Phcy 512 Exam 1 PDF

512 EXAM 1 Class 01- Pharmaceutics 101 Compare pharmaceutics and biopharmaceutics, including their focus areas, methodologies, and importance in drug development and patient care. ​ Pharmaceutics: the study of physical and chemical properties of drugs related to dosage form design and ma...

512 EXAM 1 Class 01- Pharmaceutics 101 Compare pharmaceutics and biopharmaceutics, including their focus areas, methodologies, and importance in drug development and patient care. ​ Pharmaceutics: the study of physical and chemical properties of drugs related to dosage form design and manufacturing ○​ Goal of drug delivery: ​ Right drug target ​ Right amount of active ingredient ​ Right amount of time ​ Desired pharmacological outcome ​ Biopharmaceutics: application of physical chemistry and dosage form science to drug stability, delivery, release, disposition, pharmacokinetics, therapeutic effectiveness, and the development of quality standards for drug products ○​ Applied science that examines the relationship between: ​ Physical and chemical properties of a drug in a dosage form ​ Biological fate of a drug ​ Observed biological response Differentiate the two primary branches of pharmacology: pharmacodynamics (PD) and pharmacokinetics (PK). ​ Pharmacodynamics: what a drug does to the body ​ Pharmacokinetics: what the body does to a drug Analyze the significance of the LADME drug disposition processes to pharmacotherapy (include concept of first-pass metabolism). ​ Liberation: drug released from dosage form ​ Absorption: drug into systemic circulation ○​ After absorption, some % of lipophilic drug undergo first-pass metabolism and are immediately metabolized and excreted before they are distributed throughout the body ​ Distribution: drug delivered to tissues/organs throughout the body ​ After distribution ○​ Can go to site of action and do its job ○​ Can be excreted if the drug is hydrophilic ○​ Can be metabolized and then excreted if the drug is lipophilic Explain the qualities of an ideal dosage form. 1.​ One dose in a manageable size unit 2.​ Palatable or comfortable 3.​ Convenient and easy to use 4.​ Stable 5.​ Release of drug Describe common dosage forms for oral drug administration, including powders, tablets, capsules, solutions, and suspensions. ​ Powder ○​ Fine, solid particles ○​ May be composed of only the active ingredient OR may be a mixture of active and inactive ingredients ​ Tablet ○​ A compressible vehicle is blended with the medicinal agent, and if necessary, with a lubricant and a disintegrant, and then the blend is compressed ​ Capsule ○​ Gelatin shells filled with the ingredients that make up an individual dose ○​ May contain dry powders, semi-solids, or liquids that do not dissolve gelatin ​ Solution ○​ Homogeneous one-phase system composed of 2 or more components, one of which is completely dissolved in the other and dispersed throughout the solvent in molecular or ionic sized particles ​ Suspension ○​ Two-phase system consisting of a finely divided solid disperse (suspended) in a liquid (the dispersing medium) Explain the major physiological barriers to oral drug delivery. ​ Physical ○​ Cells, cell membranes, fluid between cells, mucus, etc ​ Biochemical ○​ Environmental factors (pH) ○​ Enzymatic degradation ○​ Microbial metabolism Explain the mechanisms of drug absorption across a biological membrane including cellular diffusion, transport, and endocytosis. ​ Passive transport: the movement of molecules across a cell membrane from an area of higher concentration to an area of lower concentration ○​ Paracellular: the movement of substances between cells across a tight junction ○​ Transcellular: the movement of substances through the cells ​ Active transport by carrier proteins (endocytosis/transcytosis) ​ Active transport by protein channels ​ Micropinocytosis followed by non-specific transcytosis Explain the concept of bioavailability in the context of drug disposition, including its relationship to the LADME processes and its importance in achieving therapeutic effects. ​ The proportion of drug that is absorbed and reaches systemic circulation ​ The rate and extent to which a drug is absorbed from a dosage form and becomes available at the site of drug action ​ It depends on various physicochemical and physiological