Question # 1
Imagine that you are presented with the following information on three tablet formulations.
Formulation A:
Ingredient % w/w
Caffeine 10.0
Foremost® 316 Fast Flo® 59.7
Avicel PH-102 29.8
Magnesium Stearate 0.5
Formulation B:
Ingredient % w/w
Caffeine 10.0
Methocel K4M 10.0
Foremost® 316 Fast Flo® 53.0
Avicel PH-102 26.5
Magnesium Stearate 0.5
Formulation C:
Excipient % w/w
Caffeine 10.0
Methocel K4M 30.0
Foremost 316 Fast Flo 39.7
Avicel PH-102 19.8
Magnesium Stearate 0.5
Caffeine (model drug) was sieved through a 125 µm mesh sieve prior to inclusion in the formulation. Excipients were blended and 250 mg (8 mm in diameter, flat, round) tablets were manufactured.
Tablets were tested for drug release in 900 mL water using USP II apparatus and under same experimental conditions. Results are shown in the figure 1 below.
Pleae refer fugure 1 in the attached word file.
Figure 1. Release of incorporated drug from three tablet formulations tested under conditions described.
Discuss the information about these three tablet formulations provided considering different aspects from, for instance, tableting process that would be used in their production to the relevance of the drug release data provided to potential patient therapy.
Question # 2
2. ADH does not only catalyse the oxidation of ethanol, it also acts on other alcohols. This is of particular importance for methanol as ADH catalyses the conversion of methanol into formaldehyde which can cause blindness and death. An antidote to methanol poisoning is ethanol which acts as an inhibitor to the oxidation of methanol, allowing the safe discharge of methanol from the body.
a) Which type of inhibitor is ethanol in this reaction? Provide a rationale for your answer.
b) What are the oxidation states of carbon in methanol and formaldehyde?
c) The ADH catalysed oxidation of methanol is mechanistically similar to that of ethanol, requiring NADH / NAD+ as cofactor. Derive the overall reaction equation from the half equations and determine the standard potential, E0, and the Gibbs free energy, ?G0. The reduction potentials for formaldehyde and NAD+ are -0.182 V and -0.315 V, respectively.
d) If a person has consumed 50 ml methanol (a lethal dose), calculate how much absolute (100%) ethanol this person would have to consume to reduce the reaction rate ?0 to 3% of the original value. The KM for the oxidation of methanol by ADH is 0.01 M and KI for ethanol as inhibitor for this reaction is 0.001 M, Assume that the total fluid volume in the person’s body is 38 litres. The densities of ethanol and methanol are 0.789 g/ml and 0.791 g/ml, respectively. Assume Michaelis Menten kinetics for the reaction. Explain your procedure in words.( provide the essay with minimum 500 words )
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