midterm 2 Flashcards
Drug solubility In pharmaceutical solutions both the ___ and the ___ are legally required to be present in solution over the shelf-life of the formulated product.
THERAPEUTIC AGENTS
EXCIPIENTS
The dissolution of a therapeutic agent in water involves several key molecular steps:
REMOVAL OF A MOLECULE OF THE DRUG FROM THE SOLID STATE
FORMATION OF A CAVITY WITHIN THE SOLVENT
ACCOMMODATION OF THE DRUG MOLECULE
breakage of solute-solute and solvent-solvent bonds
ENDOTHERMIC PROCESSES
It occurs whenever the Gibb’s free energy of the process is NEGATIVE and involves a balance between the enthalpy of dissolution and the associated entropy at the temperature of dissolution (T).
DISSOLUTION
It is a thermodynamic potential that measures the maximum amount of reversible work that can be performed by a thermodynamic system at constant temperature and pressure.
GIBB’S FREE ENERGY
Refers to the thermodynamic capacity of API.
ENTHALPY
Refers to the m easurement of the degree of randomness or spontaneity of API.
ENTROPY
Factors affecting the solubility of therapeutic agents:
• molecular weight
• Volume
• radius of gyration Density
• number of rotatable bonds
• hydrogen bond donors and
• hydrogen bond acceptors
as the melting point of the therapeutic agent is increased, the solubility would be expected to decrease
INVERSELY RELATED TO THEIR MELTING POINTS
It is directly affected by both the type of chemical substituent groups and the substituent position.
THERAPEUTIC AGENT
thesolubilitiesoftherapeuticagentsthatareeitheracidsorbases (representing the vast majority of drug substances) are __
pH-DEPENDENT
are physiologically inert compounds.
EXCIPIENTS
It facilitates the administration of the dosage form, e.g. pourability, palatability
EXCIPIENTS
• protect the formulation from issues regarding physical and chemical stability
• enhance the solubility of the therapeutic agent.
EXCIPIENTS
It is commonly used due to the low cost and low toxicity of this ingredient.
PURIFIED WATER, USP
■ It is prepared by distillation, ion exchange methods or by reverse osmosis.
■ The solid residue (obtained after evaporation) is less than 1 mg per 100 ml of evaporated sample.
PURIFIED WATER, USP
■ It must not be used for the preparation of parenteral formulations.
PURIFIED WATER, USP
It is an odorless, sweet liquid that is miscible with water and whose co-solvency properties are due to the presence of three hydroxyl groups (termed a triol).
GLYCEROL (GLYCERIN)
It has similar co-solvency properties to ethanol.
GLYCEROL
It contains between 94.9 and 96.0% v/v ethyl alcohol (ethanol) and is commonly used as a co-solvent, both as a single co-solvent and with other co-solvents, e.g. glycerol
ALCOHOL USP
It is an odourless, colourless, viscous liquid diol that contains two hydroxyl groups. It is used in pharmaceutical preparations as a co-solvent, generally as a replacement for glycerin.
PROPYLENE GLYCOL USP
It is a polymer composed of repeating units of the monomer ethylene oxide, Lower-molecular-weight grades (PEG 200, PEG 400) are preferred as co-solvents in pharmaceutical solutions
POLY(ETHYLENE GLYCOL) PEG
These are chemicals that possess both hydrophilic (water-liking) and hydrophobic (water-disliking) regions.
SURFACE-ACTIVE AGENTS
It would prevent drug absorption across biological membranes
DRUG-POLYMER COMPLEX
These are employed within pharmaceutical solutions to control the pH of the formulated product and, in so doing, optimise the physicochemical performance of the product.
BUFFERS
Examples of buffer salts used in pharmaceutical solutions
- ACETATES (ACETIC ACID AND SODIUM ACETATE)
- CITRATES (CITRIC ACID AND SODIUM CITRATE)
- PHOSPHATES (SODIUM PHOSPHATE AND DISODIUM PHOSPHATE)
are employed in liquid formulations designed for oral administration specifically to increase the palatability of the therapeutic agent.
SWEETENING AGENTS
The main sweetening agents employed in oral preparations are:
SUCROSE
LIQUID GLUCOSE
GLYCEROL
SORBITOL
SACCHARIN SODIUM
ASPARTAME
It is used either as the sole sweetening agent or in combination with sugars or sorbitol to reduce the sugar concentration in the formulation.
