Oral administration of two therapeutic actives in a single dosage form can be complex if the intention is to have one active absorbed into the body and the other active remain substantially unabsorbed. For example, one active may be relatively soluble in the mouth at one pH, and the other active may be relatively insoluble at the same pH. Moreover, the absorption kinetics of each therapeutic agent may be substantially different due to differing absorption of the charged and uncharged species. These factors represent some of the challenges in appropriately co-administering therapeutic agents.
Co-administration of therapeutic agents has many applications. Among such areas of treatment include treating individuals who suffer from pain or other medical condition. Such individuals may have a tendency to suffer from serious physical dependence on the therapeutic agent, resulting in potentially dangerous withdrawal effects when the therapeutic agent is not administered to the individual. In order to provide treatment to patients, it is known to provide a reduced level of a therapeutic agent, which provides an effect of treating the condition, but does not provide the “high” that may be provided by the therapeutic agent. The drug provided may be an agonist or a partial agonist, which may provide a reduction in pain or other symptom that the patient is experiencing. However, even though these therapeutic agents provide only a low level of euphoric effect, they are capable of being abused by the individuals parenterally. In such cases, it is desirable to provide a combination of the therapeutic agent with a second therapeutic agent, which may decrease the likelihood of diversion and abuse of the first drug. For example, it is known to provide a dosage of an antagonist in combination with the agonist or partial agonist. The narcotic antagonist binds to a receptor in the brain to block the receptor, thus reducing the effect of the agonist.
One such combination of narcotic agents has been marketed under the trade name Suboxone® as an orally ingestible tablet. However, such combinations in tablet form have the potential for abuse. In some instances, the patient who has been provided the drug may store the tablet in his mouth without swallowing the tablet, then later extract the agonist from the tablet and inject the drug into an individual's body. Although certain antagonists (such as highly water-soluble antagonists) may be used to help reduce the ability to separate the agonist, the potential for abuse still exists. Further, incorporation of an antagonist in combination with the pain-relieving agonist has been found to reduce side effects associated with administration of the agonist, such as constipation and other undesirable effects. It is desired to provide a dosage that cannot be easily removed from the mouth once it has been administered.
There is currently a need for an orally dissolvable film dosage form that provides the desired absorption levels of the agonist and antagonist, while providing an adhesive effect in the mouth, rendering it difficult to remove once placed in the mouth and achieving optimum absorption of the agonist while inhibiting absorption of the antagonist.