Dosage - Chapter 13

7/30/2019 Dosage - Chapter 13

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Aira Jhamaica DimacalePharmaceutical DosageChapter 13: SolutionsSolutions Liquid preparations containing one or more chemical

substances dissolved in a suitable solvent or mixture ofmutually miscible solvents

Prepared from a combination of solid, liquid, and gas According to use: oral, otic, ophthalmic, or topical According to composition:

Syrups: aqueous solutions containing sugar Elixirs: sweetened hydroalcoholic solutions Spirits: solutions of aromatic materials Tinctures or fluid extracts: active constituents from

crude drugs Tincture: alcoholic or hydroalcoholic Injections: parenteral preparations (sterile and

pyrogen-free)

Preparations where the medicinal agents are intended toprovide systemic effects:

Oral solutions, syrups, elixirs, spirits and tinctures Absorption is rapid than suspension or

solid dosage forms of the same medicinalagent

Information utilized in formulation or compoundinga pharmaceutical solution:

Solubility and stability of solutes to thesolvent

Avoided in the formulation or compounding: Combination of medicinal or

pharmaceutical agents resulting inchemical or physical interactions affectingtherapeutic quality or stability

Solubility Attractive forces between atoms:

Lead to formulation of molecules and atoms Attractive forces between molecules:

Causes them to cohere Like dissolves like

Dipole-dipole or Vander Waals forces Associated with the weak reactions

Saturated solution When a solvent at a given temperature has dissolvedall of the solute

Increase in temperature (important factor) increases solubility Factors affecting solubility

Temperature, pressure and pH, particle size andextent of agitation

Positive heat of solution Chemicals absorb heat when they are dissolved

resulting in increased solubility with increasedtemperature

Negative heat of solution Decrease in solubility with a rise in temperature

Solubility expressed as grams of solute dissolving in mL ofsolvent (g/mL)

Kinds of Solutions Aqueous

Water-based, water as main solvent Non-aqueous

Not water but another solvent Hydroalcoholic: alcohol as main solvent

o Elixirs and spirits Oleaginous: oil as main solvent

o Liniment and toothache drops Ethereal: ether as the main solvent

o CollodionSolvent for Liquid Preparations Alcohol, USP: Ethyl Alcohol, ethanol (94.9 96.0% ethanol by

volume)

Most useful solvent next to water Hydroalcoholic mixture with water Miscible with water Dissolve other water-insoluble ingredients Used with other solvents: glycols and glycerin to

reduce the amount of alcohol required Antimicrobial preservative Toxic effects when ingested in pharmaceutica

products by children Recommended by the content for OTC drugs:

Under 6 yrs of age: 0.5% 6 to 12 yrs.: 5% Over 12 yrs -Adults: 10%

Diluted Alcohol, NF (49%) Produced by mixing equal amount of water and

alcohol Upon mixing the volume is 3% less because liquids

contract Hydroalcoholic solvent in pharmaceutical processes

and preparations Rubbing Alcohol (79% ethyl alcohol)

Other components: denaturants with or without coloradditives, perfume oils, and preservatives

Composed of 8 parts of volume of acetone, 1.5 partsof methyl iso-butyl ketone, and 100 parts of ethyalcohol

Denatorium benazoate is added to prevent accidentaor abusive ingestion

Use: rubefacient, soothing rub, germicide, skincleaner, vehicle

Synonym: alcohol rubbing component Glycerin, USP

Clear, syrupy liquid with a sweet taste Miscible with water and alcohol With its viscosity: solutes are slowly soluble Not mixed with oxidizing agents (KMnO4, KClO3)

will form an explosive combination Preservative, stabilizer and auxiliary solvent

internal preparations Isopropyl Rubbing Alcohol

70% by volume isopropyl alcohol and the remainder Denaturants with or without color additives

perfume oils and stabilizers

Rubefacient, soothing rub, vehicle, preparing needlesand syringes (diabetic patients) for hypodermicinjections of insulin and skin disinfectant

Propylene Glycol, USP Viscous liquid miscible with water and alcohol Useful solvent and substitute for glycerin

Solvent for Liquid Preparation Purified Water, USP

Naturally occurring water exerts solvent effecton most substance it contacts (impurecontaining amount of: Dissolved inorganic salts: Na, K, Ca, Mg

Fe, Cl, SO4, & HCO3 Dissolved and undissolved organic mater Microorganisms

Obtained by distillation, ion exchange, andreverse osmosis

Ion exchangeo Makes use of filter

membranes in removingcontaminants

o Advantages over distillationpermit ease of operationminimal maintenance, andmore mobile facility

Reverse Osmosiso Pressurized steam of water

is passed parallel to the


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inner side of a filtermembrane core

