Co-processed microcrystalline cellulose and sugar alcohol as an excipient for tablet formulations

[0066]This example illustrates formation of a co-processed microcrystalline cellulose / sugar alcohol by two different processes. FIG. 1A shows Process 1, a cool, low pH process. It uses ambient temperature water and involves adding acid MCC wetcake to a mannitol solution to form a mixture of MCC and mannitol (“MMCC”), which is, optionally, neutralized with ammonia. The resulting slurry (“Cool Neutral MMCC”) is spray dried. FIG. 1B shows Process 2, a hot, neutral pH process. Acid MCC wetcake is added to 70° C. water and, if necessary, neutralized with ammonia. Then a 70° C. mannitol solution is added to the neutralized MCC slurry. The resulting slurry (“Hot Neutral MMCC”) is spray dried.

[0067]The compaction profiles of 90% MCC / 10% mannitol compositions produced by these processes are shown in FIG. 2. There is no significant difference in the compactability of the samples made by processes 1 and 2

[0068]This example illustrates evaluation of co-processed MCC / sugar alcohol samples prepared by Process 1 of Example 1. MCC (PH grade wetcake) and mannitol (USP / NF grade) were co-processed as described in Process 1 of Example 1. Samples were produced with batch solids content necessary to solubilize all of the mannitol in each batch (mannitol solubility in water, about 18% solids at 25° C., pH about 5.2). Six samples were produced and spray dried on a 2.44 M (8 ft) Bowen dryer using standard MCC operating conditions. Inlet temperature 198-232° C.; outlet temperature 82-118° C. Samples were produced with 25%, 50% and 75% mannitol at two pH levels of 3.7 (unneutralized) and 5.8 (neutralized with NH4OH to pH 8). The physical properties of the samples are summarized in Table 1.

TABLE 1MannitolLODa>200 mesh (75 μm)LBDbSample #(%)(%)(%)(g / ml)pH1-1252.770.393.71-2501.7100.473.51-3751.350.453.41-4251.880.415.71-5501.430.485.81-6751.130.476.1aLoss on Drying.bLoose Bulk Density

[0069]Five additional samples of co-processed MCC / mannitol were produced as described in Example 2. Samples were produced with 0, 5, 10, 15, & 20% mannitol at pH 6.0. The physical properties of the samples are summarized in Table 2.

TABLE 2MannitolLOD>200 mesh (75 μm)LBDSample #(%)(%)(%)(g / ml)pH2-103.0150.385.72-252.7180.356.12-3102.8210.376.12-4152.3240.386.12-5202.3210.406.1