# Granulometric Analysis After Spontaneous Disintegration of Tablets Containing Micronized Purified Flavonoid Fraction (SIZE Study)

## TL;DR

This study compares how different manufacturers micronize a drug used for venous insufficiency, showing that particle size affects absorption and effectiveness.

## Contribution

The study introduces a non-pharmacopoeial method to assess micronization consistency across MPFF tablets from different manufacturers.

## Key findings

- Significant differences in particle size distribution were observed, especially in the 1-5 µm range.
- The reference product had the highest percentage of fine particles, likely improving dissolution and absorption.
- Variations in micronization processes suggest a need for standardized regulations to ensure drug consistency.

## Abstract

Background: Micronized purified flavonoid fraction (MPFF), primarily composed of diosmin and hesperidin, is used to treat chronic venous insufficiency by improving venous function. Traditional diosmin suffers from low bioavailability due to poor solubility, but micronization enhances absorption by reducing particle size. This advancement boosts therapeutic effectiveness, crucial for relieving venous disorder symptoms. Nevertheless, inconsistencies in micronization across manufacturers can affect drug effectiveness, highlighting the need for standardized processes.

Objectives: This study, called the SIZE study, aims to evaluate the particle size distribution of MPFF tablets containing diosmin/hesperidin (900/100 mg) from four Brazilian pharmaceutical manufacturers.

Methods: The spontaneous disintegration method was used to simulate the dissolution process, and granulometric analysis was performed using optical microscopy and image analysis. Samples were collected at 5 and 15 minutes post-disintegration, and particle sizes were categorized into ranges. The spontaneous disintegration method used was not based on the pharmacopoeia, but rather on a study published in 2018.

Results: Statistically significant differences were found between the products, particularly in the 1-5 µm range, with the reference product (Product I) showing the highest percentage of fine particles. This finer granulometry likely contributes to faster dissolution and improved absorption.

Conclusions: The SIZE study highlights the importance of particle size in drug solubility and bioavailability, suggesting that differences in the micronization process affect therapeutic efficacy. The findings underscore the need for standardized regulations on micronization to ensure product consistency.