Orally Disintegrating Tablet Compositions Comprising Combinations of High and Low-Dose Drugs

Abstract

The present invention is directed to pharmaceutical compositions comprising a plurality of taste-masked high-dose / low-dose drug-containing microparticles, dosage forms comprising such pharmaceutical compositions (such as an orally disintegrating tablet), and methods of making the pharmaceutical compositions and dosage forms of the present invention. Dosage forms comprising the pharmaceutical compositions of the present invention are improved homogeneous blends of high-dose and low-dose drugs which provide for more convenient and palatable administration of drug combinations, for example for treating pain, hyperglycemia, cardiovascular disease, and allergies.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]The present application claims priority to U.S. Provisional Application Nos. 61 / 174,780 and 61 / 174,788, both filed May 1, 2009.BACKGROUND OF THE INVENTION[0002]Moderate to severe pain can be effectively treated with opioid analgesics such as hydrocodone. However since many opioids are habit forming, the risk of abuse can be moderated by combining the opioid with a non-opioid analgesic such as acetaminophen, aspirin, ibuprofen, etc., thereby allowing effective pain management at lower doses of the opioid analgesic. Other medical conditions such as diabetes (hyperglycemia), cardiovascular disease, and schizophrenia are also effectively treated with drug combinations. However, the need to administer multiple dosage forms can result in problems such as patient compliance issues or dosage administration errors.[0003]One approach to preventing such problems is to combine multiple drugs into a single dosage form in order to minimize the number o...

AI Technical Summary

Problems solved by technology

However, the need to administer multiple dosage forms can result in problems such as patient compliance issues or dosage administration errors.

However, it is very difficult to reproducibly prepare homogeneous blends of hydrocodone and acetaminophen at the required 1:100 weight ratio (e.g., with a content uniformity having an RSD of 6% or less, as required by regulatory agencies worldwide).

However, such dosage forms have several disadvantages.

It is especially hard for the elderly or for children to swallow tablets or capsules, or to medicate patients who are unable or unwilling to swallow tablets or capsules.

Furthermore, conventional tablets or capsules usually must be administered with water, which is not always possible or convenient.

This leads to poor or even non-compliance with the treatment which consequently has a negative impact on the efficacy of the treatment.

However, the main drawback of taste-masking is slower dissolution of the drug(s) from effectively taste-masked microparticles.

Thus the very process of effectively taste-masking the drug-containing particles results in a substantially slower drug release, with concomitant slower systemic absorption of the drug in the gastrointestinal tract.

In some cases, slower drug release is a particular problem for ODT dosage forms which are intended to be bioequivalent to a reference listed immediate-release (IR) dosage form of the drug, for example bioequivalent to conventional tablet or effervescent tablet based IR dosage forms having a Tmax of less than an hour, and rapid-onset of action.

For ODT compositions containing combinations of two or more drugs (e.g., a high-dose / low-dose drug formulation) this problem is particularly acute, because the different drug components of the combination ODT may require different levels of taste-masking depending on the degree of bitterness of the drugs (i.e., drugs with low bitterness levels may require little or no taste-masking, while highly bitter drugs may require substantial taste-masking layers).

Achieving all of these properties is often quite difficult because thicker taste-masking layers may be required for adequate taste-masking of more soluble and / or more bitter drugs, which may make it difficult to obtain the required rapid drug release.

Thus, the preparation of clinically effective pharmaceutical compositions comprising at least a high-dose and a low-dose drug, particularly in the form of an ODT, is quite difficult and requires the balancing of many different and often competing requirements.

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