Biopharmaceutics Questions

Pharmacy Assignment: Biopharmaceutics Questions

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Question 1 Fluocinolone acetonide is a topical corticosteroid drug with anti-inflammatory properties. The release of fluocinolone acetonide from a patch with a cross-sectional area of 11.5 cm2 and a membrane thickness of 72 μm was investigated. The lag time of diffusion was calculated to be 8.45 min. The concentration of fluocinolone acetonide inside the patch is 4.5 x 10-5 g cm-3 .

(a) Calculate the permeability coefficient (in cm s-1) of fluocinolone acetonide from this patch (K = 2.43).

(b) Calculate the total amount of fluocinolone acetonide (in μg) released from the patch in 24 hrs.

(c) The release of a drug from a patch is often said to follow zero order kinetics. Do drug patches always follow zero order kinetics? Give a brief explanation of zero order kinetics and from what you know of diffusion processes, why it is generally observed in drug patches.

(d) What type of extended release dosage form most closely follows zero order kinetics? Provide a description of its operation and explain how its rate of release can be modified. Why is it desirable to have zero order kinetics for an extended release dosage form?

Question 2 In vivo drug dissolution is a widely used tool in drug pre-formulation and quality assurance procedures for solid oral dosage forms. Being able to obtain accurate in vivo in vitro correlations (IVIVCs) saves a considerable amount of time and money when developing/modifying solid oral dosage forms. What factors need to be considered when developing in vitro dissolution tests in order to obtain accurate in vivo in vitro correlations (IVIVCs)? 2

Question 3 Read through the paper by Wickham et al. “The Design, Operation, and Application of a Dynamic Gastric Model” (2012).

(a) Briefly describe the operation of the dynamic gastric model. Include in your answer a discussion of the factors that need to be considered in designing an accurate gastric model.

(b) In Figure 2 of the paper, what are the differences in the amount/rate of paracetamol released as a function of time for the “fasted” and “fed” tests? How do these differences arise?

Question 4 A 100 g propylene glycol cream is prepared using the following ingredients: Ingredient Amount Propylene glycol 15 g Cetostearyl alcohol 12 g Cetomacrogol 1,000 3 g White soft paraffin 10 g Liquid paraffin 10 g Chlorocresol 0.1 g Purified water, freshly boiled and cooled to 1000 g

(a) List the likely function of each of the ingredients in the formulation.

(b) Draw the molecular structures of the emulsifying ingredients.

(c) Describe how the emulsifiers in the formulation are able to stabilize the o/w emulsion that forms.

(d) What formulation factors are important to the viscosity of an o/w emulsion?

Question 5 A newly developed drug that has been approved for Phase I trials has been sent to you to formulate into a 5 mg oral dosage form. The drug is weakly basic (pKb = 5.3), has a solubility of 0.13 mg/mL, has an average particle size of 5.8 μm, decomposes in light, and is hygroscopic. It also decomposes significantly in the presence of magnesium stearate and lactose. Suggest a suitable formulation for this drug.

Question 6 Fenac (Alphapharm) is a NSAID consisting of enteric coated tablets of diclofenac sodium (25 mg). They contain the following excipients: lactose, calcium hydrogen phosphate, microcrystalline cellulose, 3 maize starch, sodium starch glycolate, magnesium stearate, anhydrous colloidal silica, methacrylic acid copolymer, triethyl citrate, talc, titanium dioxide and iron oxide yellow CI77492.

(a) Briefly describe the likely function of each of the excipients used in these tablets.

(b) Do you think it is likely that a granulation step was used in manufacturing these tablets? Briefly discuss the reason why a granulation step is often used in tablet manufacture.

(c) These tablets have an enteric coating. Why was an enteric coating used on these tablets? Draw the molecular structure of the excipient used to produce the enteric coating and how it functions once the tablet is swallowed by the patient.

(d) Lactose is often used in tablet formulations and is often processed to make it more suitable for use in direct compression tablet formulations. Briefly describe the physical properties of lactose and how it is physically modified in order to make it more suitable for use in direct compression tablet formulations.

(e) The following excipients are part of a tablet drug formulation: pregelatinised starch; magnesium stearate, sodium lauryl sulfate, and sodium starch gycolate. What would be the effect on tablet dissolution if:

(i) the concentration of pregelatinised starch used was increased by 2%;

(ii) the concentration of magnesium stearate used was increased by 2%;

(iii) the concentration of sodium lauryl sulfate used was increased by 2%; and

(iv) the concentration of sodium starch gycolate used was increased by 2%? In each instance, provide a brief explanation to support your answer.

Question 7 A 50 kg woman was given a single IV dose of an antibacterial drug at a dose level of 5.8 mg/kg. Blood samples were taken at various time intervals. The concentration of the drug (Cp) was determined in the plasma fraction of each blood sample and the following data were obtained. Time (hr) Cp (μg/mL) 0.25 8.21 0.50 7.87 1.00 7.23 3.00 5.15 6.00 3.09 12.0 1.11 18.0 0.40

(a) Determine the pharmacokinetic parameters Vd, k, and t1/2 for this drug.

(b) This drug is not active at concentration below 2.3 μg/mL. What is the duration of activity for this drug?

(c) How long would it take for: (i) 80.0%; and (ii) 99.0% of the drug to be eliminated?

(d) If the dose of the drug was doubled, what will be the increase in duration of drug activity?