SACCHARIN SODIUM
The administration of oral solutions to patients is usually performed using a
SYRINGE
SMALL-METERED CUP
TRADITIONAL 5-ML SPOON
The viscosity of pharmaceutical solutions may be easily increased (and controlled) by the:
ADDITION OF NON-IONIC OR IONIC HYDROPHILIC POLYMERS
cellulose derivatives
NON-IONIC (NEUTRAL) POLYMERS
examples of non ionic (neutral) polymers
METHYLCELLULOSE
HYDROXYETHYLCELLULOSE
HYDROXYPROPYLCELLULOSE
polyvinylpyrrolidone
HYDROXYPROPYLCELLULOSE
sodium carboxymethylcellulose (anionic) – sodium alginate (anionic)
IONIC POLYMERS
These are molecules that are redox systems that exhibit higher oxidative potential than the therapeutic agent or, alternatively, are compounds that inhibit free radical-induced drug decomposition.
ANTIOXIDANTS
Examples of antioxidants that may be used in oil-based solutions include:
BUTYLATED HYDROXYTOLUENE (BHT)
BUTYLATED HYDROXYANISOLE (BHA)
PROPYL GALLATE
These are included in pharmaceutical solutions to control the microbial bioburden of the formulation.
PRESERVATIVES
These are employed whenever the unpalatable taste of a therapeutic agent is apparent, even in the presence of the sweetening agents.
FLAVORS
These are generally natural or synthetic water soluble, photo-stable ingredients that are selected according to the flavour of the preparation.
COLOURS
These are viscous preparations that contain the therapeutic agent dissolved in a vehicle composed of a high percentage of sucrose and, if required, other sweetening agents.
LINCTUSES
It occurs whenever the Gibb’s free energy of the process is negative and involves a balance between the enthalpy of dissolution and the associated entropy at the temperature of dissolution (T).
DISSOLUTION
Oral Liquid Dosage Forms
SYRUP
ORAL SOLUTION
ORAL DROP
ORAL EMULSION
MIXTURE
LINCTUSES
ELIXIR
The aqueous solubility of the therapeutic agent is _____ of the formulation. Under these circumstances the therapeutic agent may be ______ and formulated as an oral solution.
- high at the selected pH
- readily incorporated into the vehicle
The aqueous solubility of the therapeutic agent is _____ of the formulation, i.e. the aqueous solubility is less than the requested concentration of therapeutic agent.
- moderate at the selected pH
Example of alternative-dosage form
SUSPENSION
commonly employed co-solvents
GLYCEROL
PROPYLENE GLYCOL
ETHANOL
POLY(ETHYLENE GLYCOL)
most commonly used vehicle for oral administration
PURIFIED WATER USP
Control of the pH in the formulation is achieved using a buffer that does not adversely affect the solubility of the therapeutic agent.
solubility of acidic compounds increases as the pH of the solution is increased (above the pKa) and the solubility of basic compounds increases as the pH is lowered below the pKa.
these are preferred due to the lack of toxicity of water as the vehicle
AQUEOUS SOLUTIONS
The solid residue (obtained after evaporation) of purified water usp is
less then 1mg per 100 ml of evaporated sample
main co-solvents used in the formulation of oral solutions
GLYCEROL (GLYCERIN)
ALCOHOL USP (CH3CH2OH)
PROPYLENE GLYCOL USP
POLY(ETHYLENE GLYCOL) PEG
SURFACE-ACTIVE AGENTS
DRUG-POLYMER COMPLEX
increasing the viscosity of some formulations may increase the palatability.
VISCOSITY-ENHANCING AGENTS
It may be easily increased (and controlled) by the addition of non-ionic or ionic hydrophilic polymers.
VISCOSITY OF PHARMACEUTICAL SOLUTIONS
it possess a broad spectrum of antimicrobial activity encompassing Gram-positive and Gram-negative bacteria and fungi
PRESERVATIVES
be chemically and physically stable over the shelf-life of the product
have low toxicity.
PRESERVATIVES
preservatives available for use in pharmaceutical solutions for oral use
BENZOIC ACID AND SALTS (0.1 to 0.3%)
SORBIC ACID AND SALTS (0.05 to 0.2%)
ALKYL ESTERS AND PARAHYDROXYBENZOIC ACID (0.001 to 0.2%)
liquid products to be used as injections, eye drops or vaccines sterility, these tests are necessary as additional tests.
APYROGENICITY TESTING
PARTICULATE MATTER TESTING
It refers to the property of a substance or a product that is free from pyrogens
Apyrogenicity
are substance that can induce Fever when introduced into the body.
They are often bacterial endotoxins, which are components of the cell wall of Gram-negative bacteria
Pyrogens
