Solutions in Therapy Flashcards
Solutions
are liquid preparations containing one
or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents
Solutions are often classified
due their composition or use
Solution examples
Syrups (aqueous with sugar), hydroalcoholic (water + ethanol), elixirs, tinctures,
etc.
– Oral, otic, ophthalmic, topical, etc
• Since a medicinal agent is administered in solution, it is usually assumed:
That the agent, as well as other solutes, are soluble or at least partially aqueous
soluble
Since it is already in solution, it is expected that
absorption occurs faster than from a solid or suspension dosage form of the same medicinal agent
– Pharmacist is aware of the
solubility and stability of each solute in the solution
to avoid chemical and physical interactions that will affect the product
• Solubility
The amount of solute that can dissolve in a given quantity of solvent at
a particular temperature
A saturated solution is
one that contains the maximum quantity of dissolved solute
at a given temperature
Solute-solute and solvent-solvent forces must
be overcome by solute-solvent attractive forces for dissolution to happen
Solubility may be increased by selecting a
different solubilizing agent, different
chemical salt form, alteration of the pH of the solution or substitution in part or in
whole of the solvent
An increase in temperature usually results
in an increase in solubility
Prediction of solubility is based upon
molecular structure and functional groups
– Like dissolves like
Salts of monovalent cations (Na, K, Li, NH4) are generally
water soluble
Salts of divalent cations (Ca, Mg, Hg) are
often less soluble
Halogen groups and increases in molecular weight tend to
decrease water solubility
Organic compounds may be somewhat more aqueous soluble if they
contain
polar groups that are capable of hydrogen bonding
Greater the number of polar groups
, the better likely the aqueous solubility
Polar groups include: -OH, -CHO, -COOH, -C=O, -NO2, -NO3
, -NH2
, -SO3H
Choice of solvents is based upon factors such as
solubility, clarity, toxicity,
compatibility with other formulation components, odor, color, cost and
route of administration
Co-solvents are often employed
– To enhance solvation ability of water
– To contribute to a product’s chemical and/or physical stability
Examples of co-solvents
o Ethyl alcohol, glycerin and propylene glycol often used
Alcohol
Also called ethyl alcohol, ethanol
-94.9-96% C2H5OH v/v
-
Alcohol is
Miscible with water and is able to dissolve many water insoluble ingredients
such as drug substances, flavorants, colorants and antimicrobial preservatives
Ethanol may act as a
antimicrobial alone or with other preservatives
FDA limits alcohol content in OTC oral products
Concern about undesirable pharmacologic and toxic effects
– Limits:
❖For children < 6 years of age – 0.5%
❖For children 6-12 years of age – 5%
❖For children > 12 years of age and adults – 10%
Glycerin, USP
Also called glycerol
- is a natural compound derived from vegetable oils or animal fat
- Miscible with water and alcohol
Glycerin characteristics
- Clear syrupy liquid with a sweet taste
- Has preservative properties at higher concentrations
- Used as a stabilizer and an auxiliary solvent in conjunction with water or alcohol
• Used in many internal preparations
Propylene Glycol, USP
Clear, viscous liquid
• A synthetic product obtained from the hydration of propylene oxide
• Miscible with water and alcohol
• Frequently substituted for glycerin in modern pharmaceutical formulations
Purified Water, USP
s obtained from EPA compliant water treated mainly by distillation, ion exchange or reverse osmosis
- Not intended for use for parenteral administrations (i.e., injections)
Note abt Purified water
Ordinary drinking water from the tap is not acceptable for the manufacture
of most aqueous preparations because of possible incompatibilities
between dissolved solids and the medicinal agents
Water permitted for parenteral administration:
Water for Injection, USP;
Bacterostatic Water for Injection, USP; Sterile Water for Injection, USP
Strengths of preparations are usually expressed
in terms of percent strength
To hasten the dissolution of a slow dissolving material, one may try to:
- Apply heat
- Reduce particle size of solute
- Use a solubilizing agent
- Vigorously agitate mixture (effective stirring)
- Lower viscosities of solvents if not only aqueous
Note:
Increased temperatures cannot be maintained for pharmaceuticals. Also, elevated temperatures may result in loss of volatile co-solvents (e.g., alcohol) and increase in the rate of degradation of drug or excipients.
