Pharmaceutics & Drug Delivery Systems Summary (PDF)

Key Concepts To Understand For Pharmaceutics and Drug Delivery Systems Solid changes to liquid (fusion), liquid to solid (solidification), liquid to gas (vaporization), gas to liquid (condensation) If solid goes directly to gas (sublimation), gas to solid (deposition...

Key Concepts To Understand For Pharmaceutics and Drug Delivery Systems Solid changes to liquid (fusion), liquid to solid (solidification), liquid to gas (vaporization), gas to liquid (condensation) If solid goes directly to gas (sublimation), gas to solid (deposition) Van der waals: weakest bonds between uncharged molecules; 2 types: ○ London forces: temporary dipoles where weak bonds and molecules are uncharged ○ Dipole-dipole: weak interactions but not temporary where one side is always negative and the other is positive (note: dipole-dipole bond can exist between two alcohols) Van Der Waals Forces - Weak electric Forces. F2/I2 halogens < Hydrogen bonds - b/w H atoms and electronegative atoms F,O,N. e.g; H2O < Metallic Bonding - Sharing of electrons in a lattice cations. e.g, Iron < Electrostatic Bonding - One ion donates electrons to another ion. e.g, NaCl < Covalent Bonding - Sharing of electrons. e.g, 2H atoms to form H molecule. Saturated: solution that contains the maximum concentration of solute at a specific temperature Supersaturation: occurs by heating/shaking, not used for drugs because they will precipitate the excess solute (resulting in an unstable solution) Entropy: randomness and disorder of molecules Entropy for a perfect crystal is at O at absolute zero temperature Kelvin Difference between properties between of amorphous (no specific structure) Irregular, no shape, melting point has a range, Unsymmetrical, Glass/Plastic. versus crystalline (insoluble) Regular, Characteristic shape, melting point at specific temperatures, Symmetrical, Diamond, Table salts Key difference: amorphous has better dissolution and solubility Difference between intrinsic (vacancies inside lattice) versus extrinsic Crystallinity defects (foreign atom enters into lattice) Intrinsic examples: Schottky defect:(oppositely charged atoms - vacant space in the lattice) vs Frenkel defect: ion leaving its original position to an interstitial position (but still within the crystal) Extrinsic: Foreign atom is inserted into lattice. Vacancy: Defect in crystal structure due to atom missing from lattice site. Polymorphism affects the physical/chemical properties (variation in the solubility, variation in the dissolution and melting point). At any temp/Pr. only one form of pure drug is stable; Unstable form = Metastable. -> convert stable at differing rate Crystalline may have different shapes in the crystal e.g., polymorphism, hydrate and solvent Amorphous is unstable and can be converted to the crystalline form which is associated with the change in physical, chemical properties of the medication Hydrate is a crystal structure containing water molecules Solvate will be a crystal structure containing solvens. Hygroscopic is the ability to retain moisture from environment where glycerin is one of the most hygroscopic agents, DeLIQuescence (takes moisture from environment and is dissolved or formed into a LIQuid) Lyophilization removes water from solids and is used to dry thermaliable medication (lyophilization is a drying method and not a sterilization method) Understand the phase diagram At 100C and 0.6 kPa, water exists in the water vapor (gas) form. What is the composition in the triple point of the phase diagram of water? Triple point is the mixture of ice + water + vapour  Eutectic mixtures: a combination of two substances and they would form liquid when mixed Know the substances used to create eutectic mixtures: phenol, camphor, methanol, thymol, aspirin, phenyl salicylate Difference between inclusion compound (incorporated, but does not change the lattice structure, clathrate (inclusion complex, one molecule is trapped within another compound, change in lattice structure), clathrate hydrates inclusion compounds formed by guest molecule within a cage of solid state water (an example of this is ice) Clathrate: used to increase solubility of some medications For example: when making a mixture of with two drugs, the product produced between the ingredient and the drug in this case will be more soluble Different properties: particle size affects solubility which affects bioavailability Surface area and particle size of the powder affect dissolution and absorption Solubility is also related to the surface area; focus on different mixing methods, drying methods (e.g., dry oven for powders, milling for reducing particle size) Wet method: screen of mesh, fluid bed processing (used for coating) Dry