factors that affect the liberation,  absorption, distribution, metabolism, and excretion of the drug ​ If you have low bioavailability, then there won’t be much to distribute throughout the body Describe common routes of drug administration, including the administration locations. ​ Oral ○​ Administration location: oral cavity ○​ Primary absorption site: epithelium of the small intestine ​ Intravenous (IV) ○​ Administration location: veins ○​ Primary absorption site: directly enters bloodstream ​ Corneal (ocular) ○​ Administration location: eye surface ○​ Primary absorption site: corneal epithelium (main route of lipophilic drugs); conjunctiva and sclera (non-corneal route, especially for hydrophilic drugs) ​ Transdermal ○​ Administration location: epidermal (skin) surface ○​ Primary absorption site: stratum corneum and capillaries ​ Nasal ○​ Administration location: nasal cavity ○​ Primary absorption site: nasal epithelium ​ Vaginal ○​ Administration location: vaginal cavity ○​ Primary absorption site: vaginal epithelium Identify the biological absorptive membrane for alternative routes of delivery. ​ Corneal → cornea ​ Transdermal → skin ​ Nasal → nasal epithelium ​ Vaginal → vaginal epithelium Class 02 – Physicochemical Properties of Solutions; Drug Partitioning, Flux & Absorption Calculate and convert between different units of concentration, including mEq and osmolarity ​ Molarity: mol/L or mmol/L ○​ Number of molecules, ions, or atoms ​ Equivalency: Eq/L or mEq/L ○​ Total number of positive or negative charges in solution (but not both) ○​ # molecules x total # positive or negative ions per molecule ​ Osmolarity: Osm/L or mOsm/L ○​ Total number of particles (including molecules and ions) ○​ # molecules x # particles generated per molecule Discuss the relevance of osmolarity, milliequivalence and tonicity concepts in pharmacy practice Describe the colligative properties of solutions and osmosis ​ Properties that rely on the number of particles of solute and solvent rather than the nature of the solute and solvent ​ As more of a solute is added to solvent, certain properties of that solution will change ​ The four colligative properties of solution are ○​ Vapor pressure lowering ○​ Freezing point depression: the freezing point of a solvent is lowered when a non-volatile solute is added to it ○​ Osmotic pressure ○​ Boiling point elevation: increase in the boiling point of a solvent when a non-volatile solute is added to it Calculate isotonicity using the NaCl equivalent method to prepare isotonic solutions Describe how thermodynamics of a solution affects stability by understanding Gibb's free energy, enthalpy, and entropy ​ Enthalpy (deltaH): total heat contained within a system ○​ deltaH < 0 : reaction releases energy - exothermic ○​ deltaH > 0 : reaction requires energy - endothermic ​ Entropy (deltaS): measures the disorder in a system ○​ deltaS > 0 : increasingly disordered, more favorable ○​ deltaS < 0 : increasingly ordered, less favorable ​ Gibb’s free energy: measures possibility for a process to occur ○​ deltaG = deltaH - T*deltaS ○​ DeltaG < 0 : reaction will occur spontaneously ○​ deltaG = 0 : at equilibrium ○​ deltaG > 0 : reaction will not occur spontaneously Explain the thermodynamics of dissolution ​ Three stages of dissolution ○​ Break solute-solute attractions and break solvent-solvent attractions (usually endothermic) ○​ Form solute-solvent attractions (usually exothermic) ​ Endothermic heat of solution means deltaH > 0, which is unfavorable for a spontaneous reaction ​ Since dissolution occurs spontaneously (without adding additional energy), delta G is < 0 ​ deltaS must be positive, so the reaction must go to a more disordered state, increased entropy of the system ​ Increasing temperature increases molecular motion, which creates more disorder (increases entropy) Understand partition coefficient and its relationship to lipophilicity ​ The more lipophilic the drug, the greater the partition coefficient ​ Ratio of drug in organic phase (lipophilic) to drug in aqueous phase (hydrophilic) Explain the relationship of the partition coefficient to HLB and permeability ​ Relates how easily drug will go into hydrophobic area (e.g. lipid tail area of membrane) versus hydrophilic area (e.g. outside membrane) ​ logD pH dependent version of