Delivery of oral drugs

Abstract

Disclosed is a system for delivery of a drug comprising a multiple unit dosing device comprising a housing and an actuator, said device containing multiple doses of multiparticulates comprising drug particles, said device upon actuation delivering a unit dose of said multiparticulates, said drug particles having a mean diameter of greater than 10 μm to about 1 mm such that an effective dose of said drug cannot be delivered into the lower lung of a human patient. Also disclosed are novel methods, devices and dosage forms for delivering a drug.

Description

FIELD OF THE INVENTION [0001] The present is directed to a delivery device and method for the oral administration of therapeutic agents in powder form for gastrointestinal deposition. BACKGROUND OF THE INVENTION [0002] The most prominent mode of delivery of therapeutic agents is by the oral route by means of solid dosage forms such as tablets and capsules. Oral administration of solid dosage forms is more convenient and accepted than other modes of administration, e.g. parenteral administration. However, the manufacture, dispensing and administration of solid dosage forms are not without associated problems and drawbacks. [0003] With the manufacture of solid dosage forms, in addition to the active agent, it is necessary to combine other ingredients in the formulations for various reasons, such as to enhance physical appearance, to provide necessary bulk for tableting or capsuling, to improve stability, to improve compressibility or to aid in disintegration after administration. Howe...

AI Technical Summary

Benefits of technology

[0019] It is a further object of the invention to provide a method and system for delivery of multiple doses of a therapeutic agent in multiparticulate form which minimizes the need for inert pharmaceutical excipients.

[0061] The present invention is also directed to mouthpieces and devices which drop the unit dose vertically onto the tongue with minimal or no horizontal velocity. This action directs the unit dose down to the tongue and minimizes movement of particles toward the back of the throat in order to minimize or avoid pulmonary deposition. In preferred embodiments, when the device is utilized as intended, greater than 80% of the unit dose is administered from the device in a downward direction from about 45 degrees to about 135 degrees based on a vertical baseline independent of the device. Preferably greater than 90% of the drug follows this direction.

Problems solved by technology

However, the manufacture, dispensing and administration of solid dosage forms are not without associated problems and drawbacks.

However, these added excipients have been shown to adversely influence the release, stability and bioavailability of the active ingredient.

The added excipients are a particular problem with drugs which require a high dose in order to provide a therapeutic effect, e.g., biphosphonate drugs.

The inclusion of the additional excipient can make the final tablet extremely large which could result in esophogeal damage due to the physical characteristics of the dosage form if it is not swallowed properly.

Esophogeal damage can also be caused by toxicity caused by the drug itself, if the tablet becomes lodged in the throat or has an increased transit time through the esophagus, due to its increased size.

Further, the tableting of certain drugs has many associated production problems.

In particular, many drugs, e.g., acetaminophen, have poor compressibility and cannot be directly compressed into solid dosage forms.

Consequently, such drugs must either be wet granulated or manufactured in a special grade in order to be tableted which increases manufacturing steps and production costs.

Even strict adherence to these practices still is not a guarantee that acceptable variation will occur.

With the high cost of industrial scale production and governmental approval of solid dosage forms, such formulations are often available in a limited number of strengths, which only meet the needs of the largest sectors of the population.

Unfortunately, this practice leaves many patients without acceptable means of treatment and physicians in a quandary with respect to individualizing dosages to meet the clinical needs of their patients.

The dispensing of oral solid dosage forms also makes the formulations susceptible to degradation and contamination due to repackaging, improper storage and manual handling.

There are also many patients who are unable or unwilling to take conventional orally administered dosage forms.

For some patients, the perception of unacceptable taste or mouth feel of a dose of medicine leads to a gag reflex action that makes swallowing difficult or impossible.

Other patients, e.g., pediatric and geriatric patients, find it difficult to ingest typical solid oral dosage forms, e.g., due to tablet size.

Other patients, particularly elderly patients, have conditions such as achlorhydria which hinders the successful use of oral solid dosage forms.

While liquid formulations are more easily administered to the problem patient, liquid / suspension formulations are not without their own significant problems and restrictions.

The liquid dose amount is not as easily controlled compared with tablet and capsule forms and many therapeutic agents are not sufficiently stable in solution / suspension form.

Indeed, most suspension type formulations are typically reconstituted by the pharmacist and then have a limited shelf life even under refrigerated conditions.

Another problem with liquid formulations which is not as much a factor with tablets and capsules is the taste of the active agent.

The taste of some therapeutic agents is so unacceptable that liquid formulations are not a viable option.

Further, solution / suspension type formulations are typically not acceptable where the active agent must be provided with a protective coating, e.g. a taste masking coating or an enteric coating to protect the active agent from the strongly acidic conditions of the stomach.

However, such formulations also have drawbacks such as decreased bioavailability of the drug due to improper administration by the patient.

For example, if a patient's breathing is not coordinated with the activation of the device, the active agent will not reach its intended site of action which will lead to a decrease in therapeutic benefit.

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