Margot M.S. Naaijkens⁽¹⁾, A.A. van Sorge^(2)
(1)Rijnstate Hospital - ARNHEM. Netherlands
⁽²⁾Rijnstate Hospital Arnhem - ARNHEM. Netherlands

	[Pharmacology]	[Dermatology]

MATERIAL & METHODS

PREPARATION

Composition Ibuprofen 5% 100 gram

Ibuprofen                           5 gram
N-Methylglucamine                4.73 gram
Hydroxyethylcellulose    2 gram / 1.8 gram
Kathon CG®                         50 mg
HCl 
Purified water                 ad 100 gram

Composition flurbiprofen 5% 100 gram

Flurbiprofen                        5 gram
N-Methylglucamine                   4 gram
Hydroxyethylcellulose    2 gram / 1.8 gram
Kathon CG®                         50 mg
HCl
Purified water                  ad 100 gram

PREPARATION PROTOCOL

Weigh all components.
Dissolve meglumine (N-Methylglucamine) in approximately 80 grams of water.
Subsequently, dissolve the ibuprofen/ flurbiprofen in the solution with meglumine (warming).
Correct the pH to 6.8 with HCl (solution has to stay transparent).
Weigh Kathon CG® (safety protocol).
Add Kathon CG® to the solution.
Put the solution in a tarred mortar.
Add hydroxyethylcellulose while mixing firmly.
Mix thorough until a smooth hydrogel is formed.
Add purified water up to a 100 grams.

Explanatory note to the usage of meglumine (N-Methylglucamine) and Kathon CG®

• To obtain a clear, transparent hydrogel the ibuprofen/ flurbiprofen has to be dissolved. This can be obtained by using equimolar quantities of meglumine dissolved in a part of the required water followed by dissolved ibuprofen/ flurbiprofen in the meglumine-solution. The usage of equimolar quantities of NaOH for obtaining a 5%-solution of ibuprofen/ flurbiprofen is not possible in the case of flurbiprofen (see solubility of flurbiprofen).

• Kathon CG® is the preservative in the gel. Kathon CG® is used in cosmetics. 50 mg correspond with 7.5 ppm; this concentration gives a good preservation and minimal skin irritation (see product information of Kathon CG®). By using Kathon CG®, the pH is a critical parameter for the conservation; a pH of 8 or higher weakens the conservation qualities, reason to keep the pH as low as possible (about 7; flurbiprofen/ ibuprofen are dissolved at this pH) (see product information of Kathon CG® and results of pH-series). The temperature must be kept under 50ºC to preserve conservation qualities of Kathon CG®. There are special safety protocols operative while using Kathon CG® in the preparation of the hydrogel because of it´s corrosive nature(see product information of Kathon CG®).

 

pH-series

The solubility of ibuprofen/ flurbiprofen with equimolar quantities of meglumine is determent for different pHs. This is done to examine at which pH the components are dissolved (the lower pH the better for the conserving activity of Kathon CG®). The used pH-buffersolutions are made according to the study of Herzfeldt and Kümmel (1983) to the dissociation constants and solubility’s of NSAIDs.

Buffer solutions (Herzfeldt and Kümmel) ⁽⁶⁾

BUFFER A
HCL 1M         14.1 ml
Glycine        75  mg
NaCl          552  mg
Aqua       ad 150  ml

BUFFER B
Na₂HPO₄ . 2H₂O    3.075 g
KH₂PO₄          420     mg
NaCl             22.5   mg
Aqua      ad   150     ml

The different pHs are made by using different combinations of buffer A and B (pH-curve buffer solutions).

Fig 1

Fig 2

SOLUBILITY

• Ibuprofen with equimolar quantities of NaOH dissolves in water while heating (5% solution is obtainable). The pH of the solution is 7.8.

• With equimolar quantities of NaOH a 5% solution of flurbiprofen is obtainable while heating up to 50 ºC; cooling results in precipitation.

• The solubility of flurbiprofen(sodium) is qualitatively determined at two pH-values:

Table 3

	Flurbiprofen	Flurbiprofensodium
pH 6.8	10 mg in 6 ml (0.17%)	10 mg in 2 ml (0.5%)
pH 7.2	10 mg in 3 ml (0.33%)	10 mg in 2 ml (0.5%)

• With equimolar quantities of meglumine dissolved in water a 5% solution of ibuprofen or flurbiprofen is obtained while heating. After cooling a transparent solution remains. The pH of the ibuprofen/meglumine-solution is 7.8. The pH of the flurbiprofen/meglumine-solution is 7.7. The pH of both solutions is lowered to 6.8 using HCL.

• With equimolar quantities of trometamol dissolved in water a 5% solution of ibuprofen or flurbiprofen is obtainable while heating. But during cooling it becomes cloudy. The pH of this solution is 7.1. Lowering or raising the pH of the trometamol/flurbiprofen-solution does not deliver a transparant solution.

¹ Equimolar quantity (example):

M(NaOH)/M(ibuprofen)* x grams ibuprofen = x grams NaOH

LEGENDA MOLECULAR WEIGHT

Compound	Molecular weight
Ibuprofen	206,28
Flurbiprofen	244,3
NaOH	40,00
Meglumine	195,22
Trometamol	121,1

Discussion Board

Any Comment to this presentation?

[ABSTRACT] [INTRODUCTION] [MATERIAL & METHODS] [RESULTS] [IMAGES] [DISCUSSION] [CONCLUSIONS] [BIBLIOGRAPHY] [PRESENTATION FILE] [Discussion Board]

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	[Pharmacology]	[Dermatology]

Margot M.S. Naaijkens, A.A. van Sorge
Copyright © 1999-2000. All rights reserved.

Last update: 13/01/00