Dissolution enhancement of an insoluble drug by physical mixture with a superdisintegrant: optimization with a simplex lattice design.
The aim of the present work was to optimize a tablet formulation containing a physical mixture of a practically insoluble drug (prednisone) with a superdisintegrant (croscarmellose sodium) and two filler-binders characterized by differing water solubility (dicalcium phosphate dihydrate and anhydrous beta-lactose). Crushing strength, disintegration, and dissolution were measured for 10 formulations distributed over a factor space according to a simplex lattice design for a special cubic model. Multiple linear regression analysis was used to assess the best fit for each variable. The model predicted that increasing the amount of disintegrant to a critical amount (50%) would result in reduced disintegration time for dicalcium phosphate/beta-lactose ratios > 0.3, no changes in disintegration time for ratios < 0.3, and for all ratios an improvement in dissolution at 10 min. Crushing strength values of dicalcium phosphate increased with increasing disintegration concentration but not for beta-lactose tablets. The physical mixture of a practically insoluble drug with a superdisintegrant was confirmed as a valid approach to the improvement of dissolution, even in presence of other components. The solubility of the filler-binders influenced the minimum amount of disintegrant needed; when a soluble diluent was used, the amount of disintegrant required was reduced.
Ferrari
F
F
Department of Pharmaceutical Chemistry, University of Pavia, Italy.
Bertoni
M
M
Bonferoni
C M
CM
Rossi
S
S
Caramella
C
C
Bolhuis
G K
GK
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry*; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D006245:Hardness Tests; D007700:Kinetics; D007785:Lactose / Q000737:chemistry*; D011241:Prednisone / Q000008:administration & dosage / Q000737:chemistry*; D012044:Regression Analysis; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets
D000893:Anti-Inflammatory Agents; D002130:Calcium Phosphates; D005079:Excipients; D013229:Stearic Acids; D013607:Tablets; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C031183:stearic acid; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; D007785:Lactose; D002266:Carboxymethylcellulose Sodium; C485829:calcium phosphate, dibasic, anhydrous; D011241:Prednisone