Solid carriers for improved delivery of active ingredients in pharmaceutical compositions

Abstract

The present invention provides solid pharmaceutical compositions for improved delivery of a wide variety of pharmaceutical active ingredients contained therein or separately administered. In one embodiment, the solid pharmaceutical composition includes a solid carrier, the solid carrier including a substrate and an encapsulation coat on the substrate. The encapsulation coat can include different combinations of pharmaceutical active ingredients, hydrophilic surfactant, lipophilic surfactants and triglycerides. In another embodiment, the solid pharmaceutical composition includes a solid carrier, the solid carrier being formed of different combinations of pharmaceutical active ingredients, hydrophilic surfactants, lipophilic surfactants and triglycerides. The compositions of the present invention can be used for improved delivery of hydrophilic or hydrophobic pharmaceutical active ingredients, such as drugs, nutritional agents, cosmeceuticals and diagnostic agents.

Description

[0001]This application is a continuation of U.S. patent application Ser. No. 11 / 196,805, filed Aug. 2, 2005, which is a continuation-in-part of U.S. patent application Ser. No. 10 / 428,341, filed on May 1, 2003, now issued as U.S. Pat. No. 6,923,988, which is a continuation of U.S. Ser. No. 09 / 800,593 filed on Mar. 6, 2001, now issued as U.S. Pat. No. 6,569,463, which is a divisional of U.S. Ser. No. 09 / 447,690, filed on Nov. 23, 1999, now issued as U.S. Pat. No. 6,248,363, each of which is incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention relates to pharmaceutical delivery systems for pharmaceutical active ingredients, such as drugs, nutritionals, cosmeceuticals, and diagnostic agents. In particular, the present invention provides compositions and dosage forms including solid carriers for improved delivery of pharmaceutical active ingredients.BACKGROUND OF THE INVENTION[0003]Hydrophobic active ingredients, such as progesterone, cyclosporin, itraconaz...

AI Technical Summary

Benefits of technology

The present invention provides solid pharmaceutical compositions that have active ingredients in a rapid dissolvable and more solubilized state, resulting in faster dissolution upon administration to a patient. These compositions have increased chemical stability of the active ingredient, improved absorption and bioavailability, and better protection of the upper gastrointestinal tract from untoward effects of the active ingredient. Additionally, these compositions can improve the palatability of or mask the taste of unpalatable pharmaceutical active ingredients. The solid pharmaceutical compositions include a solid carrier, which can include a substrate and an encapsulation coat on the substrate, with the encapsulation coat including at least one ionic or non-ionic hydrophilic surfactant, optionally a pharmaceutical active ingredient, a lipophilic component, or both. The solid pharmaceutical compositions can be used in various dosage forms and methods of use.

Problems solved by technology

Hydrophobic active ingredients, such as progesterone, cyclosporin, itraconazole and glyburide present delivery challenges due to their poor aqueous solubility and slow dissolution rate.

Micronization / nanonization presents processing and stability challenges, as well as dissolution limitations, since the micronized / nanosized drug still possesses a high degree of crystallinity.

Liquid formulations present drug precipitation and packaging challenges, due to solvent evaporation.

Moreover, non-solid formulations are more prone to chemical instability and capsule-shell incompatibility, leading to the possibility of leakage upon storage.

Although these compounds are readily soluble in the aqueous gastrointestinal environment, they are poorly absorbed, due to poor membrane permeability and / or enzymatic degradation.

However, these compositions fail to maintain effective levels and type of enhancers for bioacceptable absorption enhancement.

Most solid dosage forms of hydrophilic active ingredients exhibit poor or no absorption of the active.

Moreover, these non-solid formulations suffer from the disadvantages of chemical instability, leakage and capsule shell incompatibility as discussed above.

Further, the problems of leakage and other disadvantages of liquid formulations are not present in solid carrier formulations.

To date, however, such solid carrier formulations generally have been limited to a few specific drugs, due to difficulties in formulating appropriate drug / excipient compositions to effectively coat the active ingredient onto a carrier particle.

Conventional solid dosage forms of hydrophobic active ingredients, such as tablets, or multiparticulates in capsules, often exhibit slow and incomplete dissolution and subsequent absorption.

These formulations often show a high propensity for biovariability and food interactions of the active ingredient, resulting in restrictive compliance / labeling requirements.

Due to the slow dissolution and dependence on gastric emptying, solid dosage forms often delay the onset of some hydrophobic active ingredients.

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