Liquid Dosage Forms

-Easier to swallow -Faster absorption -Reduced irritation -Homogeneous system (No dose variation) Advantages of oral solutions? -Growth of microorganisms -Shorter shelf lives -Dose accuracy (requires the use of a What are the disadvantages of oral soluspoon/syringe tions? -Taste -Expensive to ship -Harder to manufacture and transport What is the most common co-solvent in liquid dosage forms? Glycerol What is the purpose of co-solvents in liquid dosage forms? Increase solubility Apart from glycerol, what co-solvents are commonly used in liquid dosage forms? -Alcohol USP -Propylene Glycol USP -PEG (polyethylene glycol) How is drug solubility increased in liquid dosage forms, apart from co-solvency? Surface-active agents What are the three things that excipients can be used for in liquid dosage forms (other than solubility)? 1) Buffers 2) Sweetners 3) Viscosity-enhancing agents What is the role of antioxidants in liquid dosage forms? -Increases stability -Reduces degradation via inhibition of radical-induced decomposition 1)Chemically stable over the shelf life of What 3 things must preservatives be in the product order to be considered for liquid dosage 2)Broad spectrum of antimicrobial activiforms? ty 3)Low toxicity What is the role of preservatives in liquid dosage forms? 1/6 Reduce microbial activity What are the three main factors that affect the efficacy of preservatives in oral solutions? 1) pH 2) Presence of micelles 3) Presence of hydrophilic polymers How do acidic preservatives work? -Unionised acid diffuses across the outer membrane of microorganisms -Once it has entered the cytoplasm it then dissociates and causes acidification of the cytoplasm To stop early dissociation of acidic Why is the pH of the formation important preservative before it has entered the in acidic preservatives? microorganism -Lipophilic preservatives may partition Why does the presence of micelles often into the micelle lead to decreased efficacy of preserva-This causes a decreased concentration tives? of free micelles -Preservative interacts with hydrophilic Why does the presence of hydrophilic polymers polymers often lead to decreased effica-Similar to micelles where it decreases cy of preservatives? the free concentration of preservative What separates a syrup from a solution? Syrups contain a larger amount of sugar so are more viscous What separates an elixir from a solution? An elixir contains alcohol as a solvent What are the two main reasons that par- 1) Ionisation ticles acquire charge following disper2) Adsorption of ions (causing the elecsion? trical double layer effect) What is the name for the metric used to measure the potential of the electrical double layer? Zeta potential 1) No interaction What are the three different states of in- 2) Coagulation (will not break apart upon teraction between particles in a solution? shaking) 3) Flocculation (loosely aggregated? In DVLO theory what is the balance of separation between? Between attractive van der Waals surfaces and repulsive forces driven by electrical repulsion (zeta potential) 2/6 What is sedimentation? Drug particles sinking to the bottom What is caking in suspensions? -Once sedimentation occurs -The weight of the drug can cause irreversible interactions that are known as caking What is a suspension? heterogeneous mixture What are the main disadvantages of oral suspensions? -May not have uniform distribution -Unstable -Aesthetic suspensions are difficult -Bulky -Particle size What are the two main formulation con-Wetting properties (poor wetting leads siderations for suspension making? to aggregation) How do hydrophilic polymers affect crystal growth? Decrease How else can crystal growth be controlled other than hydrophilic polymers? Temperature cycling (freeze-thaw cycles) Why is crystal growth in suspensions bad? -Less uniform dosage -Increased particle size -May cause sedimentation How does the addition of electrolytes affect flocculation? -Reduction in zeta potential -Decreases flocculation 1)Increase wetting of particles What is the main reasons we use surfac2)Aid dispersion reducing aggregation tants in oral suspensions? and increase flocculation Out of ionic and non-ionic surfactants which are preferred? Non-ionic as they are less toxic How do hydrophilic polymers aid viscosity? Increase How do hydrophilic polymers aid sedimentation? Decrease What are the majority of hydrophilic polymers in oral suspensions? Cellulose derivatives 3/6 What are the two main ways to make oral suspensions? -Direct incorporation -Precipitation How does the direct incorporation method work? -Solute is added into solvent and mixed -High-speed mixing is used -Particle size is important so milling may be needed first What are the two phases of emulsions? Disperse and continuous What is the continuous phase? Phase in which disperse phase is distributed (solvent) What is the disperse phase? The phase that is sub-divided (solute) What are the main uses for emulsions? -Creams -Parenteral nutrition -Oral administration -Rectal -Delivery of drugs with low aqueous solubility -Taste masking What are the advantages of pharmaceu-Administration of oils with therapeutic tical emulsions? effect -Swallowing issues -Reduction in irritation What is miscibility? The ability to mix without separating into two states (formation of a homogeneous mixture) What are the disadvantages of pharmaceutical emulsions? -Thermodynamically unstable -Manufacturing difficulties Are oil and water miscible or immiscible? Immiscible Are oil-in-water emulsions miscible with oil? No Are oil-in-water emulsions miscible with water? Yes Are water-in-oil emulsions miscible with oil? Yes No 4/6 Are water-in-oil emulsions miscible with water? Do oil-in-water emulsions conduct electricity? Yes Do water-in-oil emulsions conduct electricity? No -Complete coalescence (clumping) of the internal phase -Resulting in separation of the emulsion into two layers What is cracking in emulsions? Is cracking reversible? No What is cracking usually due to? -Incorrect emulsifying agents -Temperature -Presence of incompatible agents -Microbial spoilage What is the role of mono/multilayer film at the interface between droplet and external phase? Prevents coalescence What causes cracking in an emulsion? Destruction of the mono/multilayer between droplets Is flocculation reversible? Yes What is creaming in emulsions? Rise of dispersed particles to the top of an emulsion Is creaming reversible? Yes What equation dictates the rate of creaming? Stokes What is the ideal density difference between the two phases? Zero 5/6 -Reduce particle size of dispersal phase What are methods by which the rate of (remain homogeneous) creaming can be reduced? -Increase viscosity (harder to separate) What is phase inversion in emulsions? Swapping of o/w to w/o and vice versa -Form a steric barrier reducing coalesHow does the addition of adsorbed parti- cence cles increase the stability of emulsions? -Reduces zeta potential decreasing chance for coagulation -Form a film around the dispersed droplets -Reduces interfacial tension -Reduces aggregation What is the role of emulsifying agents? 6/6