Oral pulsed dose drug delivery system

Abstract

A multiple pulsed dose drug delivery system for pharmaceutically active amphetamine salts, comprising an immediate-release component and an enteric delayed-release component wherein (1) the enteric release coating has a defined minimum thickness and / or (2) there is a protective layer between the pharmaceutically active amphetamine salt and the enteric release coating and / or (3) there is a protective layer over the enteric release coating. The product can be composed of either one of a number of beads in a dosage form, including either capsule, tablet, or sachet method for administering the beads.

Description

[0001]This invention pertains to a multiple dosage form delivery system comprising one or more amphetamine salts for administering the amphetamine salts to a recipient.BACKGROUND OF THE INVENTION[0002]Traditionally, drug delivery systems have focused on constant / sustained drug output with the objective of minimizing peaks and valleys of drug concentrations in the body to optimize drug efficacy and to reduce adverse effects. A reduced dosing frequency and improved patient compliance can also be expected for the controlled / sustained release drug delivery systems, compared to immediate release preparations. However, for certain drugs, sustained release delivery is not suitable and is affected by the following factors:[0003]First pass metabolism: Some drugs, such as β blockers, β-estradiol, and salicylamide, undergo extensive first pass metabolism and require fast drug input to saturate metabolizing enzymes in order to minimize pre-systemic metabolism. Thus, a constant / sustained oral me...

AI Technical Summary

Benefits of technology

"The present invention provides an oral multiple pulsed dose delivery system for amphetamine salts that can be administered successfully. The system includes a pharmaceutical composition with a combination of immediate release and enteric release portions of the active ingredients. The enteric release coating provides a delay or \"lag time\" for the release of the drug, allowing for a controlled and complete release of the drug at the desired location in the gastrointestinal tract. The thicker enteric coating also prevents premature leakage of the drug and provides a more desirable drug release profile for therapeutic activity. The invention provides a pulsed enteric release of amphetamine salts that can be administered orally and provide a controlled and complete release of the drug at the desired location in the gastrointestinal tract."

Problems solved by technology

First pass metabolism: Some drugs, such as β blockers, β-estradiol, and salicylamide, undergo extensive first pass metabolism and require fast drug input to saturate metabolizing enzymes in order to minimize pre-systemic metabolism. Thus, a constant / sustained oral method of delivery would result in reduced oral bioavailability.

Gastric irritation or drug instability in gastric fluid: For compounds with gastric irritation or chemical instability in gastric fluid, the use of a sustained release preparation may exacerbate gastric irritation and chemical instability in gastric fluid.

These same factors are also problematic in pulsed dose formulation development.

Additionally, drug layering or core making for multiple unit systems is a time-consuming and hard-to-optimize process.

Particularly challenging for formulation scientists has been overcoming two conflicting hurdles for pulsatile formulation development, i.e., lag time and rapid release.

Due to their pH-dependent attributes and the uncertainty of gastric retention time, in-vivo performance as well as inter- and intra-subject variability are major issues for using enteric coated systems as a time-controlled release of drugs.

However, in the majority of subjects, no measurable amounts of the drug were observed in the blood, possibly due to instability of the drug in the distal intestine.

One disadvantage of current treatment is that a tablet form is commonly used which many young children have difficulty in swallowing.

Another disadvantage of current treatments is that two separate doses are administered, one in the morning and one approximately 4-6 hours later, commonly away from home under other than parental supervision.

This current form of treatment, therefore, requires a second treatment which is time-consuming, inconvenient and may be problematic for those children having difficulties in swallowing table t formulations.

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