Design, development and in-vitro evaluation of diclofenac taste-masked orodispersible tablet formulations.
BACKGROUND
Fast onset of action is prerequisite for acute pain medication. A palatable orodispersible medicine of diclofenac providing rapid analgesic effect should improve patient compliance and treatment.


OBJECTIVE
In the present study, diclofenac taste-masked orodispersible tablets (ODTs) with fast release characteristics were developed. Different taste-masking approaches and formulation concepts were screened in vitro for candidate selection.


METHODS
Diclofenac was used as free acid. Five taste-masked microgranule formulations were prepared by wet granulation and/or coating processes, and compressed to ODTs. Citric acid (pH-modifying agent) and Eudragit® E PO (amino methacrylate copolymer) were used as taste-masking agents. Evaluation criteria were (i) disintegration time, (ii) processability and (iii) in-vitro dissolution profiles in simulated saliva (pH 7.4, 5 mL, 3 min) and compendial pH-change media (paddle, 50 rpm). The prototypes were compared to reference ODTs (without taste-masking). Most suitable ODT prototypes were selected and further evaluated for taste-masking efficiency using an electronic tongue.


CONCLUSIONS
In simulated saliva, the drug was slower released from the prototypes (between 1.1% and 15.5%) than from reference ODTs (23.7%). Less dissolved particles are thus expected in vivo for taste perception. Two ODT prototypes showed fast and complete drug release in phosphate buffer. The formulation providing the most efficient taste-masking was selected guided by electronic tongue data.


CONCLUSIONS
A novel palatable and fast acting diclofenac ODT formulation was successfully developed. Formulation design, development and in-vitro evaluation used in this study may serve as rational approach for manufacturing taste-masked orodispersible dosage forms.
Department of Pharmacy, Institute of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald , Greifswald , Germany .
Marie
M
Guhmann
Maren
M
Preis
Frédéric
F
Gerber
Norbert
N
Pöllinger
Jörg
J
Breitkreutz
Werner
W
Weitschies
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000032:analysis / Q000737:chemistry; D015374:Biosensing Techniques; D019343:Citric Acid / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000009:adverse effects* / Q000032:analysis / Q000737:chemistry; D004339:Drug Compounding; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008954:Models, Biological; D009061:Mouth Mucosa / Q000737:chemistry / Q000187:drug effects; D011109:Polymethacrylic Acids / Q000737:chemistry*; D012463:Saliva / Q000737:chemistry*; D013607:Tablets; D013649:Taste; D014059:Tongue / Q000737:chemistry / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005079:Excipients; D011109:Polymethacrylic Acids; D013607:Tablets; D004008:Diclofenac; D019343:Citric Acid; C518398:Eudragit E PO
Diclofenac; ODT; electronic tongue; taste; taste-masking