Preparation of Solution Most pharmaceutical preparation solutions

Unsaturated with solute The strengths of pharmaceutical preparations

Expressed in % strength For very dilute preparations ration strengths

Several techniques to hasten dissolution Applying heat Reducing the particle size of the solute Using a solubilizing agent Subject the ingredients to vigorous agitation

Solutions intended for oral administration contain Flavorants and colorants When needed:

Stabilizers of medicinal agents Preservative (prevents growth of

microorganisms)Oral Solutions and Preparation for Oral Solution

Dry mixtures for solution or reconstitution Number of medicinal agents (antibiotics) with

insufficient stability in aqueous solution to meetextent shelf-life periods

7-14 days: expiration date after filling with asuitable solventExample:

Cloxacilin Sodium for Oral Solution,USP

o Anti-infective Penicillin V Potassium for Oral

Solution, USPo Anti-infective

KCl for Oral Solution, USPo K Supplement

Oral solutions Pediatric form of an adult product Reconstituting a dry powder

mixture/extemporaneously compound an oralsolution from bulk components

Oral rehydration solutions Rapid fluid loss associated with diarrhea lead

to:

Dehydration Ultimately death in some patientsparticularly the infants

Effective in treatment of patients with mildvolume depletion 3 to 10% of body weight

OTC, inexpensive and use diminished theincidence of complications associated parentallyadministered electrolytes solution

Typical oral rehydration solution contains: 45 mEq Na, 20 mEq Cl, 30 mEq

Citrate and 25 g dextrose Never mixed with or given with other

electrolyte-containing liquids: Milk Fruits

Commercial oral electrolyte solution: Prevents dehydration or achieverehydration

Examples:o Pedialyte solutiono Rehydrate solution

Oral colonic lavage solution Administration of oral laxative:

Magnesium citrate or bisacodyl thenight before

Cleansing enema administered 2 to 4hours prior to the procedure

Alternative method to prepare thegastrointestinal tract:

Requires less time and dietaryrestriction and obviates cleansingenemas

Entails oral administration ofbalanced solution of electrolytes withPEG

Adult dose: 4L, 240 ml per 10 minutes until 4Lis achieved

Magnesium citrate oral solution Citrate or citrate of magnesia Colorless to slightly yellow clear effervescen

liquid, sweet acidulous taste and lemon flavor Excellent medium for the growth of molds and

any molds spores: must be killed to remainstable

Always been troublesome: Tendency to deposit a crystalline solid

upon standing Sodium citrate and citric acid oral solution

Contains sodium citrate 100 mg and citric acid67 mg in each millimeter of aqueous solution

Syrups Concentrated aqueous preparations of a sugar or sugar

substitute with or without flavoring agents and medicinasubstances

Serves as: Pleasant tasting vehicle for medicina

substances in: Extemporaneous compounding o

prescription Preparation of a standard formula for

a medicated syrup Commercially prepared medicated syrups:

By combining: Sucrose Purified water Flavoring Coloring agents The therapeutic agent Other ingredients

Clear aqueous saturated solution of sugar commonlysucrose

1.313: specific gravity 85%w/v or 65%w/w High osmotic pressure Maybe:

Medicated: with active ingredient Non-medicated

Components of Syrup Sucrose or sugar substitute

Provide sweetness and viscosity Antimicrobial preservatives Flavorants Colorants

Sucrose Based and Non-sucrose Based Syrups: Sucrose: sugar most frequently employed in syrups

Special circumstances: replaces by other sugarsubstances:

Sorbitol Glycerin Prophylene glycol

Replaced by nonglycogenetic substances Methylcellulose or hydroxyl ethylcellulose

Most syrups contain 60 to 80% sucrose Efficient nutrient medium for growth of microorganisms Concentrated sugar solution

Resistant to microbial growth Syrup NF 26 (Simple Syrup) prepared by:


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Dissolving 85g of sucrose in purified water tomake 100 ml of syrup

Antimicrobial Agent The amount of preservative

Varies with the proportion of water available forgrowth:

Benzoic acid: 0.1-0.2% Sodium Benzoate: 0.1-0.2% Methylparabens, proplyparabens and

butylparabens, totaling to 1%Flavorant

Synthetic flavorant or with naturally occurring materialssuch as volatile oils (e.g. orange oil), vanillin, and others

Colorant Enhance the appeal of the syrup Correlates with the flavorant employed

Method of Preparation of Syrups Solution of the ingredients with the aid of heat (fastest) Solution of the ingredients with agitation without the use

of heat, or the simple admixture of liquid components(slowest)

Addition of sucrose to a prepared medicated liquid or to aflavored liquid

Percolation of either the source of medicating substanceor of the sucrose

Solution with the Aid of Heat Sugar added to the purified water and heat is applied Syrup when overheated

