Impact of process variables on the micromeritic and physicochemical properties of spray-dried microparticles--Part II. Physicochemical characterisation of spray-dried materials.
OBJECTIVE
In this work we investigated the residual organic solvent content and physicochemical properties of spray-dried chlorothiazide sodium (CTZNa) and potassium (CTZK) salts.


METHODS
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.


RESULTS
Spray-drying from water, methanol (MeOH) and mixes of MeOH and butyl acetate (BA) resulted in amorphous microparticles. The glass transition temperatures of CTZNa and CTZK were ∼192 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 the critical relative humidity of recrystallisation of CTZNa and CTZK to be 57% RH and 58% RH, respectively. The 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.


CONCLUSIONS
Experiments showed that recirculation of recovered drying gas increases the risk of deposition of residual solvents in the spray-dried product.
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, College Green, Dublin, Ireland.
Krzysztof J
KJ
Paluch
Lidia
L
Tajber
Maria I
MI
Amaro
Owen I
OI
Corrigan
Anne Marie
AM
Healy
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002740:Chlorothiazide / Q000737:chemistry*; D002849:Chromatography, Gas; D004355:Drug Stability; D004356:Drug Storage; D009930:Organic Chemicals / Q000737:chemistry; D010084:Oxidation-Reduction; D011208:Powders; D012997:Solvents / Q000737:chemistry*; D013696:Temperature; D044366:Transition Temperature; D014961:X-Ray Diffraction
D009930:Organic Chemicals; D011208:Powders; D012997:Solvents; D002740:Chlorothiazide