COMPLEXATION OF NAPROXEN WITH BETA-CYCLODEXTRIN WITH AND WITHOUT POLOXAMER 407 TO ENHANCE DRUG DISSOLUTION
Amal A. Elkordy1*, Amin Ashoore1 and Ebtessam A. Essa2,3
1. University of Sunderland, Department of Pharmacy, Health and Well-being, Sunderland, SR1 3SD, UK
2. Faculty of Pharmacy, Tanta University, Tanta, Egypt
3. Faculty of Pharmacy, Am El-Qura University, Saudi Arabia
Keywords: Dissolution enhancement, Naproxen, freeze drying, cyclodextrins, poloxamer-407
Non steroidal anti-inflammatory drugs (NSAID) have adverse effects on stomach. The histological appearance of affected mucosal cells ranging from mild to sever inflammation. Accordingly, the purpose of this study was to investigate the effects of: (i) ß-cyclodextrin (ß-CD), Poloxamer-407 (PLX) and sorbitol (Sorb) as carriers and (ii) freeze drying and physical mixing as techniques on solubility and dissolution of a model poorly water soluble NSAID drug, Naproxen (Nap) for the ultimate aim to avoid gastric discomfort via enhancement drug release. Therefore, two binary drug/carrier (1:1 and 1:4 w/w Nap/carrier ratios) combinations were prepared. The effect of multicomponent carrier systems, using ternary physical mixtures of Nap with ß-CD and PLX on the drug solubility and dissolution were also studied. All formulations were characterized using solubility, content uniformity, dissolution studies, Fourier transform infra-red (FT-IR) spectroscopy, and differential scanning calorimetry (DSC). All tested Nap/ combinations showed enhancement in drug release compared to pure drug, except Sorb that show a slight improvement only at high sugar concentration. Ternary Nap combinations showed the highest improvement of drug dissolution, compared to binary ones. Freeze dried formulations showed a marked enhancement in drug release especially in the first few minutes, compared to physical mixtures. Thermal studies indicated a reduction in drug crystallinity with freeze dried samples giving a higher amorphous yield obtained compared to binary physical mixtures.