup ➢ Contains 22% of alcohol

Iso- alcoholic elixir ➢ Combination of low-alcoholic elixir (8%-10%) and high alcoholic elixir (73%-78%) Stored in tight, light resistant containers and protected from excessive heat •

Advantage -

Flexibility and ease of administration to patients who have difficulty swallowing solid forms

Disadvantage -

Its alcoholic content

Preparation of Elixirs -

Prepared by simple solution with agitation Admixture of two or more liquid ingredients

Medicated elixirs a. b. -

Antihistamine elixirs For symptomatic relief of allergic disorders Barbiturate Sedative and Hypnotic Elixir Used to produce various degrees of central nervous system depression SE: drowsiness and lethargy 1. Phenobarbital elixir - Long acting barbiturate with 4-6 hours duration of action c. Digoxin elixir - Cardiotonic glycoside obtsined from the leaves of Digitalis lanata - White crystalline powder that is insoluble to water but soluble in dilute alcohol solutions B. Miscellaneous solutions 1. Aromatic water - Clear, saturated aqueous solutions of volatile oils - Used as pleasantly flavored vehicles for a water soluble drugs or as an aqueous phase in an emulsion or suspensions

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Large amount of water soluble drug is added to aromatic water , then an insoluble layer may form at the top (salting out) Molecules of water soluble drugs have more attraction for the solvent molecules of water than the oil Should be stored in a tight, light resistant bottles to reduce volatilization and degradation from sunlight

Methods of preparing Aromatic water a. Distillation ➢ Universal method but is not economical or practical to most products ➢ Only method for preparing strong rose water and orange flower water b. Solution method ➢ Volatile or aromatic substances is admixed with water , with or without the use of disperant (eg. Talc)

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2. Diluted acids Aqueous solutions prepared by diluting the corresponding concentrated acids with purified water The strength is generally expressed on the percent weight-to-volume (%w/v) basis Most have a strength of 10% w/v with the exception of diluted acid which is 6% w/v 3. Spirits (Essences) Alcoholic or hydroalcoholic solutions of volatile substances that contain 50%90% alcohol The high alcoholic content maintains the water insoluble volatile oils in solutions Oils separate when water is added ▪ Medicinal- aromatic ammonia spirit ▪ Flavoring agents- compound orange spirit, compound cardamom spirit Stored in tight containers to reduce loss by evaporation 4. Tinctures Alcoholic or hydroalcoholic solutions of chemicals or soluble constituents of vegetable drugs Alcohol content of official tinctures varies from 17%-21% for opium tincture and 78%- 80% for compound benzoin tincture Alcohol content protects against microbial growth and keeps alcohol-soluble extractives in solution

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Medicated tinctures (Paregoric, USP or camphorated tincture of opium) Most tinctures are prepared by an extraction process of maceration or percolation the selection of solvent, or menstruum, is based in the solubility of the active and inert constituents of the crude drug Glycerin may be added to the hydroalcoholic solvent to increase the solubility of the active constituent and reduce precipitation on storage Must be tightly stoppered and kept from excessive heat Must be stored in light resistant containers (undergo photochemical change when exposed to light)

Topical Solutions and Tinctures -

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Prepared by simple dissolving Ex: compound benzoin Tincture is prepared by maceration of the natural contents in the solvent 5. Sprays Aqueous or oleaginous solutions in the form of course droplets or as finely divided solids To be applied topically, most usually to the nasopharyngeal tract or to the skin 6. Fluid extracts Liquid extracts for vegetable drugs that contains alcohol as a solvent, preservative or both Prepared by percolation Sometimes called “ 100% tinctures) 7. Nasal, ophthalmic, otic and parenteral solutions

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8. Mouthwashes Used to cleanse the mouth or treat diseases of the oral mucous membrane Often contain alcohol or glycerin to aid in dissolving the volatile ingredients More often used cosmetically than therapeutically 9. Astringents Locally applied solutions that precipitate protein They reduce cell permeability without causing injury Cause constriction with wrinkling and blanching of the skin Can be used as anti perspirant a. Aluminum Acetate Topical Solution (Burow’s solution) Colorless and has a faint acetous odor and a sweetish, astringent taste Applied topically as an astringent wash or dressing after dilution with 10-40 parts of water

