Solutions

Combines Part 1 & Part 2 from the lecture

solution

liquid dosage form

solution (USP def.)

a preparation that contains one or more dissolved chemical substances in a suitable solvent or mixture of mutually miscible solvents

True

T/F: The defining characteristic of a solution is all solutes are uniformly dispersed as individual molecules

drug molecules, excipient molecules

What in a solution are present as individual molecules

False

T/F: There are particles in a solution

homogenous

A solution is what?

Homogeneous

Any sample of any size taken from any part of the container has the same concentration of all solutes as any other sample of any size taken from any other part of the container

True

T/F: Solutes do not separate from the solvent nor each other during storage.

less

The concentration of each solute in a solution is ____ than its solubility in the mixture

True

T/F: There are solution dosage forms designed for almost every route of administration

interchangeable

A solution is NOT …

highest dissolved concentration

The solubility of a drug is the _____ that can be prepared in a particular mixture

Polarity of the solvent system

The major factor on solubility is what?

Higher

Most things are soluble at what temperature?

Fridge temp & room temp

With storage temperature, need to consider the range of what 2 values?

Cosolvent

mixture of miscible liquids used as solid (ex.water & alcohol)

Complex agents

interaction w/ 2 differs compounds resulting in higher solubility

Soluble agents

self-form surfactants

Cosolvent, Complexing Agents, Solubilizing Agents

Some excipients may increase the apparent solubility of another solute in the mixture through …

Weak electrolytes solubility

What does solution pH determine?

2 – 8

The range of acceptable pH values for oral solutions is …

1 – 8

The range of pH values in the body is …

weak acids

Solubility of _____ increases as pH of the mixture is increased

weak bases

Solubility of _____ decreases as pH of the mixture is increased

Precipitation

A change in product pH due to adding anything to the solution may change the solubility of one or more solutes

This can cause what?

Highly polar

Water is …

Moderately polar

alcohol

polarity intermediate

Water & alcohol mixture have what?

Increase solubility of the drug/other solutes

What can excipients do to solutions?

True

T/F: There is a weighted average between water & alcohol when mixed.

Cyclodextrins

What is a common complexing agent

higher

The complex of itraconazole and ß-cyclodextrin has much ____ solubility in water than itraconazole alone

micelles form

Hydrophobic solutes partition into the micelle core, meaning that …

Excipients increasing drug solubility/other solutes

The following image is an example of what?

homogenous (no prep required), customizable doses, easily swallowed

What are the advantages for solutions?

packaging & ship are expensive

One of the disadvantages for solutions is that water is heavy, meaning that

chemical degradation reactions occur frequently in solutions

Why is the shelf life shorter in a solution than solid dosage form?

low

The solubility of some drugs is too ___ to make a solution with a reasonable volume

calibrated device, patient/caregiver training

For accurate dose measurement, what is required?

Solvent

always contain water, with the purpose to dissolve all solutes

single solvent/ cosolvent system

Solution can contain …

cosolvent system

2+ mixture of miscible liquids used as solvent

Purified water USP

What is used in oral or topical solutions

Municipal drinking water or tap water

What is NOT used in oral/topical solutions

Contains ions that cause precipitation/catalyze drug degradation

Why is municipal tap water not accepted for pharmaceutical solutions?

Divalent Cations

What catalyze drug degradation reactions

False

T/F: Purified Water USP contains more than 0.01 mg/mL dissolved solutes

distillation, reverse osmosis, or ion exchange, or a combo of these method

Purified Water USP may be prepared by what?

