PhD Scientific Days 2018

Budapest, April 19–20, 2018

Study on the dissolution improvement of a poorly water soluble model drug using wet milling technique

Aghrbi, Isameddin

Isameddin Aghrbi, Istvan Antal

Department of Pharmaceutics, Semmelweis University, Budapest

Language of the presentation

English

Text of the abstract

Introduction: Cilostazol (CLZ) is used for the treatment of intermittent claudication and it belongs to Biopharmaceutical Classification System(BCS) Class II based on poor solubility and high permeability. Particle size reduction has been a much smart approach that can be applied to micro and nano-specific formulation recently.
Aims: The main objective of the study was to improve the dissolution of poorly soluble drug Cilostazol through microsuspension formulation by optimizing the milling parameters (surfactants, milling speed and milling time). The particle size of CLZ crystal was measured before and after milling.
Methods: Comminution was achieved by a planetary ball milling instrument using 300 µm sized zirconium oxide pearls. Particle size distributions were measured by LD (Laser Diffraction) technique. The dried dispersions of the milled suspension CLZ, unmilled suspension CLZ and pure CLZ powder were characterized by in-vitro dissolution profile, differential scanning calorimetry (DSC) and FTIR (Fourier-Transfom Infrared Spectroscopy).
Results: The Volume weighted mean particle size D(4,3) of the milled suspension CLZ was significantly smaller than the unmilled suspension of CLZ. The dissolution profile studies showed significant increase in the dissolution rate and saturation solubilities of the milled CLZ in pH 1.2 acidic buffer correlated to the unmilled and pure CLZ powder. In contrast, the dissolution study in pH=6.8 phosphate buffer showed that there was no significant difference between the dissolution profiles. Solid state characterization studies (DSC and FTIR) showed partial crystalline-amorphous transition in the milled dried CLZ suspension.
Conclusions: Both the dissolution rate and water solubility of the cilostazol model drug was improved by wet milling technique using pearls.

Data of the presenter

Doctoral School 03: Pharmaceutical Sciences
Program: 01. Modern Trends in Pharmaceutical Scientific Research
Supervisor: Dr. Istvan Antal
E-mail address: antal.istvan@pharma.semmelweis-univ.hu