Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers

Autor: Jouko Yliruusi, Sirpa Vuorinen, Jaan Aruväli, Peep Veski, Karin Kogermann, Maija Hakola, Jyrki Heinämäki, Anna Penkina, Kristian Semjonov, Timo Repo
Rok vydání: 2015
Předmět:
Zdroj: Drug Development and Industrial Pharmacy. 42:378-388
ISSN: 1520-5762
0363-9045
DOI: 10.3109/03639045.2015.1054400
Popis: Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.
Databáze: OpenAIRE