The development of a modified dissolution method suitable for investigating powder mixtures

L. R. Shaw, W. J. Irwin, T. J. Grattan, B. R. Conway

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

A novel dissolution method was developed, suitable for powder mixtures, based on the USP basket apparatus. The baskets were modified such that the powder mixtures were retained within the baskets and not dispersed, a potential difficulty that may arise when using conventional USP basket and paddle apparatus. The advantages of this method were that the components of the mixtures were maintained in close proximity, maximizing any drug:excipient interaction and leading to more linear dissolution profiles. Two weakly acidic model drugs, ibuprofen and acetaminophen, and a selection of pharmaceutical excipients, including potential dissolution-enhancing alkalizing agents, were chosen for investigation. Dissolution profiles were obtained for simple physical mixtures. The f1 fit factor values, calculated using pure drug as the reference material, demonstrated a trend in line with expectations, with several dissolution enhancers apparent for both drugs. Also, the dissolution rates were linear over substantial parts of the profiles. For both drugs, a rank order comparison between the f1 fit factor and calculated dissolution rate, obtained from the linear section of the dissolution profile, demonstrated a correlation using a significance level of P=0.05. The method was proven to be suitable for discriminating between the effects of excipients on the dissolution of the model drugs. The method design produced dissolution profiles where the dissolution rate was linear for a substantial time, allowing determination of the dissolution rate without mathematical transformation of the data. This method may be suitable as a preliminary excipient-screening tool in the drug formulation development process.

LanguageEnglish
Pages1147-1153
Number of pages7
JournalDrug Development and Industrial Pharmacy
Volume28
Issue number9
Early online date10 Aug 2002
DOIs
Publication statusPublished - 17 Nov 2002
Externally publishedYes

Fingerprint

Powders
Excipients
Dissolution
Pharmaceutical Preparations
Drug Compounding
Ibuprofen
Acetaminophen
Drug Interactions
Drug interactions
Screening
Mathematical transformations

Cite this

@article{144ded5f855143ebac1daa34865a2850,
title = "The development of a modified dissolution method suitable for investigating powder mixtures",
abstract = "A novel dissolution method was developed, suitable for powder mixtures, based on the USP basket apparatus. The baskets were modified such that the powder mixtures were retained within the baskets and not dispersed, a potential difficulty that may arise when using conventional USP basket and paddle apparatus. The advantages of this method were that the components of the mixtures were maintained in close proximity, maximizing any drug:excipient interaction and leading to more linear dissolution profiles. Two weakly acidic model drugs, ibuprofen and acetaminophen, and a selection of pharmaceutical excipients, including potential dissolution-enhancing alkalizing agents, were chosen for investigation. Dissolution profiles were obtained for simple physical mixtures. The f1 fit factor values, calculated using pure drug as the reference material, demonstrated a trend in line with expectations, with several dissolution enhancers apparent for both drugs. Also, the dissolution rates were linear over substantial parts of the profiles. For both drugs, a rank order comparison between the f1 fit factor and calculated dissolution rate, obtained from the linear section of the dissolution profile, demonstrated a correlation using a significance level of P=0.05. The method was proven to be suitable for discriminating between the effects of excipients on the dissolution of the model drugs. The method design produced dissolution profiles where the dissolution rate was linear for a substantial time, allowing determination of the dissolution rate without mathematical transformation of the data. This method may be suitable as a preliminary excipient-screening tool in the drug formulation development process.",
keywords = "Acetaminophen, Dissolution, Excipient, Ibuprofen",
author = "Shaw, {L. R.} and Irwin, {W. J.} and Grattan, {T. J.} and Conway, {B. R.}",
year = "2002",
month = "11",
day = "17",
doi = "10.1081/DDC-120014581",
language = "English",
volume = "28",
pages = "1147--1153",
journal = "Drug Development and Industrial Pharmacy",
issn = "0363-9045",
publisher = "Informa Healthcare",
number = "9",

}

The development of a modified dissolution method suitable for investigating powder mixtures. / Shaw, L. R.; Irwin, W. J.; Grattan, T. J.; Conway, B. R.

In: Drug Development and Industrial Pharmacy, Vol. 28, No. 9, 17.11.2002, p. 1147-1153.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The development of a modified dissolution method suitable for investigating powder mixtures

AU - Shaw, L. R.

AU - Irwin, W. J.

AU - Grattan, T. J.

AU - Conway, B. R.

PY - 2002/11/17

Y1 - 2002/11/17

N2 - A novel dissolution method was developed, suitable for powder mixtures, based on the USP basket apparatus. The baskets were modified such that the powder mixtures were retained within the baskets and not dispersed, a potential difficulty that may arise when using conventional USP basket and paddle apparatus. The advantages of this method were that the components of the mixtures were maintained in close proximity, maximizing any drug:excipient interaction and leading to more linear dissolution profiles. Two weakly acidic model drugs, ibuprofen and acetaminophen, and a selection of pharmaceutical excipients, including potential dissolution-enhancing alkalizing agents, were chosen for investigation. Dissolution profiles were obtained for simple physical mixtures. The f1 fit factor values, calculated using pure drug as the reference material, demonstrated a trend in line with expectations, with several dissolution enhancers apparent for both drugs. Also, the dissolution rates were linear over substantial parts of the profiles. For both drugs, a rank order comparison between the f1 fit factor and calculated dissolution rate, obtained from the linear section of the dissolution profile, demonstrated a correlation using a significance level of P=0.05. The method was proven to be suitable for discriminating between the effects of excipients on the dissolution of the model drugs. The method design produced dissolution profiles where the dissolution rate was linear for a substantial time, allowing determination of the dissolution rate without mathematical transformation of the data. This method may be suitable as a preliminary excipient-screening tool in the drug formulation development process.

AB - A novel dissolution method was developed, suitable for powder mixtures, based on the USP basket apparatus. The baskets were modified such that the powder mixtures were retained within the baskets and not dispersed, a potential difficulty that may arise when using conventional USP basket and paddle apparatus. The advantages of this method were that the components of the mixtures were maintained in close proximity, maximizing any drug:excipient interaction and leading to more linear dissolution profiles. Two weakly acidic model drugs, ibuprofen and acetaminophen, and a selection of pharmaceutical excipients, including potential dissolution-enhancing alkalizing agents, were chosen for investigation. Dissolution profiles were obtained for simple physical mixtures. The f1 fit factor values, calculated using pure drug as the reference material, demonstrated a trend in line with expectations, with several dissolution enhancers apparent for both drugs. Also, the dissolution rates were linear over substantial parts of the profiles. For both drugs, a rank order comparison between the f1 fit factor and calculated dissolution rate, obtained from the linear section of the dissolution profile, demonstrated a correlation using a significance level of P=0.05. The method was proven to be suitable for discriminating between the effects of excipients on the dissolution of the model drugs. The method design produced dissolution profiles where the dissolution rate was linear for a substantial time, allowing determination of the dissolution rate without mathematical transformation of the data. This method may be suitable as a preliminary excipient-screening tool in the drug formulation development process.

KW - Acetaminophen

KW - Dissolution

KW - Excipient

KW - Ibuprofen

UR - http://www.scopus.com/inward/record.url?scp=0036410865&partnerID=8YFLogxK

U2 - 10.1081/DDC-120014581

DO - 10.1081/DDC-120014581

M3 - Article

VL - 28

SP - 1147

EP - 1153

JO - Drug Development and Industrial Pharmacy

T2 - Drug Development and Industrial Pharmacy

JF - Drug Development and Industrial Pharmacy

SN - 0363-9045

IS - 9

ER -