Ion exchangers

remove ionic solutes (Ca2+, Mg2+, SO42–, Fe2+, Cu2+, SO42–)

Reverse osmosis

removes ions and organic solutes

Ca2+, Mg2+, SO42–, Fe2+, Cu2+, SO42–

The following ion can:

precipitate drugs/other solutions in a drug product

catalyze drug degradation reactions

contain dissolve organic compounds (drugs)

Alcohol (ethanol)

Miscible with water

May be used in oral or topical products

Intoxication caution

True

T/F: Products must be labeled w/alcohol content while non-drug products are exempt from this requirement

< 10% v/v

FDA limit alcohol content: For adults & children >12 it is …

<5% v/v

FDA limit alcohol content: For children 6-12 it is …

<0.5% v/v

FDA limit alcohol content: For children <6 it is …

Glycerin

Miscible with water

Oral or topical products

Similar polarity to alcohol

Used as alcohol substitute

Propylene glycol

Miscible with water

Oral or topical products

Similar polarity to glycerin and alcohol

Used as an alcohol or glycerin substitute

Polyethylene glycol 300/400

Miscible with water

Oral or topical products

Similar polarity to alcohol, glycerin, propylene glycol

Polyether with hydroxyl group at each end

Number indicates approximate molecular weight

molecular weight

What is the difference between the Polyglcol 300 vs 400

Isopropyl alcohol

Miscible with water

Topical products only

Similar polarity to ethanol

Acetone

Miscible with water

Topical products

Oils

Lower polarity than alcohol

Not miscible with water

Maybe miscible w/ some alcohols

Used in topical solutions

more polarity

When using oil, why is medium chain triglyceride better to use than vegetable oil?

Isopropyl myristate, Isopropyl palmitate

Similar to MCT (solvent prop); used in topical products, cosmetics,

pH adjusters

meets the target pH range through adding HCl or NaOH

HCl

added to reduce the pH to the target range if the pH is too high after mixing all other components

NaOH

added to increase pH to the target range if the pH is too low after mixing all other components

NaOH

In this example what should be added to meet the pH target range for this solution

Drug/excipient solubility, CHEM stability, & patient safety

The target pH range includes:

True

T/F: The product is dependent on the chemical stability

buffer

Minimize pH changes due to small additions of H+ or OH

buffer

a weak electrolyte in solution with pH within 1 unit of it’s pKa value

H+ or OH–

_______ may come from containers or reactions within the product

3.5-5.5

Sodium acetate pKa 4.5, what is the buffer pH range?

6.2-8.2

Sodium phosphate (NaH2PO4– /Na2HPO42–) pKa 7.2, the buffer range from pH is

2.1 - 7.4

Sodium citrate has 3 carboxyl groups – pKa 3.1, 4.8, 6.4; the buffer range is

easier dose measurement & administration(less spilling) + placebo effect to induce patient confidence

Why would higher viscosity than water be desired?

polymer

compound w/ repeating unit structure

Polyvinylpyrrolidone

water soluble polymer that is synthetic that increases viscosity a lot

Methylcellulose 2%

make solution more resistant

HPC, HPMC

soluble water polymer that do the same thing as methylcellulose

Xanthan gum

help w/ developing bacteria & collecting it (derived from nature)

Flavors

mask objectionable tastes and improve patient adherence

Colors

enhance patient perception and recognition of flavor

Sweeteners

add sweet sensation to flavor to mask objectionable tastes

Sucrose

promotes tooth decay & increases blood glucose

False

T/F: Zero calories’ sweeteners like Sucralose, Saccharin & Aspartame are less sweet than Sucrose.

Sorbitol

The only Zero calorie sweetener that is less sweet than sucrose is …

Preservatives

inhibit microbiological growth from microorganisms that are introduced during or after manufacturing

Preservatives used in oral products

Benzoic acid, Sorbic acid, benzyl alcohol are example of what?

Methylparaben

prevent mold growth

Antioxidants

prevent drug degradation through protect the drug and other excipients from oxidation

True

T/F: One way to remove oxygen is to have compounds consume free oxygen (O2) in solution quickly to reduce the oxidation of other solutes

Chelating agents

bind to metal ions in solution to inhibit ion-catalyzed oxidation of other solutes

Ascorbic acid

Vitamin C, great antioxicant for the body

compounds that consume O2 quickly

Ascorbic acid, sodium bisulfite, sodium metabisulfite, & propyl gallate are examples of …

chelating agents

Ethylene diamine tetraacetic acid (EDTA)

Edetate disodium

Sodium citrate

are examples of …

flavoring

In this example, Citric acid monohydrate is being used for

growth prevention

In this example, methylparaben sodium is being used for …