Binder composition and method for processing poorly compressible drugs into tablets of predetermined hardness and friability

Aqueous dispersions of a binder composition of PVP/VA copolymer (60:40 by wt.) and plasticizer were spray dried in a laboratory scale spray dryer. The resultant powders were collected in a plastic bag. The glass transition temperature for each composition was determined and compared to copolymer without plasticizer (control). The results are shown in Table 1 below.

The data in Table 1 demonstrates that the plasticizer reduced the Tg of the copolymer by at least 10° C., and up to 27° C.

Free flowing powders of a binder composition of PVP/VA (60:40) plasticized with added PEG 4000 (5 and 10% w/w) or triethyl citrate (TEC) (5 and 10% w/w), having a particle size of 30μ, and a poorly compressible drug (acetaminophen) were prepared at a wt. ratio of 75:25 drug:binder composition. Then 0.5% silica and 0.5% lubricant were added and the mixture was compressed at a compression force of (lbs) 3000, 5000 or 7000. The hardness and friability values of the resultant tablets are shown in Table 2 below.

The data in Table 2 demonstrates that the drug tablet plasticized with PEG or TEC had a hardness value of 13.9 to 26.1 kP, as compared to only 5 to 7.4 kP for the control. Also friability was reduced from 3-9% for control (copolymer without plasticizer) to only 0.27 to 0.64% with added plasticizer.

The properties of the binder compositions of the invention were determined and compared to the copolymer itself as a control. The test powders were prepared in laboratory apparatus (composition A) or in a production minor spray dryer (5′×5′) using a rotary wheel atomizer with and without an air broom device (composition B). These copolymers were used as controls, or admixed with plasticizer (composition C) and (composition D). Drying was carried out at an inlet temperature of 150° C., an outlet temperature of 80° C. and a feed temperature of 50° C. The results are given in Table 3 below.

The results in Table 3 show that the binder compositions C and D reduced the Tg of the control copolymers A or B by >20° C., decreased the particle size of the copolymer powders.

Typical formulations of binder composition and drug ready for direct compression into tablets are given in Table 4 below.

Table 5 below shows the hardness and friability properties of tablets obtained by direct compression of the formulations of Example 4 at various compression forces.

The results in Table 5 show that the binder compositions of the invention provide hard tablets with low friability, even with a high amount of drug (77%) present in the tablet.

Tablets can be prepared as above using hydroxypropyl cellulose, hydroxypropyl methyl cellulose and polyvinylpyrrolidone as the polymer component in the binder composition. Similar results are obtained.

Tablets can be prepared as above using the following as plasticizers: polyethylene glycol, triethyl citrate, acetylated fatty acid glycerides, castor oil, dibutyl phthalate, diethyl phthalate, dibutyl sebacate, glycerol, glycerol monostearate, glyceryl triacetate, polyoxyethylene/polyoxypropylene copolymers and propylene glycol. Similar results are obtained.

While the invention has been described with particular reference to certain embodiments thereof, it will be understood that changes and modifications may be made which are within the skill of the art. Accordingly, it is intended to be bound only by the following claims, in which: