Purpose: The existence of a drug percolation threshold above which the behaviour of a dosage form undergoes a step change is well reported (Leuenberger 1999). In this study, we investigated two aspects related to the influence of a percolation threshold on the dissolution behaviour of ibuprofen from tablets composed of binary blends of ibuprofen and microcrystalline cellulose (MCC). The first aspect was to identify the step change in dissolution behaviour of ibuprofen from these compacts, above and below the percolation threshold. The second aspect was to investigate whether differences in MCC quality would alter the percolation threshold and dissolution behaviour.
Methods: Binary blends of Ibuprofen (1-30%w/w loading) and MCC were compressed. Two different MCC grades: Vivapur®102, air-stream dried quality, and Emcocel®90, spray-dried quality, were compared. These grades have similar average particles size but differ in morphology and particle size distribution. Dissolution studies were performed on tablets of similar tensile strength (2-3 MPa) using a type II dissolution apparatus; the dissolution medium of phosphate buffer pH-7.2. Tablets disintegration was studied in deionised water using a novel technique Broadband Acoustic Resonance Spectroscopy (BARDS).
Results: Figure 1 shows the dissolution profiles for blends studied. The percolation threshold for both blends was identified to be between 15 and 20% ibuprofen w/w. At lower Ibuprofen concentrations (<15%), both Emcocel and Vivapur blends show a comparable drug release rate. Above the percolation threshold, a more prolonged ibuprofen release was observed differences in tablet dissolution were noted between tablets produced from Vivapur®102 and Emcocel®90. BARDS analysis of the tablets provided insights into differences in the wetting of drug particles following the initial disintegration period which supported the dissolution behaviour.
Conclusion: The dissolution behaviour of Ibuprofen/MCC tablets was influenced by both the Ibuprofen concentration relative to the percolation threshold and the grade of MCC above the percolation threshold. BARDS spectra provided a valuable insight into the initial stages of the dissolution process following disintegration.