Citric acid as a pH-modifying additive in an extended release pellet formulation containing a weakly basic drug.
BACKGROUND
An extended release pellet formulation (ACES(R)) of the weakly basic drug propiverine was developed with spheronized citric acid crystals as starter cores.


METHODS
Coated pellets, consisting of several layers of functional coatings, were manufactured by fluid bed coating. Different coating levels were examined with regard to their effect on drug release. Release profiles from the formulations with or without pH modifier and the free base as well as the hydrochloride salt of the active ingredient were compared.


RESULTS
The coated citric acid starter cores led to a controlled release of the drug and the pH modifier, resulting from modulation of the microenvironmental pH throughout the dissolution period of 17 hours. If microcrystalline cellulose pellets are used as starter cores drug release is strongly pH-dependent. Significant differences in the drug release profiles were observed between the formulations containing the free drug base and those with the hydrochloride salt as a result of an altered microenvironmental pH.


CONCLUSIONS
The presented extended release pellet formulation is able to maintain a low pH within the pellet core and thus a sufficiently high drug solubility. By maintaining a low pH inside the pellets, a controlled drug release can be achieved.
Ploen
Jan
J
Business and Product Development, APOGEPHA Arzneimittel GmbH, Dresden, Germany.
Andersch
Jens
J
Heschel
Michael
M
Leopold
Claudia S
CS
D001561:Benzilates / Q000008:administration & dosage* / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019343:Citric Acid / Q000737:chemistry*; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D010276:Parasympatholytics / Q000008:administration & dosage* / Q000737:chemistry; D012492:Salts; D012995:Solubility; D013997:Time Factors
D001561:Benzilates; D003692:Delayed-Action Preparations; D005079:Excipients; D010276:Parasympatholytics; D012492:Salts; D019343:Citric Acid; C015586:propiverine; D002482:Cellulose; C109691:microcrystalline cellulose