method: used for medication decomposed by liquid e.g., roll compactor and slugging methods. Problems during manufacturing: capping (top of tablet separates caused by rough punches versus lamination (tablet separates into horizontal layers) Definition of different modified release forms and examples: delayed release (aspirin), extended release (bupropion XL), targeted release (cancer drugs e.g., gefitinib, erlotinib) Know the laws of thermodynamics: 0th law: if two bodies are thermal equilibrium with a third body then the two systems are equilibrium within each other Work = Force x Displacement 1st law: energy can be converted from one form to another but not created or destroyed ΔU(internal energy) = Q(heat) - W(work) EntHalpy(H): if there is a question related to heat the answer may be EntHalpy Gibbs free energy equation to determine if the reaction is spontaneous or not Change in G=H(enthaply)-T(Kelvin)S(entropy) If the Gibbs free energy is negative it is a spontaneous reaction Liquid/vapour curve used to get the boiling point, solid/liquid curve used to get the melting point Eutectic point is known as the triple point in the phase diagram with a mixture of camphor and thymol An example of a question could be about a prescription of atropine requiring you to determine the role of glycerin or propylene glycol: the answer would be to identify they are co-solvents to enhance solubility  Collodions is pyroxylin which is used for warts Liniments are made up of camphor/thymol preparations Definitions of aqueous and non-aqueous solutions Raoult’s law: mixture of pure A and pure B where a positive deviation means that the vapor pressure of the mixture is greater than that of normal condition whereas a negative deviation is less than the vapor pressure of the mixture Raolut law is for ideal solutions Know the 4 different colligative properties: boiling point, freezing point, osmotic pressure, vapor pressure Colligative properties depend on the number of solute molecules Henry’s law relates the pressure to the amount of gas dissolved in the solvent In a diluted solution it is linear and ideal Henry’s constant is K, which is relevant when there are low solute concentrations, whereas Raolut’s law is be applied to higher concentrations. Acidic drugs dissolve better in basic mediums (high pH) whereas basic drugs dissolve better in acidic mediums (low pH) PKa affects solubility because it is related to the dissociation of acid; (pKa = -logKa), know that a high Ka = stronger acid) Understand that salting in/salting out can affect the solubility Common ion effect: precipitation of the product (AgCl) leading to insolubility Adding a polar functional group (COOH, OH) increases solubility, adding a long hydrocarbon chain will decreases solubility A high dissolution rate means that the drug is soluble and will be absorbed which means the bioavailability was reached. The Noyes-Whitney Equation (does not consider surface area) is used to calculate dissolution rate. Dc/dt = DS/h* (Cs-C). (h: thickness of diffused layer) What is the driving force? It is the variation in the concentration at the interface and the bulk of the solution. USP dissolution apparatus: tablets and capsules are usually made through type 1 and 2 Type 1: basket Type 2: paddle Type 3: reciprocating cylinder (for targeted drugs) Type 4: flow-through cell (for poorly soluble drugs) Intrfacial reaction: drug is being solubilized from a high concentration to a lower concentration where the driving force is the concentration gradient Ficks law is associated with diffusion. J=D(c1-c2/h) Drug goes from high to low concentrations (passive diffusion) The thickness of the membrane affects the diffusion  Two types of diffusion: steady (always the same amount of particles would diffuse at a time) non- steady (number of particles will change because the concentration gradient changes) Nernst law equation: distribution between oil and water is according to the K value (distribution coefficient) Example: K oil/water= 5/3, product is more lipophilic Hydrophilic Lipophilic Balance (HLB) ranges up to 18. Wetting agents have an HLB of 7-9 Emulsifying agents could be water in oil thus surfactants with low HLB (3-6) should be used whereas agents that are oil in water (hydrophilic), surfactants with a (high HLB 8-18) should be used Detergents have HLB values of 13-16 Emulsion can be unstable due to temperatures changes Creaming is reversible by shaking Cracking means that the phases have separated and the emulsion is ruined (irreversible) Dry gum method (no water initially): acacia is the emulsifying agent + mix with oil first then add water Wet gum method: gum + water = viscous, then add oil Auxiliary method: hand homogenizer In situ soap: (surface active