T1 - Week 5 Flashcards
What is the difference between acids and bases?
Acids donate protons, bases gain protons
What is a buffer?
An aqueous solution that has the ability to resist a change in pH
What are the components of a buffer?
- Weak acid and conjugate base (salt of acid)
- Weak base and conjugate acid (salt of base)
What is a buffer capacity?
The ability of a buffer solution to resist changes in pH upon addition of acid and bases
How are buffers used in pharmaceutical products?
- To control the pH of the formulated products
- To optimize the physicochemical performance of the product enhancing solubility and stability of products
What are examples of pharmaceutical buffers?
- Acetates
- Citrates
- Phosphates
- Borates
What are factors for selecting a buffer system?
- Nontoxic
- Nonirritating
- No disagreeable odor or taste
- pH range of 4-8
- Buffer capacity is less than 0.05 is optimal
Describe the steps of preparing a buffer solution?
- Determine the optimal pH for the product
- Select a weak acid with a pKa near the desired pH
- Calculate the salt to acid ratio using Henderson-Hasselbach
- Specify the desire buffer capacity of the product
- Calculate buffer concentration for buffer capacity using Van Slyke
- Determine the pH and buffer capacity of solution by using a pH meter or paper
What buffers would you use for acidic solutions?
- HCl (1-3)
- Citrate buffer (2.5-6.5)
- Acetate buffer (3.6-5.6)
What buffers would you use for neutral solutions?
Sorenson’s phosphate buffer (6-8)
What buffers would you use for basic solutions?
- Sodium bicarbonate (8-9)
- Sodium bicarbonate/sodium carbonate (9-11)
- NaOH (11-13)
What are the desirable properties of salts in drugs?
- Increase solubility
- Increase stability
- Reduce toxicity
- Improve absorption
- Improve manufacturing process
How do you select counterions based on pKa for acidic and basic drugs?
- Acidic: pKa of counterion must be 2 pH units higher than pKa of drug
- Basic: pKa of counterion must be 2 pH units lower than pKa of drug
What is the relationship between solubility and dissolution rate?
Salt formation may improve solubility and dissolution rate
What are examples of counterions for weak base drugs?
- Hydrochloride
- Mesylate
- Hydrobromide
- Acetate
- Fumarate
What are examples of counterions for weak acid drugs?
- Sodium
- Calcium
- Potassium
What are the characteristics influencing selection of counterions?
- pKa rule
- Solubility and dissolution rate
- Lipophilicity
- Hygroscopicity
- Chemical stability
- Flowability
- Corrosiveness of counterions
- Compatibility with excipients
- Route of administration
- Controlled release dosage forms
How can lipophilicity decrease water solubility?
- Increase chemical stability with certain APIs
- Hydrophobic salts may increase membrane permeability of hydrophilic molecules
What is hygroscopicity?
The ability of a material to absorb and retain moisture at various temperature and humidity conditions
Would drugs have a low or high hygroscopicity?
Low to easily degrade in the presence of water
What counterions are used to avoid hygroscopicity?
Very polar and hydroscopic salts of mineral acids
What degrades hydrolyzable drugs?
pH alterations in the salt
In regards to chemical stability pH changes can cause APIs to do what?
- Reactivity of API with excipients
- Instability, degradation, or impurities
What is flowability?
The ability of the powder blend to easily flow with consistency into the manufacturing equipment is essential
How can poor flowability affect final products?
- Unacceptable uniformity content
- Weight variation
- Physical inconsistency
What structures are preferred for flowability?
Crystalline
What is used to mask the corrosiveness of drugs?
Salts such as HCl and methanesulfonate
Should counterions interact with excipients?
No
What is the main issue of using injectable drugs?
Poor solubility of drugs in a limited number of solvents
What are common anions for injectables?
- Maleate
- Chloride
- Sulfate
- Acetate
What are common cations for injectables?
- Sodium
- Potassium
- Calcium
What are common anions for oral drugs?
- Chloride
- Sulfate
- Maleate
What are common cations for oral drugs?
- Sodium
- Potassium
- Calcium
What are the properties of salts in regards to controlled release dosage forms?
May alter dissolution rate and release from formulation
How do you decrease GI tract irritation and side effect from a drug?
Salts
Define excipient
Any substance other than the active drug or pro-drug that is included in the manufacturing process or is contained in finished pharmaceutical dosage forms
What is the general purpose of excipients
- Protect, support, or enhance stability of formulation
- Add bulk to formulation
- Improve patient acceptance
- Help improve bioavailability of API
- Enhance overall safety and effectiveness
Excipients are classified based on what?
- Origin (animal, vegetable, mineral, synthetic sources)
- Pharmaceutical formulation type (liquids, solids, and semi-solids
- Function (sweetener, humectant, wetting agent)
What makes an excipient ideal?
- Chemically stable
- Non-reactive
- Low equipment and process sensitive
- Inert to human body
- Non-toxic
- Acceptable taste and smell
- Economical
- Efficient with regards to intended use
What are examples of drug-excipient interactions?
- Physical
- Chemical
- Biopharmaceutical
What are the physical interactions of drug-excipient interactions?
- Rate of dissolution
- Dosage uniformity
- Difficult to detect
- No chemical changes
- May be beneficial
What are examples of physical interactions?
- Complexation
- Adsorption
- Solid dispersion
What are the chemical interactions of drug-excipient interactions?
- Formation of unstable compounds
- Generally try to avoid these interactions
What are examples of chemical interactions?
- Hydrolysis
- Oxidation
- Racemization
- Polymerization
- Maillard reactions
- Photolysis
What are the biopharmaceutical interactions of drug-excipient interactions?
- Effects observed after administration
- Cause alteration of rate of absorption
What are examples of bio pharmaceutical interactions?
- Premature breakdown of enteric coating
- Interactions with adjunct therapy
- Increase GI motility
How important are excipient-excipient interactions?
- Rare but important
- May be desirable or undesirable
What is the importance of package-excipient interactions?
Excipients must undergo same testing as API’s in terms of reactions with packaging, stability, and safety
What are the general types of excipients?
- Fillers/Diluents
- Binders
- Disintegrants
- Lubricants
- Glidants
- Wetting agents and surfactants
- Colorants
- Sweetners
- Flavorings
- Coatings materials
What are fillers/diluents for?
65-85% of oral formulations that bulks the drug
What are examples of fillers/diluents?
- Lactose
- Mannitol
- Cellulose
What is the purpose of binders?
Holds API and inactives together, 2-5%
What are examples of binders?
- HPC
- HPMC
What is the purpose for disintegrants?
Reduce cohesive forces and speed time for tablet to break apart, 2-5%
Has an affinity for water to draw water into tablet
What are examples of disintegrants?
- Starches
- Clay
- Cellulose
What are lubricants for?
- Hydrophobic
- Used to aid manufacturing process that can slow dissolution
What are glidants for?
- Used in manufacturing to improve flow of powder blends
- Some lubricants can also be glidants
What is the purpose for wetting agents and surfactants?
2-4%, if API is hydrophobic, these improve wettability and facilitate dissolution
What is the purpose for coating?
- Ease of swallowing
- Protection
- Taste masking
- Aesthetics
List advanced uses of excipients
- Enhancement of oral absorption
- Enhancement of absorption sites other than oral
- Drug targeting
- Manufacturing process aids
