Sustained-release microencapsulated delivery system

Abstract

Disclosed is a process for producing sustained-release powders that is fast, efficient, and economical. The process involves melting a naturally derived oil with a melting point above 110° F. in specially designed mixer through either the work energy input of the mixer shaft itself, or a specially fitted plow type mixer equipped with a heating tank, cooling unit, jacket for hot water circulation, and heated lines with nozzles for atomizing the hot oil to be sprayed on. The entire manufacturing process can be completed in about 5-30 minutes, and results in small, sustained-release particles that are free flowing and solid at room temperature. The preferred oil is a hydrogenated soy oil with a melting point range of 145° F. to 160° F. which is applied at about a 1% level by weight in a high shear mixer. Also included are sustained-release compositions for therapeutic agents such as drugs, botanicals, biological agents, fungicides, and fertilizers.

Description

[0001] The present application is a continuation-in-part of U.S. Pat. No. 6,953,593, issuing on Oct. 11, 2005 and filed on Feb. 1, 2000, which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION [0002] The present invention relates to a sustained-release microencapsulated compositions that can be produced efficiently and result in a very high percentage of active substance at the composition core. BACKGROUND OF THE INVENTION [0003] The benefits of producing sustained-release formulations for drugs or other therapeutic agents is now widely recognized in the medical literature and is utilized in many commercial products. It is important to distinguish at the out-set between solid monolithic dosage forms such as tablets and powders, and particles that are loosely packed into capsules. A sustained-release powder is typically made up of microparticles that are microencapsulated using a manufacturing process that enables them to be ingested as, for example, a powder...

AI Technical Summary

Benefits of technology

[0033] As mentioned, the present invention relates to a process for manufacturing pharmaceutical formulations that result in sustained-release microencapsulated particles, as well as certain compositions per se. These microencapsulated particles release a therapeutic agent gradually in a consistent fashion over a prolonged period of time, and can be manufactured in a way to yield a high percentage of an active agent core at a very economical cost. The process consists of heating and mixing naturally derived oil having a very high melting point with a therapeutic agent or drug until the agent or drug is well coated, and then cooling to room temperature until hard. The resultant particles are small, free flowing, and exhibit release profiles that can be adjusted to extend from 6-24 hours, for example. Other fibers, sugars, or polymers can be added in layers as an outer coat after cooling to affect the release profile and the hydrophobic properties of the particles, or directly to the matrix to accelerate drug release by creating additional channels for diffusion during erosion while dissolving. Other substances such as minerals can be added to the cores to provide additional weight to the particles causing them to sink due to heaviness.

[0034] In accordance with the invention, there is provided a microsphere that is produced by mixing the therapeutic agent with a naturally derived oil with a melting point at least above 110° C., and preferably about 140° F., in a vertical or horizontal high intensity schear mixer until the particles of the core substance are thoroughly mixed with the oil, and then cooling the hot melt to produce fine particles that exhibit excellent sustained-release properties. Surprisingly, the entire process can be completed in about 20 minutes or less in a jacketed high intensity mixer to melt the oil and intimately mix it with the core agent. The ideal high temperature melting point oil for this process is a hydrogenated vegetable oil such as hydrogenated soy oil, cottonseed oil, or stearic acid. The melting point ranges are from 140° F. to 165° F. Such an oil with these specifications is Dritex S® in flake form or Sterotex HM® which is a spray chilled, powder. Both are available from AC Humko, Memphis Tenn. The melting point profile is more uniform if the spray chilled powder is used.

[0035] Alternatively, a non-hydrogenated vegetable oil such as fractionated palm oil can be used. Such oil is a refined vegetable oil of non lauric origin derived from palm fruit,

Problems solved by technology

Microencapsulated powders may behave differently when subjected to the high pressures required to form tablets, and may fracture in the process.

In this case, diffusion and solubility issues become significant for sustained-release profiles.

Evaporation of the solvents becomes an environmental concern, and in many states, it is illegal to release these emissions into the atmosphere.

Aqueous or water based polymers are limited mainly to ethyl cellulose and methacrylic acid esters such as poly methacrylate dispersions.

Subjecting drugs and other therapeutic agents to 60° C. temperatures for 2 hours or more is likely to result in a loss of potency or degradation of active principles, and is especially problematic for substances with low melting points.

For example, botanical extracts have many volatile compounds that can be destroyed if kept at high temperatures for long period