Ratio strength weight in volme
-:- w/v Grams of constituent in stated milliliters of preparation
Dry mixtures for solution
Some drugs have insufficient stability in aqueous solution for an extended
shelf-life, e.g., antibiotics
• These products are provided as dry powder or granule form for reconstitution immediately prior to dispensing
- This dry powder contains all of the formulative components except for the
solvent
Dry powder: Once reconstituted, the solution remains
stable for a certain labeled period
(7 to 14 days) when stored in the refrigerator; this period is sufficient for
the completion of the regimen prescribed
Solutions intended for oral administration may contain
– Flavors and colors to make them more palatable and attractive
– Stabilizers to maintain chemical and physical stability
– Preservatives to prevent growth of microorganisms
Pharmacist may be called on to
– Dispense a commercially prepared solution
– Dilute the concentration of a prepared solution (e.g., to make a pediatric
solution from an adult product)
– Prepare a reconstituted solution
– Extemporaneously compound an oral solution from bulk ingredients
Oral rehydration solutions
Rapid fluid loss associated with diarrhea can lead to dehydration and death
- common in young children and elderly
-
Why would you need oral rehydration solutions
Small intestine secretes far more fluid and electrolytes than normal exceeding the amount
the large intestine can reabsorb; the fluid loss, mainly extracellular fluid, leads to progressive
loss of blood volume and hypovolemic shock
Goal of Oral rehydration solutions
o Usually effective in treatment of mild volume depletion: 5-10% body weight
o Available OTC – Typically as a powder that is added to a specific amount of water
Oral rehydration solutions example
Pedialyte (Abbott)
Oral colonic lavage solution
To prepare for procedures such as a colonoscopy, the bowel must be cleared;
material remaining in the bowel results in problems during the procedure
-Bowel clearance entails oral administration of a balanced solution of
electrolytes with PEG-3350
-Product needs to be refrigerated after reconstitution
PEG
acts as the osmotic agent in the GI and the balanced electrolyte concentration results in virtually no net absorption or secretion of ions
o A large volume (4 L) of this solution is administered
Magnesium citrate oral solution
Also known as, citrate or citrate of magnesia
– An essentially colorless, effervescent liquid having a sweet, acidulous taste and
a lemon flavor
– During preparation, liquid is boiled; final solution may be sterilized
– Employed as a saline laxative that is best taken refrigerated
Sodium citrate and citric acid oral solution
Citric acid and sodium citrate solution
– Used as a systemic alkalinization for patients with need of maintaining alkaline urine for the treatment of cystine calculi (a type of kidney stone)
– Also used as an adjuvant in treatment of gout
Syrups
Concentrated, viscous aqueous preparations of sugar or sugar substitute with or without flavoring agents and medicinal substances
- helps w taste
Most commonly sugar employed in syrups
sucrose
- Sorbitol, glycerin, propylene glycol, methylcellulose, hydroxyethylcellulose – Often substituted for sucrose
Non-medicated or flavored vehicles
Syrups containing flavoring agents, but no
drug
- Can be used in reformulating a medication only available in a solid form
– Drug stability, solubility and bioavailability must be considered, case-by-case
– Can be prepared as either solution or suspension
Note abt syrup
Water-soluble, aqueous-stable drug may be added to a flavored syrup provided
other components of the formulation are also compatible
Most syrups contain
High sugar concentrations –
- Strongly resistant to microbial growth, as it ties up water
- Antimicrobial preservatives
- Water-soluble flavors and colors
– Water
– Drug – Water-soluble, aqueous-stable
– Other solvents (e.g., alcohol), solubilizing agents, thickeners and/or stabilizers, if
needed
Formulation note
Use of minimal amount of free water to dissolve solids minimizes chance of microbial growth
Elixirs
Clear, sweetened hydroalcoholic oral solutions
• Contain less sugar than syrups – Therefore, less sweet and less viscous
• Flavorings and colorings to increase patient acceptance
Alcohol content dependent upon the aqueous solubility of the components
Poorer the
water solubility, the higher the proportion of alcohol
Elixir co-solvents
Glycerin and propylene glycol
Elixirs with 10-12% alcohol are
usually self-preserving
Elixir storage
should be stored in tight, light resistant containers and protected from excessive heat
- most often observed in extemporaneous compounding
Tinctures
Alcoholic or hydroalcoholic solutions prepared from vegetable materials or chemical substances
• Oral and topical administration, depending on the tincture
Tinctures contain
15-80% alcohol
– Keeps extractives in solution
– Protects against microbial growth – Self-preserved
– Sometimes co-solvents needed to enhance stability and/or solubility of solutes
Tinctures storage
Need to be kept in tightly stoppered, light resistant containers protected from excessive temperatures due to alcohol content
Spirits
Alcoholic/hydroalcoholic solutions of volatile substances (usually oils)
- Alcohol concentration – Generally > 60%
- Normally when mixed with water, volatile substances separate out and solution forms a milky preparation
Spirits uses?
