Advanced

Methods for measurement of solubility and dissolution rate of sparingly soluble drugs

Larsson, Jesper (2009)
Department of Chemical Engineering
Abstract (Swedish)
The drug discovery process has changed dramatically during the last decade. The development of technologies such as combinatorial chemistry has introduced methods to synthesize massive numbers of new diverse compounds. This, combined with High-Throughput Screening techniques HTS, makes it possible in vast numbers to examine the potency in vitro of new compounds. This kind of approach is highly successful in thediscovery of new structures with superb in vitro potency, but ignores issues of absorption and bioavailability.

The dissolution rate and the release rate of a drug are essential to know for drug characterization. Poor aqueous solubility is likely to give rise to increased formulation difficulties during clinical development. Thus... (More)
The drug discovery process has changed dramatically during the last decade. The development of technologies such as combinatorial chemistry has introduced methods to synthesize massive numbers of new diverse compounds. This, combined with High-Throughput Screening techniques HTS, makes it possible in vast numbers to examine the potency in vitro of new compounds. This kind of approach is highly successful in thediscovery of new structures with superb in vitro potency, but ignores issues of absorption and bioavailability.

The dissolution rate and the release rate of a drug are essential to know for drug characterization. Poor aqueous solubility is likely to give rise to increased formulation difficulties during clinical development. Thus it is of interest to accurately measure solubility of sparingly soluble compounds. In order to measure the dissolution an instrument called rotating disc is used. The big benefit with the rotating disc method is that it uses well defined dissolution process and easy to use equipment

The purpose of this paper is therefore to give a wide introduction to dissolution in the Pharmacopeial area and a make a pre-study of the rotating disc. The focus will be on determining crucial factors that might affect the method.

There is no substantial analysis performed on the Shear distributions for USP 25, the rotating disc. The similarities to USP Apparatus II (same vessel as the rotating disk but a paddle instead of the disk), suggests that uneven shear distributions might be present. Thus it is important to examine the flow conditions.

The concentration has been measured and turbulent conditions have been introduced and second measurements have been taken. There is a difference in the measurements in concentration but not big enough to have any significance. The disturbance could be the result of other factors such as human influence, the tablet or the probe and the measuring device. The concentration in the lower part of the container which gives a higher concentration than the standard run indicates that we have an uneven shear distribution. But the difference is also too small to rule out other factors.

One major factor that affects the results is the method used to take samples, the probe and the relative long sampling time. This sampling in a moving medium results in a measurement in a volume. This volume measurement reduces the difference in concentration variations measured, because an average of the measurement is used.

The conclusion is that there probably are uneven sheer distributions that lead to different concentrations in the vessel. It is very important to use the same sampling point and the same measuring device and sampling times if you want to accurately compare measurements of different compounds. (Less)
Please use this url to cite or link to this publication:
author
Larsson, Jesper
supervisor
organization
year
type
H2 - Master's Degree (Two Years)
subject
keywords
Rotating disc, dissolution, pharmacopeial method, intrinsic dissolution
language
English
id
2117470
date added to LUP
2011-08-29 10:08:54
date last changed
2011-08-29 10:10:17
@misc{2117470,
  abstract     = {The drug discovery process has changed dramatically during the last decade. The development of technologies such as combinatorial chemistry has introduced methods to synthesize massive numbers of new diverse compounds. This, combined with High-Throughput Screening techniques HTS, makes it possible in vast numbers to examine the potency in vitro of new compounds. This kind of approach is highly successful in thediscovery of new structures with superb in vitro potency, but ignores issues of absorption and bioavailability.

The dissolution rate and the release rate of a drug are essential to know for drug characterization. Poor aqueous solubility is likely to give rise to increased formulation difficulties during clinical development. Thus it is of interest to accurately measure solubility of sparingly soluble compounds. In order to measure the dissolution an instrument called rotating disc is used. The big benefit with the rotating disc method is that it uses well defined dissolution process and easy to use equipment

The purpose of this paper is therefore to give a wide introduction to dissolution in the Pharmacopeial area and a make a pre-study of the rotating disc. The focus will be on determining crucial factors that might affect the method.

There is no substantial analysis performed on the Shear distributions for USP 25, the rotating disc. The similarities to USP Apparatus II (same vessel as the rotating disk but a paddle instead of the disk), suggests that uneven shear distributions might be present. Thus it is important to examine the flow conditions.

The concentration has been measured and turbulent conditions have been introduced and second measurements have been taken. There is a difference in the measurements in concentration but not big enough to have any significance. The disturbance could be the result of other factors such as human influence, the tablet or the probe and the measuring device. The concentration in the lower part of the container which gives a higher concentration than the standard run indicates that we have an uneven shear distribution. But the difference is also too small to rule out other factors.

One major factor that affects the results is the method used to take samples, the probe and the relative long sampling time. This sampling in a moving medium results in a measurement in a volume. This volume measurement reduces the difference in concentration variations measured, because an average of the measurement is used. 

The conclusion is that there probably are uneven sheer distributions that lead to different concentrations in the vessel. It is very important to use the same sampling point and the same measuring device and sampling times if you want to accurately compare measurements of different compounds.},
  author       = {Larsson, Jesper},
  keyword      = {Rotating disc,dissolution,pharmacopeial method,intrinsic dissolution},
  language     = {eng},
  note         = {Student Paper},
  title        = {Methods for measurement of solubility and dissolution rate of sparingly soluble drugs},
  year         = {2009},
}