Ion Exchange Resin
Formulations containing weak acid ion exchange resins (IER) are frequently used for immediate release of pharmaceutical agents in a patient's stomach. However, release from weak acid resins is slowed and/or reduced at higher than normal stomach pH levels. High pH levels could occur if the patient is taking medications such as proton pump inhibitors (PPIs) or has a disease state that induces hypochlorhydria or achlorhydria. In either case, a weak acid formulation may not release the medicament at a rate or to an extent adequate to achieve the desired therapeutic effect.
Approximately 60 million prescriptions were written for PPIs in 2006. Additionally, in the U.S., another 10 million people were reported to have self medicated with PPIs in 2008. Furthermore, about one in three adults used antacids on a regular basis. Collectively, these statistics suggest that close to 100 million people in the U.S. could be taking a drug that could significantly interfere with the release profile of a weak acid IER formulation. The history of prior art dosage forms indicates that a serious need exists for a novel and useful solid oral dosage form that provides an unexpected advancement in the science of IER dosage forms. For example, prior art dosage forms lack the ability to provide the immediate release properties of weak acid IER formulations when administered to a patient with stomach pH environments at about 1.5 to 2.0 and above. Surprisingly and unexpectedly, weak acid resinates can be formulated to have immediate release characteristics at pH levels above about 1.5 to 2.0. The present invention creates a release enhancing weak acid resin drug formulation by adding a release enhancing agent to the formulation to increase the rate and extent of drug release from the formulation such that it meets an a priori definition of immediate release.
Surprisingly it has been found that by adding a release enhancing agent with a strong affinity for the ionic resin to a weak acid resin drug formulation, much more rapid and complete release of a resinated drug can be attained in abnormal gastric fluid than otherwise would occur without the presence of the release enhancing agent in abnormal human gastric fluid wherein the pH is much higher than normal due to the use of drugs such as PPI or the presence of disease states such as H. pylori or atrophic gastritis that can lead to hypochlorhydria and achlorhydria.
Thus, one can attain the rapid release properties of weak acid resinates while retaining the low sensitivity to pH change associated strong acid resins by adding a release enhancing agent to the weak acid drug formulation.