Oral pharmaceutical dosage forms

Abstract

Controlled release oral dosage forms suitable for administration of methylphenidate are provided. Abuse-resistant controlled release oral dosage forms suitable for administration of methylphenidate are also provided. Methods of treating ADD and ADHD using the oral dosage forms are also provided.

Description

CROSS REFERENCE TO RELEVANT APPLICATIONS[0001]This application claims the priority entitlement and full benefit of U.S. Provisional Application Nos. 61 / 198,244, filed 3 Nov. 2008, and 61 / 201,015, filed 5 Dec. 2008, pursuant to 35 U.S.C. §119(e).FIELD OF THE INVENTION[0002]The invention relates to oral pharmaceutical dosage forms and the use thereof. More specifically, this invention relates to controlled release oral pharmaceutical dosage forms and their use to deliver methylphenidate.BACKGROUND[0003]Formulation of drugs for delivery, particularly oral delivery, poses certain challenges. One challenge is to produce an oral controlled-release dosage form that provides for a relatively steady dose of drug over the approximately eight hours during which the dosage form passes through the gastrointestinal tract. Sustained release is often achieved by providing the tablet with a coating that delays release, or by formulating the tablet in such a way that it disintegrates relatively slowl...

AI Technical Summary

Benefits of technology

[0024]It is an advantage of the present invention that the controlled release oral dosage forms provide enhanced delivery kinetics of methylphenidate. It is also an advantage of the present invention that the abuse-resistant controlled release oral dosage forms are able to provide enhanced safety features and / or abuse-resistance properties in addition to enhanced in vivo pharmacological performance as compared with prior dosage forms. It is a further advantage of the invention that the inventive dosage forms can be readily constructed and used to provide a wide range of safer and more efficacious pharmacological solutions to the medical field. These and other objects, aspects and advantages of the present invention will readily occur to the skilled person upon reading the instant disclosure and specification.

[0025]FIG. 1 depicts the chemical structure of the d- and l-threo isomers of methylphenidate.

[0026]FIG. 2 depicts a comparison of mean pharmacokinetic profiles of immediate release (“IR”) methylphenidate Ritalin SR and a generic sustained release methylphenidate.

[0027]FIG. 3 depicts a comparison of plasma concentrations achieved with the Ritalin LA, Metadate CD, Concerta and Ritalin SR products.

[0028]FIG. 4 show the PK profiles from a 3-way crossover study of IR methylphenidate TID and Concerta without food (fasted) and after high-fat breakfast (taken from Swanson et al. (2003) Arch Gen Psychiatry 60:46-63) and mean plasma methylphenidate concentrations compared to TID methylphenidate (taken from Concerta label).

[0029]FIG. 5 shows a direct comparison of pharmacokinetics of methylphenidate released from Concerta (tablet formulation) and Metadate CD (capsule formulation), and Ritalin LA

Problems solved by technology

Formulation of drugs for delivery, particularly oral delivery, poses certain challenges.

One challenge is to produce an oral controlled-release dosage form that provides for a relatively steady dose of drug over the approximately eight hours during which the dosage form passes through the gastrointestinal tract.

A tablet, however, once ingested, is subject to considerable mechanical and chemical stresses as it passes through the esophagus, stomach, duodenum, jejunum, ileum, large intestine and colon, thus providing a significant challenge in maintaining controlled release of the drug formulation.

Acids, enzymes and peristalsis can cause the tablet to break apart, resulting in exposure of the inside of the tablet and an increase in surface area of the tablet material.

This will tend to increase the delivery rate of the drug or otherwise adversely affect the controlled release properties of the dosage form.

Another challenge is to produce a dosage form, including an oral dosage form, that reduces the potential for drug abuse.

The abuse of stimulants has been a growing problem.

A common and particularly dangerous cocktail of drugs is produced when stimulants are mixed with antidepressants or over-the-counter cold medicines containing decongestants.

Anti-depressants may enhance the effects of a stimulant, and stimulants in combination with decongestants may cause blood pressure to become dangerously high or lead to irregular heart rhythms, which in extreme cases may be fatal.

Solid dosage forms are particularly susceptible to abuse.

Administration of various abused drugs in this way produces a sudden high dose of drug into the blood stream making the user euphoric.

Other characteristics may include aggressiveness, stealing, lying, truancy, setting fires, running away, explosiveness, cognitive and learning problems as well as poor social skills.

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