Title:  Soft gelatin capsules containing particulate material

United States Patent:  6,217,902

Assignee:  R. P. Scherer Company (Basking Ridge, NJ)

Filed:  September 15, 1997

Disclosed are suspensions suitable for encapsulation in gelatin capsules, comprising a solid phase consisting of solid particles having a mean diameter of at least about 149 .mu.m, and a liquid phase capable of suspending the solid phase, the suspension having a predetermined rheology at a temperature suitable for encapsulation into gelatin capsules.

SUMMARY OF THE INVENTION

Although conventional rotary die encapsulation apparatus can be used to prepare soft gelatin capsules containing suspensions of solid particulate materials of mean diameters less than 180 .mu.m, problems arise when the particles have diameters in excess of 180 .mu.m. The present invention provides a solution to the problems associated with encapsulating microbeads or particles in suspensions.

In yet another aspect, the present invention provides suspensions of solid or particulate active agents, e.g., pharmaceutical agents, suitable for encapsulation in gelatin capsule. The suspensions of pharmaceutical agents may be encapsulated in gelatin capsules for subsequent oral administration. The invention also provides capsules suitable for a variety of non-oral uses.

Accordingly, a broad embodiment of the invention encompasses suspensions of active agents, the suspensions comprising a solid phase and a liquid phase capable of suspending the solid phase for at least a period of time sufficient to allow encapsulation into a gelatin capsule. The solid phase may comprise particles or beads having a mean diameter of at least about 149 .mu.m. The solid phase may also comprise single or multi-component particles having mean diameters of at least about 149 .mu.m. The inventive suspensions are pumpable at temperatures suitable for encapsulation into gelatin capsules. These suspensions, i.e., gelatin capsule fill materials, can be pumped without sedimentation or separation and without clogging of the various parts in a rotary die apparatus.

The invention further encompasses gelatin capsules comprising a fill material where the fill material is a suspension comprising a liquid phase and a solid phase.

The invention also encompasses methods and apparatus for preparing such gelatin capsules. The apparatus comprises a rotary die encapsulation machine modified to allow a suspension or slurry to be encapsulated without clogging of the various ports, tubes, and injection wedges. The apparatus alternatively may comprise a flat die encapsulation machine or a suitable liquid fill 2 piece hardshell encapsulation machine.

The invention thus provides gelatin capsules having particles or beads that may be visible within the capsule and readily discernable from the liquid phase.

The inventive gelatin capsules are also more tamper resistant since such capsules that have been tampered with or adulterated may be more readily distinguished.

The invention further provides gelatin capsules capable of releasing active agents at various predetermined times. For example, the liquid phase may comprise at least one active agent dissolved in the liquid phase available for immediate release while the solid phase may comprise a single agent or a plurality of different active agents formulated to have release profiles different from each other and from the agents in the liquid phase. Thus, the solid phase may comprise at least two different types of particles or beads, each containing a different active product.

Claim 1 of 17 Claims

What is claimed is:

1. A suspension of an active agent suitable for encapsulation in soft gelatin capsules, comprising a solid phase consisting of beads containing said active agent and having a solid exterior and a mean diameter of from about 149 .mu.m to about 2500 .mu.m, and a liquid phase suspending the solid phase substantially uniformly at a predetermined temperature, the suspension being pumpable and suitable for encapsulation into said soft gelatin capsule at said predetermined temperature; and wherein said beads comprise a coating effective to prevent interaction of the active agent with the liquid phase or the soft gelatin capsule.

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