As flavoring agents, e.g., Peppermint Spirit
– For medicinal purposes, e.g., Camphor Spirit for topical administration
Generally, the topical solutions employ an_____, whereas the
topical tinctures characteristically employ an______
- Aqeuous vehicle
2. Alcoholic vehicle
Sprays
Aqueous or oleaginous solutions administered topically
– Coarse droplets or fine solids applied via spray bottles or atomizers
Sprays characteristics
Usually to nasopharyngeal tract (e.g., congestions and inflammation) or skin
o Insulin and glucagon may be administered nasally
o Anti-infective and antifungal are examples of skin sprays
Coal tar topical solution
An alcoholic solution containing 20% coal tar and 5% polysorbate 80
– Final content is 81-86% alcohol
– Diluted formulation used as a local antieczematic for topical skin conditions
Chlorhexidine gluconate solution
A broad spectrum antiseptic used as a surgical scrub, hand wash, skin wound and antiplaque, antigingivitis
mouth wash
Povidone iodine topical solution
Chemical complex of iodine and polyvinylpyrrolidine (PVP)
-Approximately 10% iodine available to be released when applied to skin
– Used as a surgical scrub and non-irritating antiseptic
Thimerosal topical solution
Water soluble organic mercury antibacterial
o Buffered to maintain alkalinity (pH ~10) for stability
o Solution protected from light
Thimerosal topical solution uses
Was used mainly to disinfect skin prior to surgery and as a first aid to abrasions
and wounds
– Was used as a preservative in vaccines and other biologic products
– Withdrawn from the market
Vaginal solutions (Douches)
Concentrated powders – Usually diluted or prepared as solutions by patient
– For irrigation, hygienic cleansing of the vagina
– Some douches contain therapeutic anti-infective agents
Rectal solutions
– Retention enemas
- Evacuation enemas
Retention enemas –
For local effects or systemic absorption
o Minimizes undesirable GI effects seen in oral administration
o Blood levels usually obtained within 30 minutes following instillation
Evacuation enemas
To cleanse the bowel
Non-aqueous solutions
Liniments
Collodions
Liniments
Alcoholic or oleaginous liquid preparation intended to be rubbed with friction and
massaged onto the skin
may be solutions, emulsions or suspensions depending upon the materials and
preparation procedure
➢FOR EXTERNAL USE ONLY
Alcoholic liniments –
Used when rubefacient, counterirritant or penetration action is desired
Oleagineous liniments
Primarily employed when massage is desired; less irritating to skin than
alcoholic liniments
Collodions
Mainly solutions of pyroxylin in vehicle of alcohol and ether with or without drug
– Painted/applied to skin and allowed to dry to form a somewhat flexible film used to
occlusively protect the skin or retain a dissolved drug in contact with skin for a
prolonged period of time
➢FOR EXTERNAL USE ONLY
Principal methods of drug extraction
Maceration
Percolation
Maceration
o Process in which the properly comminuted drug is permitted to soak in solvent until the
soluble material is dissolved
o Material is placed in a stoppered vessel and the material is soaked and repeatedly
agitated for a period of time, usually 2-14 days
o Alternative method is to place material in a porous cloth bag that is suspended in
solvent until all soluble material is dissolved
o Maceration is usually conducted at 15-20 °C
Percolation
Process in which a comminuted drug is extracted by the slow passage of solvent
through a column of the drug
Advantages of solutions
- The drug is already dissolved in solvent
system; drug action can be rapid - Dose uniformity and specific volumes can
be measured accurately allowing for flexible
dosing - Oral solutions are usually easily swallowed
as opposed to solid dosage forms - Generally, easy to manufacture
DisAdvantages of solutions
- Drug instability is increased when drug is in
solution - Bulky and less convenient for patients to
transport compared to solid dosage forms - Many drugs are insoluble or poorly soluble
in water - Measuring device needed for administration