log P ​ How does logD relate to drug permeation? ○​ Inverted U shape curve Explain how pH can affect the apparent partition coefficient and membrane permeability of ionizable drugs ​ pKa ○​ How weak or strong an acid is ○​ Will tell you how ionized a drug is and therefore how likely a drug will diffuse through a membrane ​ A highly ionized drug will not pass easily through a membrane ​ Apparent PC versus intrinsic PC ○​ Intrinsic (degree symbol) = [HA]o/[HA]w → non-ionized species in both layers ○​ Apartment (apostrophe) = [HA]o/[HA]w + [A-]w → ionized species in the aqueous layer ○​ Be able to know which will be larger at a given pH Describe the relationship between partition coefficient and permeability ​ How does logD relate to drug permeation? ○​ Inverted U shape curve ​ Drugs with logP of 1-3 are sweet spot and are permeable ​ If go above that then they are too lipophilic and get stuck in the membrane ​ If below that then they are too hydrophilic and don’t want to go into the fatty membrane Calculate partition and distribution coefficients ​ Ratio of non-ionized species’ concentrations in the organic and aqueous layers ​ logP = log of the partition coefficient ○​ Sometimes appears as logKo/w ​ logD = log of the distribution coefficient ○​ Partition coefficient as a specific pH  ​ ​ Explain the importance of drugs' abilities to partition into non-biological membranes and surfaces Define Fick's Law and explain the processes of diffusion and flux ​ Fick’s law relates the diffusive flux of a solute to the concentration gradient ​ J is the diffusive “flux”, in units of mass (M) per time (t) per area (A) ​ D is the diffusivity, or diffusion coefficient, in units of area per time Use Fick's Law to calculate diffusion rate and flux. ○​ Diffusion rate: ○​ Flux: Explain how factors of the Stokes-Einstein equation impact the diffusion coefficient ​ Used to determine diffusion coefficient for Fick’s Law  ​ Use the Higuchi Equation to calculate the amount of drug released from a drug delivery system with artificial membranes Class 03 – Drug Stability Describe the role of kinetics in drug stability and degradation ​ Kinetics is rate at which a drug is degraded or eliminated from the body Define drug product stability ​ The extent to which a dosage form retains the same properties and characteristics that it possessed at the time of its manufacture ○​ Within specified limits ○​ Throughout its period of storage and use Describe the five types of product stability recognized by the USP ​ Chemical: each active ingredient retains its chemical integrity and labeled potency ​ Physical: original physical properties (including appearance, palatability, uniformity, dissolution, and suspendability) ○​ Polymorphs ​ Differ in solubility, compressibility, melting point, appearance, etc ​ Melting and cooling semisolids ○​ Formation of eutectic mixture ○​ Crystallization ​ Different particle size distributions affects appearance, uniformity, dissolution, and/or suspendability  ​ Larger particles formed when cycling between increased and decreased temperatures ○​ Vaporization ​ Higher concentration of dissolved or suspended drug in liquid preparations when water evaporates ○​ What properties of a drug would make it volatile? ​ Low molecular weight ​ Log P > 1 (lipophilic) ​ Microbiological: sterility or resistance to microbial growth is retained according to specified requirements ​ Therapeutic: the therapeutic effect remains unchanged ​ Toxicological: no significant increase in toxicity occurs ​ If physical, chemical and microbiological stabilities are maintained, therapeutic and toxicological stabilities are almost always ensured Contrast the major drug degradation reactions that lead to chemical product instability ​ Hydrolysis ○​ Chemical reaction with water - most commonly occurs in molecules with esters, lactones ○​ Solvolysis can occur in preparations with nonaqueous solvents or vehicles ​ Oxidation ○​ Addition of oxygen or removal of hydrogen ○​ Susceptible groups: double bonds, halogenated hydrocarbons ○​ Auto-oxidation: uncatalyzed reaction of a drug with O2 ○​ Radical chain mechanism ○​ Characterized by change in color, precipitation, or odor ○​ Often more likely to occur when ​ In aqueous environment ​ Exposed to oxygen (ROS) ​ Exposed to light (photo-induced