Lecture 2 & 3 CH 2 Slides PDF

Colligative Properties and Dosage Form (DF) Design Key Concepts 1. Most common DFs are solid or liquid formulations – Closely parallels the chemical properties of the drug (s) in solution – The choice of pharmaceutical agents (excipients) and their forms • Ensures that a desired drug delivery is a...

Colligative Properties and Dosage Form (DF) Design Key Concepts 1. Most common DFs are solid or liquid formulations – Closely parallels the chemical properties of the drug (s) in solution – The choice of pharmaceutical agents (excipients) and their forms • Ensures that a desired drug delivery is achieved • Results in an improved therapeutic effect 3 Colligative Properties and Dosage Form (DF) Design Key Concepts (cont’d) 2. DF requires a vehicle for the administration of medication 3. DF contains agents that are medicinally inactive, pharmaceutical excipients 4. Is a determining factor in drug efficacy 4 Pharmaceutical DFs and Drug Delivery Considerations • It is by natural design that most drugs can be delivered orally • Basic strategy in dosage form design 1. 2. Achieve the desired drug absorption pattern Controlled release of the drug from the dosage form at the site of absorption 5 Pharmaceutical DFs and Drug Delivery Considerations • Solid DFs – Can be immediate or controlled release – Controlled release • includes delayed and extendedrelease 6 Pharmaceutical Dosage Forms and Drug Delivery Considerations Immediaterelease dosage forms • Follows Fick’s law of Diffusion • Predicts the rate of drug release • Based on solubility of the drug • Particle size of the drug material Controlled release-designed - • Delayed-release to have a more • Extended-release specific drug delivery 7 Pharmaceutical DFs and Drug Delivery Considerations • First-pass hepatic metabolic effect – Drugs absorbed from GI tract – Picked up by hepatic portal vein – Sublingual dosage forms bypass GI tract, avoiding first-pass (ex. nitroglycerin) 8 This Photo by Unknown author is licensed under CC BY. Liquid DFs • Solution – Aqueous solution dosage forms are more versatile than solids but faces serious limitations. • Poor water solubility of drug • Poor chemical stability – Hydrolysis of organic acid derivatives • Sterility requirements • Compatibility with biological fluids Colligative Properties of Solutions • Vapor Pressures of Solutions – Vapor pressure of the system is influenced by the mole fraction of components. – Systems can be classified as ideal or nonideal – Liquid and vapor are in equilibrium – Higher the vapor pressure; the faster liquid evaporates This Photo by Unknown author is icensed under CC BY-SA. 10 Colligative Properties of Solutions • Vapor Pressure Lowering – Addition of a solute lowers the vapor pressure of the solvent – Can be calculated the using the molal concentration of the solute ΔP =the vapor pressure of the solution m =mole fraction of solute in solution P° = the vapor pressure of the pure solvent at standard conditions 11 Colligative Properties of Solutions • Boiling Point Elevation – Addition of a solute to a solvent results in a solution of higher boiling point than the pure solvent. – To calculate this, you need molal concentration of the solute and the ebullioscopic constant (boiling point elevation), Kb. This Photo by Unknown author is licensed under CC BY-SA. 12 Colligative Properties of Solutions Freezing Point Depression – – – Solid and liquid have equal vapor pressure Addition of a solute to a solvent results in a solution of lower freezing point than that of the pure solvent. To calculate, you need molal concentration of the solute and the cryoscopic constant, Kf per kilogram of solvent Non-electrolytes ΔTf =Kf m Electrolytes ΔTf =iKf m ΔTf = freezing pt. depression Kf = molal freezing pt. depression constant of the solvent (cryoscopic constant) m = molal conc. of the solute in solution i = van’t Hoff factor* *accounts for the number of ions generated by a molecule in solution 13 Colligative Properties of Solutions • Osmotic Pressure (p) – Calculation requires a membrane • allow the passage of the solvent • inhibits passage the solute – Free energy • of the solvent in solution is less than that free energy of the solvent in its pure form • Solvent moves from high free energy state of the pure solvent to the lower free energy state of solution. M=Molarity (moles/L) R =gas constant T = Temperature (kelvins) 14 Colligative Properties of Electrolytes – Can be obtained by modifying equations with the van’t Hoff factor (i). – Factor represent the number of ions generated per molecule. 15 0.9% NaCl solution is iso-osmotic with biological fluids, therefore pharmaceutically is isotonic A solution that is iso-osmotic with biological may not be isotonic Isotonicity relates to the physiological compatibility Hypotonic: solution with osmotic pressure < biological fluids Isotonic Solutions Hypertonic: solutions with osmotic pressure > biological fluids 17 Preparation of Isotonic Solutions Key Concept(s) – liquid drug delivery systems must be isotonic with body fluids. This Photo by Unknown author is licensed under CC BY-SA-NC. – Sodium chloride and dextrose most common agents to adjust product tonicity. 18 Preparation of Isotonic Solutions 1. Sodium Chloride Equivalent (E) Method – 0.9% NaCl solution is isotonic with body fluids. – Sodium chloride equivalent (E) is defined as the equivalent weight to NaCl from a unit weight of the drug. – Use Table 2-4 Preparation of Isotonic Solutions 2. The D1% Method – Same as the expression ΔTf – the freezing point depression caused by a drug when the solutions strength is 1% w/v. – Isotonic solution will exhibit a freezing point depression of 0.52oC. Ddrug = D1% ´ wt of _ drug ( g ) ´100 VRx *Rx = volume of formulation 20 Preparation of Isotonic Solutions The D1% Method (cont’d) – Can also be used to determine the volume of water needed to make an isotonic solution containing a given weight of drug. Vwater = D1% ´ wt of _ drug ( g ) ´100 0.52 21 Preparation of Isotonic Solutions 3. The Liso Method – Liso is defined as the value of iKf when the molar or molal concentration of a drug produced a freezing point depression of 0.52oC. (Kf = cryoscopic constant) 22