Impact of process variables on the micromeritic and physicochemical properties of spray-dried microparticles – Part II. Physicochemical characterisation of spray-dried materials

Abstract

In this work we investigated the residual organic solvent content and physicochemical properties of spray dried chlorothiazide sodium (CTZNa) and potassium (CTZK) salts. The powders were characterised by thermal, X-ray diffraction, infrared and dynamic vapour sorption (DVS) analyses. Solvent levels were investigated by Karl-Fischer titration and gas chromatography.Spray drying from water, methanol (MeOH) and mixes of methanol and butyl acetate (BA) resulted in amorphous microparticles. The glass transition temperatures of CTZNa and CTZK were ~192 ˚C and ~159 ˚C respectively. These materials retained their amorphous nature when stored at 25 °C in dry conditions for at least 6 months with no chemical decomposition observed. DVS determined critical relative humidity of recrystallisation of CTZNa and CTZK to be 57% RH and 58% RH, respectively.Inlet temperature dependant oxidation of MeOH to formaldehyde was observed; the formaldehyde was seen to deposit within the amorphous matrix of spray dried product. Spray drying in the open blowing mode coupled with secondary drying resulted in a three-fold reduction in residual BA (below pharmacopoeial permitted daily exposure limit) compared to spray drying in the closed mode. Experiments showed recirculation of recovered drying gas increases the risk of deposition of residual solvents in the spray dried product.

Formation and Physicochemical Properties of Crystalline and Amorphous Salts with Different Stoichiometries Formed between Ciprofloxacin and Succinic Acid

“…The critical relative humidity was established as previously described. 31,32 Briefly, an isotherm was calculated from the complete sorption profile. The amount of sorbed water was expressed as a percentage of the dry mass.…”

Impact of Alternative Solid State Forms and Specific Surface Area of High-Dose, Hydrophilic Active Pharmaceutical Ingredients on Tabletability

“…The particle size distributions of chlorothiazide sodium and potassium hydrated forms (CTZNa DH, CTZK DH and CTZK MH) and anhydrous forms (CTZNa ANH and CTZK ANH) were brought as close as possible to the size of spray dried salts using a mortar and pestle at room temperature and ambient relative humidity (RH) (35 to 40% RH), monitored using Testo TM RH and temperature data logger. The chemical purity of the produced solid-state forms was assessed using a HPLC method, as previously described 8 .…”

“…The amorphous form of chlorothiazide is difficult to produce, is physically unstable and prone to fast recrystallisation 5,6 . In contrast, sodium and potassium salts readily form amorphous forms on spray drying from solution, these forms being characterised by high-glass transition temperatures (Tg) of 192 °C (CTZNa) and 159 °C (CTZK) 7,8 . In a recent study we reported on the impact of specific surface area (TBET) of nanocrystalline microparticles (NCMPs) of chlorothiazide, produced by spray drying on the tabletability performance of this poorly compactible API 6 .…”

Impact of process variables on the micromeritic and physicochemical properties of spray-dried porous microparticles, part I: introduction of a new morphology classification system

“…All spray drying conditions used for CTZNa and CTZK (Table 1) rendered the materials powder X-ray diffraction amorphous, which was confirmed using DSC analysis. [18] The spray dried particles showed different morphologies when spray drying conditions and solvent type were varied ( Figure 1). To facilitate the description of the different morphologies, a morphology classification system (MCS) ( Table 2) for spray dried compounds was developed.…”

“…Experimentally this was established to be 2% w/v of anhydrous CTZNa or CTZK in MeOH. The content of BA was such that it did not result in precipitation of the active pharmaceutical ingredient during processing (samples [12][13][14][15][16][17][18][19][20]. By increasing the feed concentration, the production yield was increased to 75-80%.…”