oxidation) ​ Catalyzed by trace amounts of metals ​ At high pH (some oxidation reactions are base-catalyzed) ​ Photodegradation ○​ Usually indicated by a change in color of drug or solution ○​ Usually occurs when drug is removed from manufacturing packaging and placed in new environment ○​ Preventable by packaging in light-resistant or opaque containers that exclude UV light (amber glass excluded light < 470 nm) ○​ Primary photochemical reactions occur when the wavelength of incident light is within the wavelength range of absorption of the drug ○​ Photons from UV light have enough energy to induce formation of a free radical or another reactive intermediate ○​ Photosensitizing excipients may absorb light and indirectly transfer the absorbed energy to a drug  ​ Isomerization Explain the methods to slow each major drug degradation process ​ Methods to prevent hydrolysis ○​ Reduce or eliminate water from formulation ○​ Protect solid dosage form from humidity ○​ Refrigerate to slow rate of hydrolysis ​ Methods to prevent oxidation ○​ Antioxidants ○​ Protect from light ○​ Airtight ○​ Add a chelating agent to bind metals ○​ Buffer the system if base catalyzed ​ Methods to prevent photodegradation ○​ Preventable by packaging in light-resistant or opaque containers that exclude UV light (amber glass excluded light < 470 nm) List storage factors that affect drug stability ​ Exposure to light, air, humidity List manufacturing, packaging, and storage methods used to reduce each type of product instability Explain the relationship between temperature and reaction rate ○​ ○​ Temperature speeds up reaction → increasing temperature leads to: ​ Increase in number of collisions ​ Increase in reaction rate ○​ Rule of thumb: 10 degrees gives 2-3 fold rate increase Explain the utility of accelerated stability testing ​ Quick detection of drug degradation ​ Prediction of shelf-life ​ Rapid quality control ​ Focuses on ○​ Moisture and humidity (hydrolysis) ○​ Light/UV (photodegradation)  ○​ Temperature Use the Arrhenius equation to explain the effect of temperature on reaction rate ​ The relationship between the rate of reaction and the temperature ​ Explain how the Arrhenius equation can be used to predict drug stability ​ Can change temperature in the equation to see how the rate of reaction will change Class 04 – Chemical Kinetics Describe the role of kinetics in drug stability and degradation Determine the order of reaction for zero- and first-order reactions. ​ Zero-order reactions: concentration decreases by constant amount - linear concentration vs time plots ​ First-order reactions: concentration decreases by constant fraction - exponential decay concentration vs time plots Differentiate between zero-order, first-order, second-order, and pseudo-first order kinetics ​ Zero-order: rate is constant and independent of concentration of reactant ​ First-order: rate is concentration dependent on one reactant ​ Second-order: rate is concentration dependent on two reactants or the square of the concentration of one reactant ​ Pseudo-first order: rate is concentration dependent on two reactants, but the concentration of one reactant is so much larger than the other or one of the reactants is constant, so it appears as first-order Calculate the rate of reaction for zero- and first-order reactions.  Order Zero First Second d[A]/dt (±) k k·[A] k·[A]2 integrated rate [A]t = [A]0 – kt [A]t = [A]0 ·e–kt 1/[A]t = 1/[A]0 + kt law ln([A]t) = ln([A]0) – linear form (same) (same) kt half-life t1/2=[A]0/2k t1/2 = 0.693/k t1/2=1/k[A]0 Explain xf-life ​ the duration of time during which at least 90% of the original drug is expected to remain unchanged Explain expiration date ​ date given by the manufacturer guaranteeing full potency of drug - usually 90% of API Calculate first order shelf-life ​ t90% = 0.1054/k Calculate half-life, concentration, shelf-life, and expiration date. ​ Zero order reaction ○​ t1/2 = 0.5[A]0/k = [A]0/2k ○​ t90% = 0.1[A]0/k ​ First order reaction ○​ t1/2 = 0.693/k ○​ t90% = 0.1054/k Differentiate between simple and complex reaction mechanisms. ​ Complex: pseudo-first order kinetics Explain the importance of first-order kinetics in pharmacy. ​ Almost all drug degradation reactions and elimination processes exhibit first-order kinetics Discuss the hydrolytic degradation