A study of the mechanisms of milling-induced enhancement of solubility and dissolution rate of poorly soluble drugs
type: CreativeWork
description: Milling and co-milling are well known techniques that have potential to enhance the solubility and/or dissolution rate of poorly soluble drugs. There are broadly two aims for this project. The first was to develop an understanding of how individual and combination of techniques may be used to explore the impact of milling on particle characteristics (including phase changes, fractures and change in particle size) as a function of milling time/speed, for a range of single powder materials. Anhydrous (lactose, sucrose), monohydrate (lactose) and dihydrate (trehalose) excipients and a poorly soluble drug (ibuprofen), were chosen as model substrates. Each material was micronized by ball-milling (for various time durations and milling speeds) and then characterized by a range of techniques, specifically, SEM, DSC, TGA, THz and dielectric spectroscopy. The second aim of the project was to investigate the impact of milling and co-milling on the solubility and dissolution rate of ibuprofen after co-milling with a variety of excipients (polymer and surfactants). The principle findings of this programme of work can be summarized as follows: i) ball milling of lactose monohydrate produces nano-structured systems with a mixture of damaged crystals and amorphous phase, that can be characterised by dielectric relaxation spectroscopy (DRS), ii) THz spectroscopy provides estimates for residual crystallinity in lactose monohydrate that were much lower than the estimates from the thermal techniques. Such estimates of residual crystallinity are considered to be more reliable given the fact that the spectroscopic measurement characterizes the material in its native state, whereas thermal techniques require a heating process, which tend to induce de-vitrification and mutarotation of lactose. In case of anhydrous materials, while there was agreement between thermal and THz techniques at long milling times, it was shown that the THz technique was susceptible to moisture absorption and cry…
abstract: Milling and co-milling are well known techniques that have potential to enhance the solubility and/or dissolution rate of poorly soluble drugs. There are broadly two aims for this project. The first was to develop an understanding of how individual and combination of techniques may be used to explore the impact of milling on particle characteristics (including phase changes, fractures and change in particle size) as a function of milling time/speed, for a range of single powder materials. Anhydrous (lactose, sucrose), monohydrate (lactose) and dihydrate (trehalose) excipients and a poorly soluble drug (ibuprofen), were chosen as model substrates. Each material was micronized by ball-milling (for various time durations and milling speeds) and then characterized by a range of techniques, specifically, SEM, DSC, TGA, THz and dielectric spectroscopy. The second aim of the project was to investigate the impact of milling and co-milling on the solubility and dissolution rate of ibuprofen after co-milling with a variety of excipients (polymer and surfactants). The principle findings of this programme of work can be summarized as follows: i) ball milling of lactose monohydrate produces nano-structured systems with a mixture of damaged crystals and amorphous phase, that can be characterised by dielectric relaxation spectroscopy (DRS), ii) THz spectroscopy provides estimates for residual crystallinity in lactose monohydrate that were much lower than the estimates from the thermal techniques. Such estimates of residual crystallinity are considered to be more reliable given the fact that the spectroscopic measurement characterizes the material in its native state, whereas thermal techniques require a heating process, which tend to induce de-vitrification and mutarotation of lactose. In case of anhydrous materials, while there was agreement between thermal and THz techniques at long milling times, it was shown that the THz technique was susceptible to moisture absorption and cry…
author: Hussain, Amjad
keywords: solubility enhancement, milling, co-milling,amorphous
license: https://dora.dmu.ac.uk/bitstreams/f66fdd01-6c17-48d5-955e-c7a76f3015d2/download
date published: 2015-02
date modified: 2026-07-24T06:18:54Z
provider: De Montfort University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: De Montfort University