agent is done in its place) e.g., mixing vegetable oil (oleic acid) with lime water (CaOH2) Emulsions are unstable and turbid Microemulsions are stable and transparent, and can be applied orally or over the skin Nernst potential: potential directly on the surface of the solid particle in the medium Zeta potential is the potential on the shear plane which is the second layer Differences between flocculted (particles flock together to form loose aggregates with weak bonds, rapid sedimentation, large sedimentation volume, clear supernatant and easily redispersed) versus deflocculated (particles are separated,repulsion between particles, small sediment volume, supernatant is turbid, difficult to redisperse) Thixotropy (when shaken well the viscosity will decrease, good for injections) Rheopexy (when shaken the product thickens) Plastic flow (has to be shaken to a certain yield value for the product to start flowing) Pseudoplastic flow (like a ketchup bottle flows a little but when shaken it flows even better) Idntify reaction based on diagrams given (e.g., under oxidation, primary alcohosl form aldehydes and secondary alcohols form ketones Tertiary alcohols are not oxidized : Difference between the graphs for zero order (linear graph) and 1st order degradation (curved graph) Shelf life is the time it takes for 90% of the product to remain and 10% to decompose  MDI (+spacer) is used for children under 5, and needs to be shaken and primed DPI not suitable for younger children, DPI doesnt require propellant but can use lactose as carrier agent, does not need to be shaken and no priming Main barrier for skin diffusion is stratum corneum (cells are called corneocytes) What is the most important factor affecting drug diffusion? oil-in -water (partition coefficient) Factors affecting flux (movement of drug across skin): K partition coefficient, concentration gradient, thickness of the skin, and diffusion coefficient (e.g., higher h = decreased movement across skin) Different methods of sterilization, filtration membrane uses 0.22 mm Examples of which products need to be sterile compounded (e.g. eye drops, injections) Focus on definition of LAL (Limulus Ambecoyte Lysate) If gel forms, then a pyrogen may be present To remove pyrogens use double distillation or reverse osmosis Know that suspensions cannot be given intravenously Know definitions of intravenous admixture and principles of aseptic techniques Difference between central line and PICC line PICC lines use hypertonic solutions whereas peripheral lines use isotonic solutions Types of administration (focus on IV piggyback - example IV antibiotics) Cornea is the main barrier for ophthalmic drug administration Main layers of the eye Know ophthalmic products must be sterile, know types of preservatives, know pH of ophthalmic medications is between 6.6 - 7.8 Understand definitions of density displacement factors and different preparation methods Memorize examples of bases and examples used for suppositories Know the different types of controlled drug delivery systems (hydrophilic, inert plastic matrix and liposome) Liposome delivery system e.g. amphotericin B has less side effects Antibodies are used in targeted therapy by adding linkers to attach therapeutic agents to antibodies Memorize the type of antibodies of biologic drugs e.g., drugs ending in “omab” = murine antibody, “ximab” = chimeric monoclonal antibody, “zumab” = humanized antibody, “mumab” = human antibody Know particle sizes for pulmonary drug delivery systems (0.5-10 um)  Know definitions and that < 2mL are used for subcutaneous injections whereas 2-5 mL for intramuscular injections Iodine number determines the number of double or triple bonds Saponification number determines the acidity of the product by adding KOH Examples of solvents injected IM Know the storage conditions of latanoprost and products containing latanoprost (fridge 2- degrees Celcius) Wet granulation cannot be used for aspirin Memorize definitions: trituration (motar and pestle), levigation (adding a little bit of liquid to reduce particle size), pulverization Understand definitions: geometric dilution (method used when small potent substances are diluted in large amounts of powder), spatulation, trituration, sifting, and tumbling May appear on the exam as a calculation: know the HLB equation Methanol alcohol causes blindness Treat methanol alcohol toxicity with ethanol or fomepizil Know glycerine and propylene glycol are co-solvents Gas equation: PV = nRT - might have to convert Temperature from Celious to Kelvin (by adding 275 to the celsius temperature) Arrhenius equation: equation that relates the decomposition of the medication to the temperature Difference between hypertonic, hypotonic and isotonic solutions