of drugs. ​ Functional groups that are readily hydrolyzed  ○​ Most commonly occurs in chemicals with reactive carbonyl groups (esters, lactones, etc) ○​ Phosphates (especially via phosphatases) ○​ Epoxides (acid or base catalysis) ○​ Should be able to recognize the 8-10 common functional groups that he gave that are susceptible to hydrolysis ​ Role of hydrolysis in drugs ○​ Can be a mechanism of degradation ○​ Can reveal an active compound from a prodrug Class 05 – Acid-Base Concepts of Drugs & Molecular Interactions Identify common functional groups and their charge in biological conditions Classify drugs as acidic or basic Explain how a drug's pKa influences its solubility and absorption properties ​ Drug can only be absorbed if its in an aqueous solution, but non-ionized drug crosses lipid membranes more readily ​ Acidic urine pH results in more ionization and increased renal elimination (because ionized cannot be reabsorbed → not lipid soluble) ​ Alkaline urine pH results in less ionization and decreased renal elimination ​ For both acids and bases, charged species have greater aqueous solubility but poorer lipid permeability than uncharged species ​ For acid: uncharged = HA, charged = A- ​ For base: uncharged = B, charged = BH+  ○​ pH < pKa pH = pKa pH > pKa lower pH [ionized] = higher pH higher [H+] [non-ionized] lower [H+] [protonated] > [deprotonated] > [deprotonated] [protonated] for [HA] > [A–] [A–] > [HA] [HA] = [A–] acid: [non-ionized] > [ionized] [ionized] > [non-ionized] ⇧ lipid permeability ⇩ H2O ⇧ H2O solubility ⇩ lipid solubility permeability [protonated] > [deprotonated] > [deprotonated] [protonated] for [BH+] > [B] [B] > [BH+] [HB+] = [B+] base: [ionized] > [non-ionized] [non-ionized] > [ionized] ⇧ H2O solubility ⇩ lipid ⇧ lipid permeability ⇩ H2O permeability solubility ○​ Calculate fraction of ionized or non-ionized drug at a given pH ○​ ○​ ○​  ○​ Describe zwitterions ​ Molecules having both positive and negative charges ​ pI = pH where net charge is zero ○​ pKa1 + pKa2/2 Apply the Henderson-Hasselbalch and Van Slyke equations to calculate properties of buffer solutions ○​ When pH < pKa, a molecule is protonated ○​ ○​ Salts of acidic drugs have positive counterions ○​ Salts of basic drugs have negative counterions  ○​ ○​ Using Henderson-Hasselbalch Eqn to calculate pH ○​ Differentiate among different types of intermolecular interactions. ○​ Covalent 40 – 140 Drug-polymer complex Drug-receptor complex Ionic 5 – 10 Organic ion pair Hydrogen 1–7 —R-O-H ⋅⋅⋅ O=C< Ion-dipole 1–7 Coordination compounds  Drug-protein / Drug-polymer Hydrophobic 1 Inclusion complexes Apply the concept of surface energy to differentiate between adhesion and cohesion ​ Adhesion is the attraction between molecules of [same/different] substances ​ Cohesion is the attraction between molecules of [same/different] substances Apply the concept of surface energy to differentiate between absorption and adsorption ​ Absorption is the process of a substance being dissolved into another substance, while adsorption is the process of a substance sticking to the surface of another substance Differentiate different types of complexes based on the intermolecular forces involved: cyclodextrins, ion-exchange resins, chelators ​ Ion exchange resins ○​ Ion exchange resins rely on an adsorption phenomenon involving electrostatic forces between the solute (e.g., drug) and the resin ○​ Application ​ Taste making ​ Sustained release/rapid dissolution ​ Stability ​ Powder processing aid ​ Cyclodextrins ○​ Cyclic oligosaccharides ○​ Hydrophilic exterior ○​ Hydrophobic interior ○​ Form complexes with hydrophobic drugs, increasing their solubility ​ Chelating agents ○​ Chelator, central metal atom Explain the chelate effect ​ Enhanced stability of chelating ligands for a metal ion compared to the stability of a collective of similar non chelating (monodentate) ligands for the same metal Explain the macrocyclic effect. ​ The macrocyclic effect is the increased stability of coordination compounds formed by large, cyclic ligands. This effect is due to the high affinity of metal cations for macrocyclic ligands Explain how complexation can lead to drug instability or adverse clinical effects. Class 06 – Drug Dissolution & Solubility Describe the process of API liberation from oral dosage forms ​ Dissolution: solid into solvent ○​ Kinetic process quantified by its rate ○​ Amount of solid substance that goes into solution per unit time ​ Liberation from solid = disintegration + dissolution ○​ Disintegration ​ Breaks down substances into tiny granules or particles ​ Increases surface area ○​ Dissolution ​ Substance goes into solution ○​ Importance: ​ Potentially a rate-limiting step → dissolution is often the rate limiting step Calculate drug dissolution rates using the Notes-Whitney equation ○​ ○​ Explain the difference between sink and non-sink conditions ○​ Non-sink conditions: normal conditions → first order dissolution ○​ Sink conditions: Cs > 10 Cb → zero order dissolution under sink conditions ​  ○​ Explain common strategies to enhance drug dissolution rate ○​ Particle size reduction ​ The rate of drug dissolution is often intrinsically related to drug particle size ​ Smaller particle size → the surface area to volume ratio increases ​ The larger surface area allows greater interaction with the solvent which causes an “increase in solubility” (increasing the rate of dissolution not intrinsic solubility) ​ Methods to reduce particle size ​ Micronization ​ Nanosuspension ​ Sonocrystalization ​ Supercritical fluid process ​ Spray-dryings ○​ Co-solvent addition ○​ Prodrug ○​ Surfactant addition ○​ pH modification ○​ Emulsions ○​ cyclodextrins Recognize the USP tests for disintegration and dissolution Explain the importance of solubility for drug formulations for various routes of administration Classify drugs using the USP terms "very soluble", "slightly soluble", and "insoluble" ○​ Term Solubility Very soluble > 1 g/mL Freely soluble 1 g/mL – 100 mg/mL  Soluble 100 mg/mL – 33 mg/mL Sparingly soluble 33 mg/mL – 10 mg/mL Slightly soluble 10 mg/mL – 1 mg/mL Very slightly soluble 1 mg/mL – 0.1 mg/mL Insoluble < 0.1 mg/mL Classify drugs using the Biopharmaceutical Classification System ○​ ○​ High Solubility: when the highest dose strength is soluble in less than 250 mL over a pH range of 1.0 – 7.5 ​ Dose volume = dose/solubility → needs to be < 250 mL ○​ High permeability: > 90% of dose is absorbed ​ Amount absorbed/dose amount x 100 → needs to be > 90% Estimate drug solubility using the General Solubility Equation (GSE) ○​ Solubility ​ Thermodynamic ​ State of dynamic equilibrium reached when rate of dissolution equals the rate of precipitation ​ Maximum amount of the solute dissolved in a given solvent  ○​ ○​ GSE Calculate the solubility product (Ksp) for drug salts ​ K = [Ag+][Cl-]/[AgCl] ○​ AgCl is a solid, so no concentration ​ Ksp = [Ag+][Cl-] ​ Ksp indicates the degree to which a salt compound dissociates in water → higher Ksp = higher solubility Explain the common ion effect ​ A shift in solubility when a compound containing an ion already in solution is added to the solution Explain common strategies to enhance the solubilization of drugs ​ pH adjustment ○​ As pH increases, the solubility of basic drugs generally decreases ○​ As pH increases, the solubility of acidic drugs generally increases ​ Formation of salts ○​ Two major competing factors ​ Lattice energy - measure of energy released when ions are combined to make a compound ​ Solvation enthalpy - energy released when ions interact with water molecules ​ Formation of hydrates, solvates, or co-crystals ○​ Co-crystals increased solubility ​ Use of co-solvent ○​ Need to be careful of toxicity of the co-solvent ​ Complexation (e.g., cyclodextrins) ○​ Pros: increase solubility, stabilize compounds, prevent early metabolism  ○​ Cons: expensive, nephrotoxicity ​ Prodrug approach ​ Use of surfactants (e.g., emulsions) ○​ Emulsion: fine dispersions of droplets of one liquid in another (immiscible) Class 07 – Pharmaceutical Solids Define “micromeretics” and describe what it entails ​ Micromeretics: the study of particle properties like size, shape, surface area, and flow, critical for drug formulation and performance ​ Affects: drug release, dissolution, and absorption, physical stability (suspensions), dose uniformity Describe the factors that affect the flow properties of powders ​ Flowability: the ability of powder particles to move or flow freely and predictably ○​ Many factors can impact the flowability of a powder including: particle size and distribution, particle shape (spherical