T 6079 Use of a Modified Sodium Bicarbonate

T 6079 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 QR Code Only CONTACT INFORMATION: mtodd@spipharma. com 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%. METHOD(S) Dissolution Characteristics: The dissolution profiles of the raw material and formulated finished forms were determined using a Varian VK 7000 dissolution apparatus. Dissolution testing was carried out using Apparatus II, 900 m. L of fasted state simulated gastric fluid (Fa. SSGF), 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. Fa. SSGF (Biorelevant Media) at p. H 1. 6 instead of the phosphate buffer system (p. H 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 100 mg 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 0. 4375” FFBE tooling to a total tablet weight of 300 mg. Tablet hardness was normalized at 10 k. P between all formulations to minimize the influence that disintegration time would have on the release profiles. Raw Material Ibuprofen (Shandong Xinhua) Avicel 200 (FMC) Lubricant (Mg. St or SSF) Effer-Soda (SPI Pharma) Mannogem EZ (SPI Pharma) % Tablet 33. 3 30. 0 1 -3% 0 -7 14. 35 -17. 9 mg/Tablet 100. 0 90. 0 3. 0 -9. 0 0 -21. 0 43. 1 -53. 6 Mannogem 2080 (SPI Pharma) 14. 35 -17. 9 43. 1 -53. 6 TOTAL 100. 0 300. 0 CONCLUSION(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%. 1. Effer-Soda was easily incorporated into the swallow tablets containing 100 mg of ibuprofen. Ibuprofen tablets manufactured with 7% Effer-Soda displayed an increased rate of dissolution in Fa. SSGF, along with an overall increase of at least three-fold compared to formulations without Effer-Soda. Formulations containing Effer-Soda displayed an increased rate of release and an overall greater percentage release in Fa. SSGF 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. 2. These data demonstrate that the inclusion of a basic p. H 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. RESULT(S) Effer-Soda (%) Lubricant 0 0 7 7 SSF (1%) SSF (3%) Mg. St (1%) Mg. St (3%) 5 Minute Release (%) 0. 2 0. 6 3. 3 6. 4 0. 3 0. 5 3. 5 5. 6 60 Minute Release (%) 4. 0 3. 4 20. 9 19. 6 6. 9 5. 1 20. 8 17. 7 3. The lubricant choice or lubricant percentage had little or no effect on dissolution performance in these evaluations. www. spipharma. com © SPI Pharma 2017 All trademarks are the property of SPI Pharma, Inc.