Let us apply these steps to the provided data.

Step-by-Step Calculation:

Total volume of dissolution media: 250 ml Formulation equivalent to: 10 mg of drug Sample withdrawn: 1 ml each time Sink condition maintained: 1 ml PBS each time Dilution Factor: 2 Withdrawal time points: 0.5, 1, 1.5, 2, and 4 hr

Concentrations (µg/ml):

• 0.5 hr: 0.929
• 1 hr: 0.936
• 1.5 hr: 0.968
• 2 hr: 0.989
• 4 hr: 0.147

Calculate the amount of drug in each 1 ml sample:

Adjusted concentrations (considering dilution factor):

• 0.5 hr: 0.929 / 2 = 0.4645 µg/ml
• 1 hr: 0.936 / 2 = 0.468 µg/ml
• 1.5 hr: 0.968 / 2 = 0.484 µg/ml
• 2 hr: 0.989 / 2 = 0.4945 µg/ml
• 4 hr: 0.147 / 2 = 0.0735 µg/ml

Convert these concentrations to amounts in mg (since 1 µg = 0.001 mg):

• 0.5 hr: 0.4645 µg = 0.0004645 mg
• 1 hr: 0.468 µg = 0.000468 mg
• 1.5 hr: 0.484 µg = 0.000484 mg
• 2 hr: 0.4945 µg = 0.0004945 mg
• 4 hr: 0.0735 µg = 0.0000735 mg

Calculate the cumulative amount of drug released (adjusting for fresh media replacement):

The calculation of cumulative drug release accounts for both the drug remaining in the media and the drug withdrawn at each time point. To simplify, assume each sample is immediately replaced by fresh media of the same volume (1 ml).

Cumulative amounts:

• At 0.5 hr: 0.0004645 mg
• At 1 hr: 0.0004645 + 0.000468 mg = 0.0009325 mg
• At 1.5 hr: 0.0009325 + 0.000484 mg = 0.0014165 mg
• At 2 hr: 0.0014165 + 0.0004945 mg = 0.001911 mg
• At 4 hr: 0.001911 + 0.0000735 mg=0.0019845 mg

Calculate the percentage cumulative drug release:

o The total drug in the formulation is 10 mg.

o Percentage release at each time point = (Cumulative amount released/Total amount in formulation) × 100

o Percentages:

• At 0.5 hr: (0.0004645/10) × 100 = 0.004645%
• At 1 hr: (0.0009325/10) × 100 = 0.009325%
• At 1.5 hr: (0.0014165/10) × 100 = 0.014165%
• At 2 hr: (0.001911/10) × 100 = 0.01911%
• At 4 hr: (0.0019845/10) × 100 = 0.019845%

These percentages reflect the cumulative drug release at each time point.