The role of solution calorimetry in investigating controlled-release processes from polymeric drug delivery systems.
In this paper we investigate the potential role of solution calorimetry measurements in aiding the formulation of swellable matrices containing a mixture of HPMC and NaCMC, an ionic cellulose derivate. These polymers show a synergistic effect in their ability to modulate drug delivery rates; a matrix containing a 1:1 mixture of NaCMC and HPMC exhibits a significantly slower drug release rate than either polymer shows alone. The exact cause of this synergism is not clear and it is not an easy effect to examine using conventional means (such as dissolution testing). Here, we used solution calorimetry to study the system holistically. By comparing the measured response of a physical blend with a theoretical one (obtained by summation of the power-time data for each material), it was possible to assess if there was/was not any interaction which may explain the synergism. Furthermore, since a thermodynamic quantity was returned it was possible to establish if the interaction was favourable or unfavourable and so to obtain useful information to understand and predict the dissolution behaviour of polymeric systems containing the same materials. An unfavourable interaction was noted between NaCMC and the model drug (Diltiazem HCl); no interaction was seen between HPMC and the drug; and a favourable interaction was recorded when both polymers were formulated with the drug. The trend was mirrored by the t90 (the time required for 90% drug release) values determined from dissolution testing; NaCMC 10.8h, HPMC 16.4h, NaCMC and HPMC 19.1h. The data suggest that solution calorimetry measurements can be used to aid the selection of polymeric excipients to design controlled-release drug delivery systems.
Conti
Stefania
S
The School of Pharmacy, University of London, London, UK.
Gaisford
Simon
S
Buckton
Graham
G
Maggi
Lauretta
L
Conte
Ubaldo
U
D002151:Calorimetry / Q000379:methods*; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage; D003692:Delayed-Action Preparations / Q000737:chemistry; D004110:Diltiazem / Q000008:administration & dosage; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D012996:Solutions; D013607:Tablets
D003692:Delayed-Action Preparations; D011108:Polymers; D012996:Solutions; D013607:Tablets; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D004110:Diltiazem; D002266:Carboxymethylcellulose Sodium