particles flow better than needle-shaped particles), surface roughness, moisture content, density, cohesive properties, hygroscopy Identify and describe the structure and properties of microporous, mesoporous, and macroporous particles ​ Micropores: Less than 2 nanometers in diameter, examples include zeolites and activated carbon ​ Mesopores: Between 2 and 50 nanometers in diameter, examples include mesoporous silica and activated carbon ​ Macropores: Greater than 50 nanometers in diameter, examples include sintered metals and ceramics ​ Porous solids have high specific surface areas and pore volumes, while non-porous solids have low specific surface areas and pore volumes Identify the eutectic point on a phase diagram and discuss its impact on drug manufacturing ​ The eutectic point is the lowest temperature at which a mixture of two or more solid substances melts into a liquid ​ At this point, the mixture behaves like a single compound and melts completely, even if the individual substances have higher melting points on their own ​ The eutectic point can impact drug manufacturing and drug release ​ On a phase diagram, the eutectic point is found at the intersection of melting point curves Describe how contact angle is used to measure wettability of a solid ​ Wettability is the ability of a solid surface to come into contact with and be wetted by a liquid ​ It is a critical property influencing how well a liquid spreads over a solid surface ​ Contact angle is used to measure wettability. A lower contact angle generally implies better wettability. Define “sublimation” and why it makes some powders hazardous to handle ​ Sublimation is the direct transition from the solid phase to the vapor phase, skipping the liquid phase ​ Some powders that can sublimate are hazardous because they can be difficult to handle and may cause issues with dosing and safety. Examples include camphor and radioactive iodine-131. Explain the role of excipients in tablet and capsule manufacture ​ Excipients are inactive substances included in tablets and capsules that facilitate drug formulation, stability, delivery, and manufacturability ​ Types of excipients include: ○​ Antiadherents: prevent sticking to tablet punches (e.g., magnesium stearate) ○​ Glidants: promote powder flowability (e.g., fumed silica, talc, magnesium carbonate) ○​ Lubricants: reduce friction between particles (e.g., talc, silica, magnesium stearate) ○​ Fillers/Diluents: add bulk to the formulation (e.g., dibasic calcium phosphate, lactose, sucrose) ○​ Binders: help hold the tablet together (e.g., sucrose, lactose, starches, cellulose, sorbitol) ○​ Disintegrants: help the tablet break apart in the body (e.g., sodium carboxymethylcellulose, methylcellulose, polyvinyl pyrrolidone) ○​ Antioxidants & Preservatives: prevent degradation of the drug (e.g., Vitamin E, methyl/propyl paraben) ○​ Coatings: protect the tablet and aid in swallowing (e.g., hydroxypropyl methylcellulose) ○​ Coloring Agents, Sweeteners, Sorbents: enhance appearance and mask taste (e.g., moisture-proofing agents) Compare and contrast the differences between hard and soft gelatin capsules ​ Hard gelatin capsules are typically used for powders ​ Soft gelatin capsules are typically used for oils ​ The basic component of both is gelatin, but soft gelatin shells are plasticized, making them softer ​ The ratio of dry plasticizer to dry gelatin determines the hardness of the soft gelatin shell. Ratios vary from 0.3-1.0 for very hard shells to 1.0-1.8 for very soft shells ​ Soft gelatin capsules may include up to 5% sugar to give a "chewable" quality ​ The residual shell moisture content of finished soft gelatin capsules is 6-10% Know the definitions of various morphologies including amorphous, crystal, polymorphs, solvates, hydrates, salts, and co-crystals. Be able to explain which physiochemical properties of drugs can be impacted by morphology. ​ Morphology refers to the physical form, structure, and surface characteristics of the particles that make up a solid material ​ It significantly influences a material’s behavior in pharmaceutical processes and drug delivery performance ​ The morphology of a drug can impact its solubility, dissolution, melting point, stability, hardness, hygroscopicity, color, and refractive index ​ Amorphous forms: Solids