Aira Jhamaica Dimacale Pharmaceutical Dosage Chapter 13: Solutions Solutions Liquid preparations containing one or more chemical substances dissolved in a suitable solvent solvent or mixture of mutually 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 to provide systemic effects: Oral solutions, syrups, elixirs, spirits and tinctures Absorption is rapid than suspension or solid dosage forms of the same medicinal agent Information utilized in formulation or compounding a pharmaceutical solution: Solubility and stability of solutes to the solvent Avoided in the formulation or compounding: compounding: Combination of medicinal or pharmaceutical agents resulting in chemical or physical interactions affecting therapeutic quality or stability Solubility Attractive forces between atoms: Lead to formulation formulation of molecules and atoms Attractive forces between molecules: molecules: Causes them to cohere
“Like dissolves like”
Dipole-dipole or Vander W aal’s forces Associated with the weak reactions Saturated solution When a solvent at a given temperature has dissolved all of the solute Increase in temperature (important factor) increases solubility Factors affecting solubility Temperature, pressure and pH, particle size and extent of agitation Positive heat of solution Chemicals absorb heat when they are dissolved resulting in increased solubility with increased temperature Negative heat of solution Decrease in solubility with a rise in temperature Solubility expressed as grams of solute dissolving in mL of solvent (g/mL) Kinds of Solutions Aqueous Water-based, water as main solvent Non-aqueous Not water but another solvent Hydroalcoholic: alcohol as main solvent Elixirs and spirits o Oleaginous: oil as main solvent solvent Liniment and toothache drops o Ethereal: ether as the main solvent o Collodion Solvent 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 preservative Toxic effects when ingested in pharmaceutical 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 color additives, perfume oils, and preservatives Composed of 8 parts of volume of acetone, 1.5 parts of methyl iso-butyl ketone, and 100 parts of ethyl alcohol Denatorium benazoate is added to prevent accidental or abusive ingestion Use: rubefacient, soothing rub, germicide, skin cleaner, 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 (KMnO 4, 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 needles and syringes (diabetic patients) for hypodermic injections 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 effect on most substance it contacts (impure) containing amount of: Dissolved inorganic salts: Na, K, Ca, Mg, Fe, Cl, SO4, & HCO3 Dissolved and undissolved organic mater Microorganisms Obtained by distillation, ion exchange, and reverse osmosis Ion exchange Makes use of filter o membranes in removing contaminants Advantages over distillation: o permit ease of operation, minimal maintenance, and more mobile facility Reverse Osmosis o Pressurized steam of water is passed parallel to the
1
inner side of membrane core
a
filter
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 meet extent shelf-life periods 7-14 days: expiration date after filling with a suitable solvent Example: Cloxacilin Sodium for Oral Solution, USP Anti-infective o Penicillin V Potassium for Oral Solution, USP o Anti-infective KCl for Oral Solution, USP K Supplement o Oral solutions Pediatric form of an adult product Reconstituting a dry powder mixture/extemporaneously compound an oral solution from bulk components Oral rehydration solutions Rapid fluid loss associated with diarrhea lead to: Dehydration Ultimately death in some patients particularly the infants Effective in treatment of patients with mild volume depletion 3 to 10% of body weight OTC, inexpensive and use diminished the incidence of complications associated parentally administered 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 achieve rehydration Examples: o Pedialyte solution Rehydrate solution o Oral colonic lavage solution Administration of oral laxative: laxative: Magnesium citrate or bisacodyl the night before Cleansing enema administered 2 to 4 hours prior to the procedure
Alternative method to prepare the gastrointestinal tract: Requires less time and dietary restriction and obviates cleansing enemas Entails oral administration of: balanced solution of electrolytes with PEG Adult dose: 4L, 240 ml per 10 minutes until 4L is achieved Magnesium citrate oral solution Citrate or citrate of magnesia Colorless to slightly yellow clear effervescent liquid, sweet acidulous taste and lemon flavor Excellent medium for the growth of molds and any molds spores: must be killed to remain stable 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 acid 67 mg in each millimeter of aqueous solution
