Influence of crystal habit on trimethoprim suspension formulation.
OBJECTIVE
The role of crystal habit in influencing the physical stability and pharmacokinetics of trimethoprim suspensions was examined.


METHODS
Different habits for trimethoprim (TMP) were obtained by recrystallizing the commercial sample (PD) utilizing solvent-change precipitation method. Four distinct habits (microscopic observation) belonging to the same polymorphic state (DSC studies) were selected for studies. Preformulation and formulation studies were carried out on suspension dosage forms containing these crystals. The freshly prepared suspensions were also evaluated for their pharmacokinetic behaviour on healthy human volunteers using a cross over study.


RESULTS
Variation of crystallization conditions produces different habits of TMP. Among the different crystal habits exhibiting same polymorphic state, the most anisometric crystal showed best physical stability in terms of sedimentation volume and redispersibility. However, habit did not significantly affect the extent of TMP excreted in urine.


CONCLUSIONS
Modification of surface morphology without significantly altering the polymorphic state can be utilized for improving physical stability of TMP suspensions. However, the pharmacokinetic profile remains unaltered.
Tiwary
A K
AK
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India. tiwary@pbi.ernet.in
Panpalia
G M
GM
D000328:Adult; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D006801:Humans; D008297:Male; D014295:Trimethoprim / Q000737:chemistry* / Q000493:pharmacokinetics / Q000652:urine
D014295:Trimethoprim