Preparation of sustained release hydrophilic matrices by melt granulation in a high-shear mixer.
OBJECTIVE
The objective of this work was to prepare theophylline sustained release matrix tablets based on the combination of hydroxypropyl methylcellulose (HPMC K4M and K100M) and different meltable binders by melt granulation in a high-shear mixer.


METHODS
Dissolution profiles of each formulation were compared to those of TheoDur 200 mg tablets and the mean dissolution time (MDT) and similarity factor (f2 factor) were calculated. The matrices swelling behavior was investigated by texture analysis.


RESULTS
The results obtained show that the type of excipient influenced the drug release rate. In particular, the dissolution rate was delayed when lipophilic binders were used and only formulations containing Gelucire 50/13 or PEG 6000 with HPMC K4M had a profile similar to the commercial formulation. The release mechanism of theophylline from the formulations was described by Peppas's equation showing a non-Fickian release mechanism. The investigation of matrices swelling behavior showed that the gel layer thickness increased continuously over the time period studied. Moreover, a correlation between gel layer thickness and strength with the percentage released was found.


CONCLUSIONS
These results suggest that melt granulation could be an easy and fast method to formulate sustained release tablets.
Ochoa
Lourdes
L
Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country (UPV-EHU), Paseo de la Universidad no. 7, Vitoria-Gasteiz, Spain.
Igartua
Manuela
M
Hernández
Rosa Maria
RM
Gascón
Alicia R
AR
Pedraz
José Luis
JL
D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000032:analysis / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D005782:Gels; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods*
D003692:Delayed-Action Preparations; D005782:Gels; D013608:Tablets, Enteric-Coated