Aim: To measure the partition coefficient values of sulphamidine and acetylsulphamidine present in water/octanol solution at different pH.
Abstract: After measuring the pH of the buffer solution, two lots of eight bottles were prepared. 5ml of drug and 5 ml of buffer solution were added to each bottle and shaken for 30 minutes. Absorbance was then of the solutions in the bottles was then determined.
Introduction: Partition coefficient gives a measure of how a substance distributes in two different phase at equilibrium. Partition coefficient is utile in estimating the distribution of the drug within the body. There are two types of drugs, hydrophobic and hydrophilic drugs. The hydrophobic drugs have high partition coefficient and are distributed in hydrophobic compartment. Hydrophilic drugs, on the other hand, distribute in hydrophilic compartments.
Method: In order to achieve the experiment’s objective, it was inevitable that several tests be done. These tests required an aqueous buffer as well as the solution of the two drugs, which were provided. The blank used in the in UV spectrophotometer this case was pure octanol.
Task 1 pH measurement of the buffer: Before starting the experiment, it was essential that the Brittan Robinson buffer solution having the pH range as well as the pH meter be checked to ascertain that they in proper working conditions. This was followed by the measuring the pH of the buffer sample.
Task 2 Measurement of Absorbance-1: Just like the Brittan Robinson buffer solution having the pH range and the pH meter, the UV spectrophotometer was checked to ensure that it was working properly and standard spectra, and wavelength selected after some consultation. With Pure octanol as the reference, the absorbance of sulphamidine and acetylsulphamidine was then measured. In a bid to limit chemical interferences, the cells were thoroughly washed before taking any second measurements.
Task 3 Preparation of mixture: Two lots of eight bottles were prepared, one lot for the sulphamide and the other acetylsulphamide, and to each bottle, 5ml of the drug was added. First lot of the bottles was subjected to shaking in the shakers for 30 minutes after adding the buffer and the same procedure repeated for the second lot.
Task 4 Measurement of absorbance-2: Absorbance of the octanol layer in the two lots of eight bottles was measured as was done in part 1. Observation was made to see whether the solution in the bottle was clear or cloudy. From a clear solution, 4ml was taken and its absorbance measured.
Discussion: From the experimental findings, summarized in the results and graphs below, it can be seen that the k value of sulphamidine and acetylsulphumidine decreased with an increase in ph. It is deducible that the partitioning of a compound is depends largely on its ionization state and pH. Absorption in systematic circulation occurs only for the drugs with sufficient lipid solubility. However, the pH of the body system frequently changes, hence it is often difficult to predict liquid solubility with log P for most, if not all, ionizable drugs.
Conclusion: From the results above, it follows, therefore, that the lipid solubility of both drugs decreases with an increase in pH.
MODEL ELIMINATION
Aim: To discuss pharmacokinetics parameters by “one compartment” pharmacokinetics model.
Abstract: With flow rate at 25ml/min, 1ml of 100mg/ml sodium salicylate was taken into the flask and absorbance measured for 30 minutes at a wavelength of 540nm. Flow rate was then adjusted to 40ml/min and 50ml/min and distribution volume and clearance measured from absorbance.
Introduction: Complex physiological body processes can be easily represented with the help of Pharmacokinetics models. For this purpose, that Pharmacokinetics models can either be one-compartment or two-compartment model. One-compartment model, which is the preferred model for this experiment, is used in testing the drug, which rapidly equilibrates in the body. This model only uses one volume term (Vt) which is the volume of distribution (Vd) while two-compartment model, is used for drugs that equilibrate slowly.
Method:
Step 1: A 250ml flask was used to set up an apparatus overleaf. The experiment required a flow rate of 25ml/min, which was determined through measuring water in a cylinder as a time.
Step 2: 1ml of the 100mg/ml sodium salicylate solution was added into to the flask and the clock started.
Step 3: 1ml of water was collected at a time interval of 0.5, 1, 2, 5, 10, 15, 25, and 30 minutes respectively.
Step 4: Using 500mg/ml of sodium salicylate, a calibration curve was plotter in the range 0 to 500µg/ml
Step 5: To perform an assay, 3ml of ferric nitrate was added to 1ml of the sodium salicylate and the bottle shaken. Absorbance was then determined at a wavelength of 540nm.
Step 6: Using flow rates of 30-40ml/min and45-50ml/min, steps 1 to 3 were repeated in different flasks. Afterwards, the volume of the flask up to the overflow was measured.
Discussion: These results indicate that the drug is more bioavailable at a flow rate between 20 ml/min and 30ml/min. An increase in flow rate results in an increase in the rate of clearance. For flow rates above 30ml/min up to about 40ml/min, the clearance of a drug tends to be higher hence low bioavailability. Changes in flow rate also affect the Vd.
Conclusion: The results above indicate that increase in flow rate causes a rise in the rate of clearance of a drug. Similarly, low flow rate promotes slow clearance of a drug. In a nutshell, flow rate directly affects the bioavailability of a drug.