Syrups Concentrated aqueous preparations of a sugar or sugar substitute with or without flavoring agents and medicinal substances Serves as: Pleasant tasting vehicle for medicinal substances in: Extemporaneous compounding of 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 commonly sucrose 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 sugar substances: 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 to make 100 ml of syrup Antimicrobial Agent The amount of preservative Varies with the proportion of water available for growth: 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 materials such 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 a flavored liquid
Percolation of either the source of medicating substance or 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 sucrose caramelizes Excessive heating convert syrups into its inversion form (Excessive heat Inversion Caramelization) Medicinal agents destroyed by elevated temperature Solution by Agitation Without Aid of Heat Dissolves with purified water Ingredients in a vessel larger than the volume of syrup to be prepared permitting thorough agitation of the mixture Addition of Sucrose to a Medicated Liquid Liquid or to Flavored Liquid Alcohol-soluble components Undesirable or unnecessary components of corresponding syrup Removed by mixing the tincture or fluid extract with water
Table 13.5: Examples of Oral Solutions by Category Oral Solution
Representative Commercial Products
Nortriptyline HCl
Pamelor (Novartis)
Oral
Fluoxetine HCl
Prozac Liquid (Dista)
Solution
Concentration of Commercial Product
Comments
10mg nortriptyline/5ml
Tricyclic antidepressant
20mg fluoxetine/5ml
For depression, obsessive compulsive disorder
Diphenoxylate HCl, atropine sulfate
Lomotil Liquid (Searle)
2.5mg diphenoxylate HCl, 0.025mg atropine sulfate/5ml
For diarrhea. Diphenoxylate is related structurally and pharcologically to the opioid meperidine. Atropine sulfate in subtherapeutic amounts discourages (by virtue of side effects) deliberate overdosage
Loperamide HCl
Imodium A-D Liquid (McNeil Consumer Products)
1mg loperamide HCl/5ml
For diarrhea in adults and children aged 6 years and older. Structurally related to haloperidol.
Haloperidol
Haloperidol Oral Solution
2mg haloperidol/ml
Perphenazine
Perphenazine Oral Solution
16mg perphenazine/5ml
Thiothixene HCl
Navane concentrate (Pfizer)
Primarily for severe neuropsychiatric conditions when oral medication is preferred and tablets and capsules are impractical. Concenreted solutions used by adding desired amount of concentrate bt calibrated dropper to soup or a beverage.
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Theophylline Oral Solution (Roxane)
Theophylline
Magnesium USP
Citrate,
Sodium phosphate
Phospho-Soda (Fleet)
Prenisolone phosphate
Pediapred (Medeva)
sodium
Sodium fluoride
Potassium chloride
Docusate sodium
Ferrous sulfate
Oral
Magnesium citrate equivalent to 1.55-1.9 g/100ml magnesium oxide
Discussed in text.
2.4g monobasic sodium phosphate, 0.9g dibasic sodium phosphate/5ml
Solution
Pediaflor Drops (Boss)
KaoChlor 10% Liquid (Adria)
Colace syrup (Shire)
Fer-In-Sol Drops Johnson Nutritional)
80mg theophylline/15ml
Alcohol-free solution for treatment of bronchial asthma and reversible bronchospasm associated with chronic bronchitis and emphysema.
(Mead
5mg prednisolone phosphate)/5ml
(as
sodium
Synthetic adrenocortical steroid with mainly glucocorticoid properties indicated for endocrine, rheumatic, collagen, allergic, and other disorders.
0.5 mg/ml
Prophylaxis of dental caries; for use when community water supply is inadequately fluoridated.
20 mEq KCl/15ml aqueous vehicle
For hypopotassemia (low blood level of potassium). Condition may be prompted by severe or chronic diarrhea, low dietary intake of potassium, increased renal excretion of potassium, other causes. Solution is diluted with water or fruit juice.
in
flavored
10mg docusate sodium/ml
Usually 50-200mg measured by calibrated dropper, mixed with milk, fruit juice, other liquid to mask taste. Softens fecal mass by lowering surface tension, permitting normal bowel habits, particularly in geriatric, pediatric cardiac, obstetric, and surgical patients. Taken for several days or until bowel movements are normal.
15mg/0.6ml
For prevention and treatment of iron deficiency anemias. Usual propylactic dose 0.3 or 0.6ml, measured by calibrated dropper, mixed with water or juice. Dosage for intended primarily for infants and children.
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Cimetidine HCl
Tagamet HCl Liquid (SmithKline Beecham)
300mg/ml
For peptic ulcer disease, hypersecretory conditions, ZollingerEllison syndrome.
Methadone HCl
Methadone HCl (Roxane)
1 or 2 mg/ml
For relief of severe pain; detoxification, maintenance treatment of opioid addiction.
8,000 U/ml
Water-insoluble ergocalciferol (vitamin D2) in propylene glycol. Usual propylactic dose about 400U; therapeutic dose may be as high as 200,000-500,000 U daily in treating rickets.
Ergocalciferol
Calciferol Drops (Schwarz)
pathologic e.g.,
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