1. Use of a Modified Sodium Bicarbonate and Lubricant Choice to Improve the Dissolution Rate of Weakly Acidic Drugs
Michael S. Todd, Greg Simon, Stephen Weide, Brian D. Wilson
SPI Pharma
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PURPOSE
To determine the impact on dissolution rate and release percentage of a BCS Class II model drug, ibuprofen, from a swallow tablet formulation containing a surface-modified sodium bicarbonate powder (Effer-Soda®, SPI Pharma) in combination with two different lubricants at a level of 1% or 3%.
Conclusion(s)
Effer-Soda was easily incorporated into the swallow tablets containing 100mg of ibuprofen. Ibuprofen tablets manufactured with 7% Effer-Soda displayed an increased rate of dissolution in FaSSGF, along with an overall increase of at least three-fold compared to formulations without Effer-Soda.
These data demonstrate that the inclusion of a basic pH modifying agent (surface-modified sodium bicarbonate powder) is a feasible approach to potentially increase the rate of release and overall release of weakly acidic drugs in fasted conditions.
The lubricant choice or lubricant percentage had little or no effect on dissolution performance in these evaluations.
Method(s)
Dissolution Characteristics: The dissolution profiles of the raw material and formulated finished forms were determined using a Varian VK7000 dissolution apparatus. Dissolution testing was carried out using Apparatus II, 900mL of fasted state simulated gastric fluid (FaSSGF), at 37°C (± 0.5°C) and agitated at 50 rpm. Sampling occurred at 1, 5, 15, 30, and 60 minutes to establish a complete dissolution profile. FaSSGF (Biorelevant Media) at pH 1.6 instead of the phosphate buffer system (pH 7.2) as specified in the monograph was chosen to represent a worst-case, fasted-state stomach conditions. Ibuprofen assay was determined by reverse phase chromatography.
Formulated Tablets: Swallow tablet formulations containing 100mg of ibuprofen were manufactured containing either 0% or 7% Effer-Soda in conjunction with two different lubricants, magnesium stearate or sodium stearyl fumarate (Lubripharm®, SPI Pharma), at two different percentages (1% and 3%). Tablets were compressed using ” FFBE tooling to a total tablet weight of 300 mg. Tablet hardness was normalized at 10kP between all formulations to minimize the influence that disintegration time would have on the release profiles.
Result(s)
Eight different formulations were evaluated containing Effer-Soda at either 0% or 7% of the formula composition, and either magnesium stearate or sodium stearyl fumarate at levels of 1% or 3%.
Formulations containing Effer-Soda displayed an increased rate of release and an overall greater percentage release in FaSSGF compared to formulations without Effer-Soda. The overall release was improved by at least three-fold in those formulations containing Effer-Soda at a 7% level compared to formulations without Effer-soda. Any impact on release due to lubricant was minimal when compared to the effect of Effer-Soda. At five minutes, tablets manufactured with Effer-Soda had already surpassed the 60 minute results for those tablets manufactured without Effer-Soda.
Effer-Soda (%)
Lubricant
5 Minute Release (%)
60 Minute Release (%)
SSF (1%)
0.2
4.0
SSF (3%)
0.6
3.4 7
3.3
20.9
6.4
19.6
MgSt (1%)
0.3
6.9
MgSt (3%)
0.5
5.1
3.5
20.8
5.6
17.7
Raw Material
% Tablet
mg/Tablet
Ibuprofen (Shandong Xinhua)
33.3
100.0
Avicel 200 (FMC)
30.0
90.0
Lubricant (MgSt or SSF)
1-3%
Effer-Soda (SPI Pharma)
0-7
0-21.0
Mannogem EZ (SPI Pharma)
Mannogem 2080 (SPI Pharma)
TOTAL
300.0
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