Browse Prior Art Database

Developing a discriminating Dissolution method for Elvitegravir

IP.com Disclosure Number: IPCOM000234713D
Publication Date: 2014-Jan-30
Document File: 4 page(s) / 183K

Publishing Venue

The IP.com Prior Art Database

Abstract

The classification of solubility according to USP of Elvitegravir is practically insoluble. The aqueous saturation solubility of Elvitegravir at pH 1.2, pH 4.5, and pH 6.8 is below 1µg/mL, therefore the addition of surfactants is needed for the dissolution method. To find a discriminating dissolution method, two different formulations with either a non-micronized or a micronized API were used. In conclusion, with the addition of 0.1 % of the surfactant SDS to the Dissolution media at pH 6.8 there was a significant difference in dissolution behaviour between the formulations of micronized (d90 = 2.3 µm) and unmicronized Elvitegravir (d90 = 56 µm).

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 55% of the total text.

Page 01 of 4

Developing a discriminating Dissolution method for Elvitegravir

Abstract

The classification of solubility according to USP of Elvitegravir is practically insoluble.

The aqueous saturation solubility of Elvitegravir at pH 1.2, pH 4.5, and pH 6.8 is below 1µg/mL, therefore the addition of surfactants is needed for the dissolution method.

To find a discriminating dissolution method, two different formulations with either a non- micronized or a micronized API were used.

In conclusion, with the addition of 0.1 % of the surfactant SDS to the Dissolution media at pH


6.8 there was a significant difference in dissolution behaviour between the formulations of micronized (d90 = 2.3 µm) and unmicronized Elvitegravir (d90 = 56 µm).

Introduction

It is commonly known that the use of micronized API´s ´may have an accelerating effect on the dissolution behaviour when formulating a given API. This fact is used in this case to find a discriminating dissolution method for Elvitegravir.

Sample

d(0.1)

d(0.5)

d(0.9)

[µm]

[µm]

[µm]

Elvitegravir - unmicronized


3.1

28

56

Elvitegravir - micronized


0.8


1.2


2.3

For this dissolution behaviour comparison, two wet granulation formulations were made with either a non-micronized (d90 = 56 µm) or a micronized API (d90 = 2.3 µm).

Experimental procedure and Methods

The following table shows the composition of wet granulation formulations of Elvitegravir, one with mannitol and one with MCC/lactose.

Table 1: Composition of the mannitol formulation with Elvitegravir

API / Excipient

[mg /

[% /

DF]

DF]

Elvitegravir

50,00 10,20

D-Mannitol

26,90 5,49

Aerosil

6,25 1,28

SDS

2,50 0,51

Crospovidone

6,25 1,28

HPMC 3

5,00 1,02

Water

-

Mannitol,,300 DC 145,35 29,66

MCC, 102

145,35 29,66

Croscarmellose Sodium 100,00 20,41 Mg stearate

2,40 0,49

The following table shows the MCC/lactose compositions of Elvitegravir wet granulation formulation.


Page 02 of 4

Table 2: Composition of the Cellulose formulation with Elvitegravir

API / Excipient

[mg / DF]

[% /

DF]

Elvitegravir

50,00 39,99

Lactose-mono, Granulac 200 3,65 2,92 MCC, Avicel 102

39,47 31,57

SDS

3,77 3,02

Ac-di-sol

11,24 8,99

HPC, Klucel EF

2,47 1,98

Water

-

MCC

10,00 8,00

Ac-di-sol

3,77 3,02

Mg-st

0,65 0,52

DISSOLUTION METHOD

Table 3: Parameters of the used dissolution method

Dissolution Parameters

sample:

Tablets with 50 mg Elvitegravir

apparatus:

Paddle (USP II)

medium:

900 ml NaH2PO4 pH 6.8 + 0,...