PURPOSE: For poorly soluble, highly permeable (Class II) drugs, such as indomethacin, the rate of oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Therefore together with the permeability, the solubility and dissolution behaviour of a drug are key determinants of its oral bioavailability. The object of the present study is to increase dissolution rate of indomethacin using liquisolid compacts. METHODS: Several formulations of liquisolid compacts containing various ratios of drug: propylene glycol (ranging from 1:1 to 1:4) was prepared. In this study the ratio of microcrystalline cellulose (carrier) to silica (coating powder material) was 20 in all formulations. The dissolution behaviour of indomethacin from liquisolid compacts and conventional formulations was investigated at different pHs (1.2 and 7.2). RESULTS: The results showed that liquisolid compacts demonstrated considerably higher drug dissolution rates than those of conventionally made capsules and directly compressed tablets containing indomethacin. This was due to increased wetting properties and surface of drug available for dissolution. Also it has been shown that the fraction of molecularly dispersed drug (FM) in the liquid medication of liquisolid systems was directly proportional to their indomethacin dissolution rates (DR). An attempt was made to correlate the percentage drug dissolved in 10-min with the solubility of indomethacin in different vehicles. A plot of the percentage drug dissolved against the solubility of indomethacin showed that the amount of drug dissolved increased linearly (correlation coefficient of 0.9994 and 0.996 at pH 7.2 and 1.2 respectively) with an increase in solubility of indomethacin in the vehicles. CONCLUSION: The liquisolid compacts technique can be a promising alternative for the formulation of water insoluble drugs, such as indomethacin into rapid release tablets.
PURPOSE: For poorly soluble, highly permeable (Class II) drugs, such as indomethacin, the rate of oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Therefore together with the permeability, the solubility and dissolution behaviour of a drug are key determinants of its oral bioavailability. The object of the present study is to increase dissolution rate of indomethacin using liquisolid compacts. METHODS: Several formulations of liquisolid compacts containing various ratios of drug: propylene glycol (ranging from 1:1 to 1:4) was prepared. In this study the ratio of microcrystalline cellulose (carrier) to silica (coating powder material) was 20 in all formulations. The dissolution behaviour of indomethacin from liquisolid compacts and conventional formulations was investigated at different pHs (1.2 and 7.2). RESULTS: The results showed that liquisolid compacts demonstrated considerably higher drug dissolution rates than those of conventionally made capsules and directly compressed tablets containing indomethacin. This was due to increased wetting properties and surface of drug available for dissolution. Also it has been shown that the fraction of molecularly dispersed drug (FM) in the liquid medication of liquisolid systems was directly proportional to their indomethacin dissolution rates (DR). An attempt was made to correlate the percentage drug dissolved in 10-min with the solubility of indomethacin in different vehicles. A plot of the percentage drug dissolved against the solubility of indomethacin showed that the amount of drug dissolved increased linearly (correlation coefficient of 0.9994 and 0.996 at pH 7.2 and 1.2 respectively) with an increase in solubility of indomethacin in the vehicles. CONCLUSION: The liquisolid compacts technique can be a promising alternative for the formulation of water insoluble drugs, such as indomethacin into rapid release tablets.
Authors: Peng Liu; Odile De Wulf; Johanna Laru; Teemu Heikkilä; Bert van Veen; Juha Kiesvaara; