Physicochemical Properties of Spray Dried Drugs: Phenobarbitone and Hydroflumethiazide

Abstract

The potential of spray drying to produce high energy drug forms was investigated using phenobarbitone and hydroflumethiazide. Whereas commercial phenobarbitone is normally Form II, the product produced by spray drying had a large specific surface area (17m ²/g) and physical properties similar to Form III. The apparent solubility of this spray dried material was 25% greater than that of Form II. An amorphous product was obtained on spray drying phenobarbitone with 10% PVP. Spray dried hydroflumethiazide was amorphous and had an apparent solubility 1.61 times that of the crystalline form. Co-spray drying hydroflumethiazide with 10% PVP also produced an amorphous system. Differential scanning calorimetry suggested that the system contained both amorphous drug and an amorphous drug-PVP complex. The product had an apparent solubility 2.5 times that of the pure crystalline drug. Spray drying, either in the presence or absence of excipients, can result in the formation of high energy drug polymorphs or amorphous phases not normally obtained by conventional precipitation procedures.