Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Patent
1995-05-17
1998-01-13
Azpuru, Carlos A.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
264 41, 42840221, A61K 9127, B01J 1302, B32B 516
Patent
active
057076480
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
This invention relates to compositions useful in the delivery of biologically active agents, and methods of making and using the same. More particularly, it relates to certain unique formulations advantageously formulated to enhance delivery of such biologically active agents as drugs, proteins, and polypeptides, including therapeutically-active ones used as medicaments, in capsules designed primarily for oral administration.
BACKGROUND OF THE INVENTION
There is a continuing need for new and improved delivery systems for biologically active materials. Many of the therapeutic agents emerging from the biotechnology revolution, as well as some older drugs such as insulin and calcitonin, consist of small and large molecule proteins. These drugs must now be injected into the patient because they are unable to survive the digestive process and do not readily pass through the mucosal lining of the gastrointestinal tract and enter the bloodstream. A new drug delivery system that would enable proteins to enter the bloodstream through, for example, the lining of the digestive system would be of great benefit.
Improved drug delivery systems could also provide much improved convenience for patients. For example, calcitonin is a generic peptide hormone used for treatment of osteoporosis and other diseases involving bone loss. Osteoporosis affects 24 million Americans, including 2/3 of the women past menopause. Currently, most calcitonin is delivered by injection. Calcitonin treatment for osteoporosis requires long-term administration with low but frequent doses of the drug. An oral or suppository formulation of calcitonin would offer great advantages to patients undergoing such treatments.
Recently, thermodynamically stable compositions, such as microemulsions, micelies, and liposomes, have been used in an attempt to formulate oral drug delivery systems for proteinaceous materials. Microemulsions are known in the art as thermodynamically stable compositions of an oil, surfactant, and aqueous component which when admixed form a stable, transparent solution having a particle size of below about 200 nm and generally greater than about 5-10 nm. The microemulsions are stable in that they do not break upon standing into normal emulsions, as do emulsions made to have particle sizes below about 200 nm by the use of high shear mixing devices. Microemulsions are further described by Science, Kahlweit, 248, 617-621 (1988) and in Bhargava et al., Pharm. Tech., 46-53 (March 1987), both of which are incorporated herein in their entirety by reference.
Water-in-oil (w/o) microemulsions are those microemulsions in which the aqueous phase is the internal phase. The w/o microemulsions can be determined by such tests as dye solubility and conductivity analysis. The w/o microemulsions generally will not initially disperse a water soluble dye. The w/o microemulsions also have a low conductivity of electricity.
Micellar solutions are in some respects similar to microemulsions, however they generally have a smaller particle size. The surfactants molecules assemble through cooperative association in the water to form aggregates called micelies. These micelles can solubilize an oil component, but generally not to the extent of a microemulsion. The term "swollen micelles" is sometimes used to refer to micellar solutions containing an oil component.
The aim of such compositions is to solubilize the proteinaceous material in an aqeuous component and to provide for the storage of the proteinaceous material while maintaining the bioavailability of the material.
Various active agents, especially proteins and peptides, must be administered to the intestinal region for proper uptake of the agent by the body. The bioavailability of these drug agents is commonly decreased upon exposure of the drug to conditions in the stomach. Therefore, the drug delivery composition is generally administered in an enterically coated capsule. Problems arise in formulating a drug delivery composition that can maintain the bioavailability of the drug
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Azpuru Carlos A.
LDS Technologies, Inc.
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