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Chapter: Pharmaceutical Drugs and Dosage: Colloidal dispersions

Pharmaceutical Drugs and Dosage: Colloidal dispersions - Review questions answers


Review questions

9.1 Which of the following statements about lyophilic colloidal disper-sions is TRUE?

A.      They tend to be more sensitive to the addition of electrolytes than lyophobic systems

B.      They tend to be more viscous than lyophobic systems

C.      They can be precipitated by prolonged dialysis

D.      They separate rapidly

E.       All of the above

F.       None of the above

9.2 Compounds that tend to accumulate at interface and reduce surface or interfacial tension are known as:

A.      Antifoaming agents

B.      Detergents

C.      Wetting agents

D.      Surfactants

E.       Interfacial agents

9.3 Indicate which of the following statements is TRUE and which is FALSE:

A.      Particle size of molecular dispersions is larger than a colloidal dispersion.

B.      Zeta potential influences colloidal stability.

C.      Nernst potential is higher than zeta potential.

D.      Zeta potential is electrothermodynamic in nature.

E.       Hydrophilic colloids form turbid solutions.

9.4 Classify disperse systems based on the particle size of their dispersed phase. Which of these systems are not visible to the naked eye?

9.5 A. List three mechanisms involved in acquisition of surface charge in a molecule.

B. Formulation of amino acids as solutions for parenteral adminis-tration requires careful consideration of the isoelectric point and the ionization status of the amino acids. Consider that your labo-ratory is given the amino acid alanine (structure given below) to be formulated into a solution.


i. Which chemical groups in alanine will affect its ionization.

ii. Assign either of the two pK values (2.35 and 9.69) of alanine to each group.

iii. Predict the structure of l-alanine at pH 2, 7, and 10.

9.6 A. What is zeta potential?

B. Zeta potential of the particles is routinely used for assessing the stability of pharmaceutical emulsions and suspensions. Suggest a reason why the surface charge of the particles is not used for this purpose?

9.7 Define and differentiate aggregation and coagulation in a colloidal system.

9.8 A. Define Stokes’ law.

B. Using the Stokes’ law equation, explain how we can minimize the sedimentation and creaming phenomena.

C. Sedimentation by ultracentrifugation is often utilized to deter-mine the particle size of submicron particles. Suggest the principle behind this application.

D. Suggest two reasons why this method is more suited to water-insol-uble compounds than to water-soluble molecules.

9.9 A lyophilic colloid can be:

A.      Hydrophilic

B.      Hydrophobic

C.      Lyophobic

D.      All of the above

E.       None of the above

Answers:

9.1 B. Most lyophilic colloids are polymeric molecules including gelatin and acacia; they spontaneously form colloidal solution, and tend to be viscous. Dispersion of lyophilic colloids is stable in the pres-ence of electrolytes.

9.2 D. Surfactants accumulate at the interface and lower the interfacial tension between oil and water phases.

9.3 A. False

B. True

C. False

D. False

E. False

9.4 Based on their particle size, colloidal systems are classified into molec-ular dispersions, colloidal dispersions, and coarse dispersions. Only coarse dispersions are visible to the naked eye.

9.5 A. Most substances acquire a surface electric charge when brought into contact with a polar medium, the possible charging mechanisms being ionization, ion adsorption, and ion dissolution.

·           Ionization: If the charge arises from ionization, the charge on the particles will be the function of pH and pKa. Proteins acquire their charge mainly through the ionization of carboxyl and amino groups to give COO− and NH3+ ions. Ionization depends strongly on pH of the medium. At low pH, a protein molecule will be positively charged, –NH2 NH3+, and at high pH it will be negatively charged, –COOH COO−. At a certain pH, specific for each individual protein, the total number of positive charges will be equal to the total number of negative charges, and the net charge will be zero. This pH is termed the isoelectric point of the protein.

·           Ion adsorption: A net surface charge can be acquired by the unequal adsorption of oppositely charged ions. Surfaces that are already charged have a tendency to adsorb counterions, which may reverse the surface charge.

·           Ion dissolution: Ionic substances can acquire a surface charge by virtue of unequal dissolution of the oppositely charged ions of which they are composed. For example, the particle of silver iodide in a solution with excess [I−] will carry a negative charge, but the charge will be positive if excess [Ag+] is present.

B. i. –COOH and NH2

ii. –COOH has 2.35 and NH2 has 9.69

iii. Low pH, NH3+; median pH 7, both groups ionized; basic pH, COO−

9.6 A. Zeta potential is defined as the difference in potential between the surface of the tightly bound layer of solvent/shear plane and the electroneutral region of the solution.

B. Electrophoretic properties are affected by the net charge on a particle, which includes that of an immobile solvent layer.

9.7 A. When the particles adhere by stronger forces, the phenomenon is called aggregation. Because of the large surface free energy of the dispersed-phase particles in emulsions, they tend to associate together by weak van der Waals forces forming light, fluffy con-glomerates. This phenomenon is called flocculation. Coagulation is the condition when the dispersed-phase particles merge with each other to form a single phase.

B. Coagulation is an irreversible process and leads to caking, whereas flocculation is the process of forming light fluffy conglomerates, which are reversible on shaking.

9.8 A. Stokes’ law defines the velocity of sedimentation as a function of the viscosity of the medium and the radius and the density of particles as per the following equation:

V = D2(ρ − ρ0)g / 18η′0

B. Creaming is the upward movement of dispersed droplets relative to the continuous phase, whereas sedimentation, the reverse pro-cess, is the downward movement of particles. These processes take place because of the density differences in the two phases and can be reversed by shaking. However, creaming is undesir-able because it provides the possibility of inaccurate dosing and increases the likelihood of some coalescence, which may take place owing to the close proximity of the globules in the cream.

Factors that influence the rate of creaming are similar to those involved in the sedimentation rate as indicated by Stokes’ law:

v= d2(ρs − ρ0)g / 18η0

where:

v is the velocity of creaming

d is the globule diameter

ρs and ρ0 are the densities of disperse phase and dispersion medium

ή0 is the viscosity of the dispersion medium (poise)

g is the acceleration of gravity (981 cm/s2)

C. According to Stokes’ equation, we can minimize the rate of creaming and sedimentation by (i) reducing the globule size, (ii) decreasing the density difference between the two phases, and (iii) increasing the viscosity of the continuous phase. This may be achieved by homogenizing the emulsion to reduce the globule size and increasing the viscosity of the continuous phase by the use of thickening agents such as tragacanth or methylcellulose for o/w emulsions and soft paraffin for w/o emulsions.

D. The rate of sedimentation is directly proportional to the diameter of particles if density/shape is the same.

E. Water-soluble compounds will dissolve while being processed, causing increase in viscosity of the medium and reduction in diameter. According to Stokes’ law, viscosity increase will affect the results.

9.9 D.

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