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b. Aluminum Subacetate Topical Solution (modified Burow’s Solution) Ratio of aluminum oxide to acetic acetic acid 1:2.35 c. Calcium hydroxide topical solution (limewater, Liquid calcis) Limewater Not less than 140mg of Ca(OH)₂ in each 100ml of solution Less soluble than in cold water and cool purified water is the solvent Should be stored in well-filled, tightly stoppered containers (to deter the absorption of CO₂ and be kept in cool place to maintain adequate concentration of dissolved solute) Catergorized as astringent d. Coal tar topical solution (liquor carbonis detergens; liquor picis carbonis; LCD) Alcoholic solution containing 20% coal tar and 5% polysorbate 80 Nearly black viscous liquid having a characteristic naphthalene-like odor and a sharp , burning taste A tar obtained as a byproduct during the destructive distillation of bituminous coal Slightly soluble in water and partially soluble in most organic solvents including alcohol Commercially available as Tween 80 Local antieczematic used in external treatment of chronic skin conditions after dilution with about 9 volumes of water or in combination with other agents 10. Antibacterial topical solution Kill bacteria when applied to the skin or mucous membrane in the proper strength and under appropriate condition a. Hydrogen peroxide topical solution (peroxide) 2.5-3.5% (w/v) hydrogen peroxide(H₂O₂) Clear, colorless liquid that may be odorless or has the odor of ozone Deteriorated upon standing forming O₂ and H₂O Should be preserved tight, light resistant containers, preferably at temperature not exceeding 35˚C Local anti infective for use topically on the skin and mucous membrane Has the ability to cleanse wound b. Chlorhexidine Gluconate Solution Broad spectrum antiseptic in clinical and veterinary medicine Its spectrum encompasses P. aeriginosa Used as a surgical scrub, hand wash, and skin wound and general skin cleanser at 4% concentration

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Most common side effect is the formation of an extrinsic yellow brown stain on the teeth and the tongue after a few days use

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c. Povidone iodine topical solution Chemical complex of of iodine with polyvinylpyrrolidone Contains approximately 10% available iodine and slowly releases it when applied to the skin Used as a surgical scrub and nonirritating antiseptic solution Commercial product: Betadine solution

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d. Thimerosol topical solution Water soluble organic mercurial antibacterial agent Used topically for its bacteriostatic and fungistatic properties Used mainly to disinfect skin and as an application to wounds and abrasions Used as preservatives Contains 0.1% thimerosal Affected by light and must be maintained in light resistant containers Commercial product: Merthiolate solution

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Vaginal and rectal solutions Components of douche powders: 1. Boric acid or sodium borate 2. Astringents e.g. potassium, alum, ammonium alum, zinc sulfate 3. Antimicrobials e.g. oxyquinoline sulfate, povidone sulfate 4. Quaternary ammonium compounds e.g. bensethonium chloride 5. Detergents e.g. sodium lauryl sulfate 6. Oxidizing agent e.g. sodium perborate 7. Salts e.g. sodium citrate, sodium chloride 8. Aromatics e.g. menthol, thymol, eucalyptol, methyl salicylate, phenol Douche powders are used for their hygienic effect Used against monilial and trichomonal infections Retention enemas - Local effects: hydrocortisone - Systemic effects: aminophylline - Ex: corticosteroid Evacuation enemas Rectal enemas are used to cleanse the bowel Available in disposable plastic squeeze bottles containing a premeasured amount of enema solution Topical Oral (Dental) Solutions a. Benzocaine

Topical anesthetic For temporary relief of pain, soreness, and irritation in the mouth associated with teething, orthodontic appliances, new or poorly fitting dentures, and canker sores Camphorated parachlorophenol - Dental anti infective - Eutectic liquid composed of 65% camphor and 35% parachlorophenol - Used in dentistry for sterilization of deep root canals Carbamide peroxide topical solution - Dental anti infective - Acts as chemomechanical cleansing and debriding agent Cetylpyridinium chloride solution and lozenges - Commercial counterparts contain 1:2000 w/v and 1:1500 w/v of Cetylpyridinium - Used as freshening mouth cleanser Erythrosine sodium topical solution and soluble tablets - Diagnostic aid (dental disclosing agent) - Applied to the teeth to reveal plaque left by inadequate brushing -

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Eugenol - Dental analgesics - Applied topically to dental cavities and dental protectives - Pale yellow liquid having an aromatic odor of clove and a spicy tase Lidocaine oral spray - Topical dental anesthetic Nystatic oral suspension - Antifungal Saliva substitutes- Electrolytes in carboxymethylcellulose base - For the relief of dry mouth and throat in xerostomia Sodium fluoride oral solution and tablet - Dental caries prophylactic Sodium fluoride and phosphoric acid gel and topical solution - Dental caries prophylactic - Gel and solution contain 1.23% of fluoride ion and 1% of phosphoric acid Triamcinolone acetonide dental paste - Topical anti inflammatory agent Zinc oxide- eugenol mixture: temporary filling mix

Nonaqueous solutions a. Liniments - Alcoholic or oleaginous solutions or emulsions of various medicinal substances intended to be rubbed on the skin

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Alcoholic or hydroalcoholic vehicle ➢ Useful when rubefacient, c...