that do not have a distinctive powder X-ray diffraction pattern. They are generally less stable than crystal forms and may convert to crystal over time. They typically have better solubility, lower melting points, are more readily compressible, and have faster dissolution than crystal forms ​ Crystal forms: Solids where the individual particles that make it up are in an orderly arrangement ○​ Polymorphs: Different crystal structure forms in which a compound can crystallize ○​ Solvates: Crystal structures incorporating solvent molecules ○​ Hydrates: Crystal structures incorporating water molecules ○​ Salts: The product of the reaction of an acid and a base ○​ Co-crystals: Crystals containing two components that are not a salt ​ A drug's morphology can change over time due to environmental, physical, and chemical factors.... For example, amorphous forms may convert to crystal forms over time Class 08 – Interfacial Phenomena and Surfactants Define surfactant and describe the structure and function of various types of surfactants ​ Surface active agents ​ Surfactants are amphiphilic molecules consisting of hydrophobic and hydrophilic regions ​ They bridge the gap at interfaces, reducing surface tension and stabilize mixtures that would otherwise fully separate ​ Describe the structure and function of various types of surfactants ○​ Anionic: negatively charged head groups ​ Unstable: charges on the head groups will repel each other  ○​ Cationic: positively charged head groups ​ Unstable: charges on the head groups will repel each other ○​ Nonionic: no charge but hydrophilic head groups ○​ Zwitterionic: both positive and negative charged head groups Explain the concept of surface tension ​ Molecules in a liquid’s bulk experience equal attractive forces from all directions. ​ Molecules at the surface, however, experience stronger cohesive forces from below (since there are no liquid molecules above them). ​ This creates an inward force, making the surface molecules more tightly packed and causing the liquid to minimize its surface area. Define hydrophilic-lipophilic balance and categorize surfactants using the HLB system ​ The hydrophilic-lipophilic balance (HLB) is a measure of how hydrophilic a surfactant is. It is calculated from the weight percentage of the hydrophilic groups to the hydrophobic groups in a molecules, with values ranging from 1-20 ​ HLB 12-18: water-soluble surfactants for oil-in-water emulsions ​ HLB 8-12: intermediate surfactants ​ HLB 3-8: oil-soluble surfactants for water-in-oil emulsions ​ Describe the structure and key factors in formation of surfactant aggregates (e.g., micelles) ​ Micelles form when the concentration of surfactant is high enough that the air-liquid interface is full ​ Forces driving micelle formation: hydrophobic force and entropy ​ Forces opposing micelle formation: concentration gradient, thermal motion, charge repulsion between ionic polar heads ​ Surfactant behavior in water ○​ Low concentration: surfactants dissolve as individual molecules ○​ Increasing: accumulate at surface ○​ CMC: surface becomes saturated with surfactant molecules ○​ Above CMC: micelles form Define critical micelle concentration (CMC) and how it relates to pharmaceutical design  ​ CMC = surfactant concentration where micellization occurs ​ No change in surface tension once you reach the CMC ​ Determined looking at the surface tension ○​ Low surface tension if lots of surfactants - surfactants break up bonding energy of water at the surface ○​ ○​ Measure change in surface tension vs concentration ​ DuNuoy Ring ​ Wilhelmy Plate ​ Factors affecting CMC and micellar size ○​ Hydrophobic group: increasing chain length results in decreased CMC and increased micelle size ○​ Hydrophilic group: nonionic micelles have lower CMC than their ionic counterparts ​ No ‘electrical work’ required in process of formation ​ CMC increases with increase in chain length of polyoxyethylene chain ​ May be asymmetric (ellipsoidal) ○​ Nature of counterion ​ The more weakly hydrated the counterion, the larger the micelles ​ Micelle size increases with increasing atomic weight of counterion ​ Cationic micelles: Cl- < Br- < I- ​ Anionic micelles: Na+ < K + < Cs+ ○​ Addition of electrolytes: decreases CMC and increases micelle size Class 09 – Pharmaceutical Dispersions