The effect of using two NSAIDs with different solubility on freeze drying technology

Different non-steroidal anti- inflammatory drugs (NSAIDs) are present in the market with different properties. Two NSAIDs with different solubilities have been selected to study the effect of freeze drying technology on them. Aceclofenac, a water insoluble NSAID, and Diclofenac Potassium, a water soluble NSAID, were taken as candidates for enhancement of in-vitro dissolution and in-vivo bioavailability; through formulation of orally disintegrating tablet using freeze drying technology. An aqueous dispersion of Aceclofenac (or Diclofenac Potassium), matrix former, filler (sugar alcohol), and an anti-collapse was adopted to prepare freeze dried tablet formulations. The tablets were evaluated compendial (uniformity of weight, uniformity of content, friability, in-vitro disintegration time and in-vitro dissolution) and non-compendial (wetting time and in-vivo disintegration time). The compendial results showed that both freeze dried tablet formulations of Aceclofenac and also Diclofenac Potassium disintegrated within few seconds and showed significantly faster dissolution rate in comparison with both immediate release tablet formulae Aceclofenac tablet (Bristaflam®) and Diclofenac Potassium tablet (Cataflam®). In-vivo evaluation for the best chosen Aceclofenac and Diclofenac Potassium ODT formulations (LA#10) and (LD#11), respectively was done for determination of the drug pharmacokinetics in comparison with the immediate release tablet formulations. A randomized crossover design was adopted in the comparative bioavailability study done on four healthy volunteers. Statistical analysis revealed significant difference between the Bristaflam immediate release tablet and Aceclofenac ODT (LA#10) regarding the following pharmacokinetic parameters: Cmax, Tmax, t1/2, AUC(0–24), AUC(0-”) (p 0.05). The relative bioavailability of the Aceclofenac ODT (LA# 10) was 186.12% relative to the IR tablet (Bristaflam®) taken as reference standard. However, statistical analysis revealed significant difference between the Cataflam immediate release tablet and Diclofenac Potassium ODT (LD#11) regarding the following pharmacokinetic parameters: Cmax and Tmax (p 0.05). The relative bioavailability of the Diclofenac Potassium ODT (LD#11) was 101.09% relative to the immediate release tablet (Cataflam®) taken as reference product. Though a significant decrease in the time of onset of action; however no significant increase in the relative bioavailability was observed. Though, both drugs showed increased rate of absorption, however the insoluble NSAID (Aceclofenac) showed higher bioavailability than the soluble NSAID (Diclofenac Potassium). The impact of the relative solubility factor was highly significant on the bioavailability though using the same technology.