Modification of the Solid-State Nature of Sulfathiazole and Sulfathiazole Sodium by Spray Drying

Abstract

Abstract. Solid-state characterisation of a drug following pharmaceutical processing and upon storage is fundamental to successful dosage form development. The aim of the study was to investigate the effects of using different solvents, feed concentrations and spray drier configuration on the solid-state nature of the highly polymorphic model drug, sulfathiazole (ST) and its sodium salt (STNa). The drugs were spray-dried from ethanol, acetone and mixtures of these organic solvents with water. Additionally, STNa was spraydried from pure water. The physicochemical properties including the physical stability of the spray-dried powders were compared to the unprocessed materials. Spray drying of ST from either acetonic or ethanolic solutions with the spray drier operating in a closed cycle mode yielded crystalline powders. In contrast, the powders obtained from ethanolic solutions with the spray drier operating in an open cycle mode were amorphous. Amorphous ST crystallised to pure form I at ≤35 % relative humidity (RH) or to polymorphic mixtures at higher RH values. The usual crystal habit of form I is needle-like, but spherical particles of this polymorph were generated by spray drying. STNa solutions resulted in an amorphous material upon processing, regardless of the solvent and the spray drier configuration employed. Moisture induced crystallisation of amorphous STNa to a sesquihydrate, whilst crystallisation upon heating gave rise to a new anhydrous polymorph. This study indicated that control of processing and storage parameters can be exploited to produce drugs with a specific/desired solid-state nature.

Bulk, surface properties and water uptake mechanisms of salt/acid amorphous composite systems

“…Amorphous ST started to crystallise to polymorph I ∼30 min after the end of the spray drying process regardless of the temperature and RH of storage. In contrast, spray dried STNa remained amorphous when stored for over a year in desiccated conditions at 5 ± 1 • C. Nevertheless, amorphous STNa rapidly deliquesced at ambient conditions (18-22 • C and 40-80% RH) (Bianco et al, 2012). All ST:STNa spray dried composites presented a diffuse halo pattern, characteristic of XRD amorphous materials (Fig.…”

“…0.5% (w/v) feed solutions were prepared by dissolving the APIs (Table 1) in a mixture of ethanol and deionised water at a v/v ratio of 9:1, as previously described (Bianco et al, 2012). Spray drying of ST and ST-STNa systems was performed using the following parameters: gas flow of 40 mm (473 L/h); aspirator rate of 100% and feed flow rate of 30% (8 ml/min).…”

“…The inlet temperature for the mixtures was adapted to the amount of salt employed in the system ranging from 85 to 90 • C and reported in Table 1. The salt alone was instead spray dried with an inlet of 160 • C so as to produce a dry powder (Bianco et al, 2012). Samples were transferred to Amebis humidity devices (Amebis Ltd., Ireland) at <5% RH (Bianco et al, 2012) and stored in a cold room at 5 ± 1 • C immediately after spray drying.…”

“…conditions. Nevertheless, it deliquesced when exposed to ambient RH conditions (Bianco et al, 2012). Deliquescence together with adsorption, capillary condensation, hydrate formation and absorption, is one of the known mechanisms of solid-water interactions (Airaksinen et al, 2005;Hiatt et al, 2011).…”

Enhancement of solubility and dissolution of ibuprofen microparticle prepared by ultrasonic spray drying

“…Many researchers apply spray drying for microparticle preparation of the drug to obtain reduced size to a specific size ranges (1-5 μm) [6,5] and shapes [11,[16][17][18]. Pyo et al, Kim et al, and Puri et al were using spray drying to control the amorphous states of the drugs because this state are often desired in order to achieve fast dissolution rates and high bioavailability [15,19,[20][21][22][23]. Xu et al, Li et al, and Shen et al improved solubility and dissolution of IBU by spray drying technique with using various polymer [1,21,24].…”