Rapid release tablet formulation of micronized danazol powder produced by spray-freezing into liquid (SFL)

Abstract

To prepare a rapid release tablet formulation containing SFL micronized powders by direct compression and to investigate the effects of SFL powder compositions and tabletting excipient compositions on drug release. Three SFL micronized powder formulations were studied including danazol/polyvinylpyrrolidone (PVP) K-15 (2:1), danazol/PVP K-15/poloxamer 407 (4:1:1), and danazol/PVP K-15/sodium lauryl sulfate (SLS) (4:1:1). The physicochemical properties of SFL micronized powders were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), surface area analysis, contact angle, and dissolution. Five tablet formulations containing SFL micronized powders were investigated. The excipients used in the study included microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, sodium starch glycolate, and low-substituted hydroxypropyl cellulose. Tablets containing SFL micronized powder were analyzed for hardness, disintegration, friability, and dissolution. XRD results indicated that danazol was amorphous regardless of excipient type used in the SFL micronized powder. The surface area of SFL danazol/PVP K-15 powder, 79.9 m 2 /g, exceeded that of danazol/PVP K-15/SLS (48.0 m 2 /g) and danazol/poloxamer 407 (30.0 m 2 /g). Each of these powders exhibited similar and significantly enhanced dissolution rates compared to the micronized crystalline danazol. A rapid release tablet formulation containing SFL danazol/PVP K-15/SLS (4:1:1) was developed. The dissolution rate of micronized crystalline danazol control from the tablet was slow; only 40% of danazol dissolved in 10 min. However, 94% dissolved in only 10 min from tablets containing SFL micronized danazol/PVP K-15/SLS powder. This rapid dissolution rate was similar to the value for the SFL danazol/PVP K-15/SLS powder prior to tableting. Amorphous SFL powders with high glass transition temperatures (T g ), were physically stable during the direct compression process, based on dissolution rates and DSC measurements. Direct compression tablet formulation of SFL amorphous micronized powder led to desirable mechanical properties and a very rapid release profile approaching that of the SFL powder before tableting. A high T g excipient was utilized to prevent crystallization of the danazol during the process.