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Donor

K. D. Permeable membrane. C 0. Blood. Donor solution. h. C 1. C d. C r. C 2. Donor. Receiver. Where, dM = change in mass transferred dt in change of time t D = diffusion constant C 1 = concentration in donor compartment

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Donor

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  1. K D Permeable membrane C0 Blood Donor solution h C1 Cd Cr C2 Donor Receiver

  2. Where, dM = change in mass transferred dt in change of time t D = diffusion constant C1 = concentration in donor compartment C2 = concentration in receptor compartment S = surface area of membrane Since K = C1 = C2 Cd Cr Under sink conditions and rearranging all constants, Where, P = permeability constant 6. 1 Fick’s second law of diffusion

  3. Factors effecting diffusion • Donor Concentration • Surface area • Partition coefficient

  4. Donor Concentration How is the concentration expressed? • Molarity • Normality • Molality • Mole Fraction

  5. Molarity solution

  6. Normality

  7. Normality (Contd.)

  8. Molality

  9. Mole Fraction

  10. Sample problems 1. Molarity is defined as A. gram molecular weight of solute in 1L of solution B. gram equivalent weight of solute in 1L of solution C. saturated solution of solute in 1L of solution D. ml of solvent required to dissolve 100g of solute E. gm molecular weight of solute in 1000g of solution. • An aqueous solution of exsiccated ferrous sulfate was prepared by adding 41.50g of FeSO4 to enough water to make 1000ml of solution at 18oC. The density of the solution is 1.0375 and the molecular weight of FeSo4 is 151.90. 2. Calculate the molarity of FeSO4. 3. The Normality of the above solution is: • An aqueous solution of glycerin , 7.00% by weight is prepared. The solution is found to have a density of 1.0149gm/cm3 at 20 oC. the molecular weight of glycerin is 92.0473 and its density is 1.2609 g/cm2 at 20 oC. 4. The molality of the solution is 5. A non-electrolyte is a substance which A. Forms at least two ions when dissolved in water B. Forms more than two ions when dissolved in water C. Has the same molarity as water D. Does not form ions when dissolved • Dissolved 10.0g of KNO3 (MW 101) in 100 ml of water • Determine the mole fraction of KNO3 • The molarity of the solution is:

  11. Factors effecting diffusion • Donor Concentration • Surface area • Partition coefficient

  12. Partition coefficient • Most of the drugs are either weak acids or weak bases • Drug molecules are absorbed at the biological barriers such as intestinal mucosa (oral drug administration) and lung epithelium (inhalation drug deliver) mostly in their unionized form. • The partition coefficient of unionized drug molecules is higher than the ionized species

  13. Sample questions 1) What are the important conditions (assumptions) of Fick’s first law Note: assumptions are the conditions that don’t appear in the equation a) Steady state and the concentration in the receiver compartment is zero b) Steady state and the concentration in the donor compartment is zero c) Surface area is 1 cm2 and thickness of the skin is zero d) Diffusion coefficient is 10-5 and log partition coefficient is 1 e) None of the above 2) Increase in one of the following factors will decrease the flux of a drug across the skin a) Surface area b) Diffusion coefficient c) Thickness d) Partition coefficient e) Donor concentration 3) Compound X is a weak base (pKa = 7.8). If applied as a cream, which of the following conditions will best enhance its permeability across the skin: a) Solubility = 10 mg/ml, pH = 7.8 b) Solubility = 20 mg/ml, pH = 5.8 c) Solubility = 10 mg/ml, pH = 9.8 d) Solubility = 20 mg/ml, pH = 9.8 e) Solubility = 5 mg/ml, pH 7.4 4) It is clear from the course material that Flux (J) = (DKC)/h, where: D = Diffusion coefficient; K = Partition coefficient; C = Donor concentration; h = Skin thickness. Based on your understanding, DK/h is a) Activity coefficient b) Solubility parameter c) Permeability coefficient d) Diffusion constant e) Fick’s first law

  14. Factor other than the solution pH that influences ionization

  15. Strong electrolytes

  16. Solubility of drugs Polymorphism determines the solubility of solids in liquids Crystalline solids • Solids are arranged in fixed geometric patterns or lattices and have an orderly shape and arrangement. Solids are mostly incompressible. Crystalline solids show very sharp melting points. • Six crystal forms are possible, cubic (sodium chloride), tetragonal (urea), hexagonal (iodoform), rhombic (iodine), monoclinic (sucrose) and triclinic (boric acid). • In the crystal lattice, ions or atoms can be held together by Vanderwaals, hydrogen bonding or by covalent linkage

  17. Amorphous solids • Amorphous solids may be also termed as super cooled liquids in which molecules are arranged in a random manner as in liquid state. • Glass, Synthetic plastics are good examples • Amorphous substances have a higher aqueous solubility than the crystalline solids. As a consequence their absorption across cellular barriers my be higher • Crystalline Novobiocin acid is poorly absorbed while the amorphous form is readily absorbed • It is difficult to distinguish between crystalline and amorphous substances based on the physical appearance. Beexwax and paraffin might look amorphous, but they are crystalline. • Differential scanning calorimetry can distinguish them based on the melting points. Crystalline solids have definite melting points

  18. Polymorphism • Substances such as sulfur may exist in more than one crystalline form • Polymorphs have generally have different solubilities and melting points • Incase of slightly soluble drugs, low solubility of some polymorphs might effect their therapeutic activity eg. Chloramphenicol palmitate • Polymorphism is involved in suspension stability eg. Cortisone acetate exists in 5 polymorphic forms. However only 1 of those is stable in water. All the other unstable forms will be converted the stable form upon storage

  19. Example: Cocoa butter (theobroma oil) • Cocoa butter exists in 4 polymorphic forms • The unstable gamma forms melts at 18 oC • Alpha form melts at 22 oC • Beta prime form melts at 28 oC • The most stable beta form melts at 34.5 oC • If cocoa butter is heated beyond 35 oC, the beta form nuclei are completely destroyed and the resultant melt will not cool above 15 oC

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