Transoral dosage forms comprising sufentanil and naloxone

Abstract

The invention pertains to methods that include administering to a subject a transoral dosage form comprising a pharmaceutical carrier and sufentanil, and maintaining a mean pH ranging from about 3.5 to about 5.5 during a dosing period after administration of the transoral dosage form as determined using an in vitro donor media test. Related dosage forms are also disclosed. Also disclosed are transoral dosage forms and related methods, wherein a transoral dosage form may comprise: (1) about 5 to about 1000 micrograms of sufentanil; (2) about 50 micrograms to about 100 milligrams of naloxone; and (3) acidifying material in an amount sufficient to provide a mean pH ranging from about 3.5 to about 5.5 during a dosing period after administration of the transoral dosage form as determined using an in vitro donor media test; wherein the dosing period begins no earlier than about 1 minute after administration of the transoral dosage form, and ends no later than about 120 minutes after administration of the transoral dosage form.

Description

[0001]This application is a continuation application of U.S. application Ser. No. 12 / 449,292, filed Jul. 31, 2009, which is a 371 filing of PCT / US08 / 01711, filed Feb. 8, 2008, which claims priority to 60 / 904,585, filed Mar. 2, 2007, and to 60 / 900,661, filed Feb. 9, 2007, all of which applications are hereby incorporated herein by reference.FIELD OF THE INVENTION[0002]The invention relates to dosage forms and related methods for the treatment of breakthrough pain. More particularly, the invention relates to methods and dosage forms for transorally administering sufentanil for treatment of breakthrough pain. Further, the invention relates to transoral dosage forms and related methods wherein the transoral dosage form includes sufentanil, naloxone; and a pharmaceutical carrier.DESCRIPTION OF RELATED ART[0003]Millions of subjects suffer from chronic pain each year. Chronic pain includes persistent pain, which occurs more or less continuously, and breakthrough pain (“BTP”), which is tran...

AI Technical Summary

Benefits of technology

The present invention provides methods and dosage forms that usefully combine sufentanil and naloxone. These methods and dosage forms have been found to be effective in treating breakthrough pain while also providing abuse deterrent features. Sufentanil offers several safety advantages over fentanyl, which is widely prescribed for BTP. Naloxone, an opioid antagonist, is an effective treatment for opioid overdoses. The transoral route of administration is advantageous because it avoids first-pass metabolic effects and may provide faster absorption and distribution to the central nervous system than other routes. However, there are problems with the low solubility of sufentanil free base, which limits its bioavailability. The invention provides attempts to address this problem, such as fentanyl effervescent buccal tablets that enhance solubility and shift the equilibrium towards the free base form of the drug.

Problems solved by technology

In theory, absorption of both opioids and opioid antagonists is undesirable, because the antagonists would counteract the opioid, thus leading to reduced analgesia.

However, there are problems that have been recognized in the art with the use of transoral sufentanil.

However, sufentanil free base has a very low solubility in aqueous fluids, thus significantly limiting sufentanil in solution that can permeate across oral mucosal tissues.

This very low solubility results in low bioavailability of the free base.

However, such systems can create a problem when the inventive dosage form comprises both sufentanil and naloxone, and / or pharmaceutically acceptable salts of sufentanil or naloxone.

Therefore, including both sufentanil and naloxone in a system such as the Durfee system would presumably lead to a poorly effective system because both the opioid and its antagonist would be absorbed.

For instance, ionized naloxone would be expected to be poorly absorbed transorally, because ionized species tend not to be very effective at being passively transported across the oral membranes.

Ionized sufentanil conventionally would be expected to be poorly absorbed transorally, rendering the dosage form ineffective at treating BTP.

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