BE Formulasi Paracetamol Effervescent Powder yg Mengandung NaBik (Alikal Dolor®) vs Tab Paracetamol

Summary

This presentation discusses a bioequivalence study of paracetamol formulations, focusing on a test formulation (Alikal Dolor) and a reference formulation (Panadol). The study involves a randomized, open-label, crossover design with healthy volunteers. The primary pharmacokinetic parameters measured include Cmax, AUC, and Tmax. The goal is to determine if the test formulation is therapeutically equivalent to the reference formulation by assessing absorption rates and drug release profiles. Key aspects include regulatory compliance, ethical approval, and analysis using HPLC UV methods. The study adheres to BPOM guidelines and international standards to ensure valid, reliable results.

Takeaways

• 😀 The study focuses on a bioequivalence test of paracetamol formulations: Ever powder (test) vs. conventional paracetamol tablet (reference).
• 😀 The study uses a randomized, open-label, balanced two-way crossover design with 18 healthy subjects to minimize variability.
• 😀 Ethical approval and informed consent are necessary for clinical studies involving human subjects and interventions, following established regulations.
• 😀 The key pharmacokinetic parameters measured include Cmax (maximum plasma concentration), AUC (area under the curve), and Tmax (time to reach Cmax).
• 😀 AUC and Cmax data are analyzed using ANOVA, while Tmax is tested using the Wilcoxon test.
• 😀 The study is designed to determine bioequivalence if the 90% confidence interval for the test/reference ratio falls between 80% and 125%.
• 😀 Dissolution testing was conducted in vitro to confirm that both formulations release the drug similarly across different pH levels of the gastrointestinal tract.
• 😀 Blood samples were collected at 19 time points after dosing for plasma analysis, with HPLC-UV used to quantify paracetamol concentrations.
• 😀 Urine sampling was not performed since plasma concentration is sufficient for assessing bioequivalence, as paracetamol is primarily metabolized in the liver.
• 😀 The study adhered to BPOM guidelines and international regulations to ensure the validity and reliability of the bioequivalence results.
• 😀 If a formulation shows significantly greater bioavailability than the comparator, reformulation and retesting for bioequivalence may be required.

Q & A

What is the main focus of the study discussed in the presentation?

The main focus of the study is the bioequivalence testing of two formulations of paracetamol: an ever powder formulation with sodium bicarbonate and a conventional tablet formulation.

Why is bioequivalence testing required for this study?

Bioequivalence testing is required because the study involves testing a new formulation (ever powder with sodium bicarbonate) against an existing reference product (conventional paracetamol tablet). This ensures that the new formulation has similar pharmacokinetic properties, such as absorption and bioavailability.

What is the design of the study used for bioequivalence testing?

The study design used is a randomized, open-label, balanced two-way crossover design, with healthy volunteers who receive both the test drug and the reference drug in a crossover manner, separated by a washout period to minimize carryover effects.

What parameters were measured in the bioequivalence study?

The key pharmacokinetic parameters measured were Cmax (maximum plasma concentration), AUC (area under the curve), and Tmax (time to reach Cmax), all of which help to assess the absorption and overall bioavailability of the drug.

What criteria must be met for bioequivalence between the test and reference drugs?

For bioequivalence to be concluded, the 90% confidence interval of the test/reference ratio for AUC and Cmax must fall within the range of 80% to 125%.

Why was fasting required for the study participants before testing?

Fasting was required to prevent any food intake from affecting the absorption and pharmacokinetics of the drug, ensuring accurate and consistent test results.

What was the reason for choosing paracetamol as the active ingredient for the study?

Paracetamol was chosen because its oral bioavailability is high, making it a suitable candidate for evaluating bioequivalence based on pharmacokinetic data. Additionally, it is commonly used for pain relief, which is relevant to the study's therapeutic goals.

Why was urine sampling not included in the study?

Urine sampling was not conducted because the primary focus was on measuring paracetamol concentrations in plasma, which is more sensitive and sufficient for assessing drug absorption. Paracetamol is primarily metabolized in the liver, and its excretion through urine is not significant for bioequivalence testing.

How were the blood samples processed for analysis?

Blood samples were collected from the subjects, processed by centrifugation to separate the plasma, and stored at temperatures below -20°C until they were analyzed using HPLC with UV detection to measure paracetamol concentrations.

What challenges might arise from variations in the drug formulations during the study?

Variations in drug formulations, such as the differences in the form of the test and reference products (ever powder vs. conventional tablet), can affect the dissolution, absorption rate, and onset of action of the drug, potentially impacting bioequivalence outcomes.