Becomes amber colored as the sucrosecaramelizes

Excessive heating convert syrups into itinversion form(Excessive heat Inversion Caramelization)

Medicinal agents destroyed by elevated temperatureSolution by Agitation Without Aid of Heat

Dissolves with purified water Ingredients in a vessel larger than the volume o

syrup to be prepared permitting thoroughagitation of the mixture

Addition of Sucrose to a Medicated Liquid or to Flavored Liquid Alcohol-soluble components

Undesirable or unnecessary components ocorresponding syrup

Removed by mixing the tincture or fluid extracwith water

Table 13.5: Examples of Oral Solutions by Category

Oral Solution Representative CommercialProducts

Concentration of CommercialProduct

Comments

Nortriptyline HClPamelor Oral Solution

(Novartis)10mg nortriptyline/5ml Tricyclic antidepressant

Fluoxetine HCl Prozac Liquid (Dista) 20mg fluoxetine/5ml For depression, obsessive compulsive disorder

Diphenoxylate HCl,

atropine sulfateLomotil Liquid (Searle)

2.5mg diphenoxylate HCl, 0.025mg

atropine sulfate/5ml

For diarrhea. Diphenoxylate is relate

structurally and pharcologically to the opiomeperidine. Atropine sulfate in subtherapeut

amounts discourages (by virtue of side effect

deliberate overdosage

Loperamide HClImodium A-D Liquid (McNeil

Consumer Products)1mg loperamide HCl/5ml

For diarrhea in adults and children aged

years and older. Structurally related t

haloperidol.

Haloperidol Haloperidol Oral Solution 2mg haloperidol/ml Primarily for severe neuropsychiatr

conditions when oral medication is preferre

and tablets and capsules are impracticaConcenreted solutions used by adding desire

amount of concentrate bt calibrated dropper t

soup or a beverage.

Perphenazine Perphenazine Oral Solution 16mg perphenazine/5ml

Thiothixene HCl Navane concentrate (Pfizer)


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TheophyllineTheophylline Oral Solution

(Roxane)80mg theophylline/15ml

Alcohol-free solution for treatment of bronchi

asthma and reversible bronchospasm

associated with chronic bronchitis an

emphysema.

Magnesium Citrate,

USP

Magnesium citrate equivalent to

1.55-1.9 g/100ml magnesium oxideDiscussed in text.

Sodium phosphate Phospho-Soda (Fleet)2.4g monobasic sodium phosphate,

0.9g dibasic sodium phosphate/5ml

Prenisolone sodium

phosphate

Pediapred Oral Solution

(Medeva)

5mg prednisolone (as sodium

phosphate)/5ml

Synthetic adrenocortical steroid with main

glucocorticoid properties indicated fo

endocrine, rheumatic, collagen, allergic, an

other disorders.

Sodium fluoride Pediaflor Drops (Boss) 0.5 mg/ml

Prophylaxis of dental caries; for use whe

community water supply is inadequate

fluoridated.

Potassium chloride KaoChlor 10% Liquid (Adria)20 mEq KCl/15ml in flavored

aqueous vehicle

For hypopotassemia (low blood level

potassium). Condition may be prompted b

severe or chronic diarrhea, low dietary intak

of potassium, increased renal excretion

potassium, other causes. Solution is dilute

with water or fruit juice.

Docusate sodium Colace syrup (Shire) 10mg docusate sodium/ml

Usually 50-200mg measured by calibrate

dropper, mixed with milk, fruit juice, othe

liquid to mask taste. Softens fecal mass b

lowering surface tension, permitting norm

bowel habits, particularly in geriatri

pediatric cardiac, obstetric, and surgic

patients. Taken for several days or until bow

movements are normal.

Ferrous sulfateFer-In-Sol Drops (Mead

Johnson Nutritional)15mg/0.6ml

For prevention and treatment of iro

deficiency anemias. Usual propylactic dose 0

or 0.6ml, measured by calibrated droppe

mixed with water or juice. Dosage for intende

primarily for infants and children.


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Cimetidine HClTagamet HCl Liquid

(SmithKline Beecham)300mg/ml

For peptic ulcer disease, patholog

hypersecretory conditions, e.g

ZollingerEllison syndrome.

Methadone HCl Methadone HCl (Roxane) 1 or 2 mg/mlFor relief of severe pain; detoxification

maintenance treatment of opioid addiction.

Ergocalciferol Calciferol Drops (Schwarz) 8,000 U/ml

Water-insoluble ergocalciferol (vitamin D2) i

propylene glycol. Usual propylactic dose abou

400U; therapeutic dose may be as high a

200,000-500,000 U daily in treating rickets.

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Dosage - Chapter 13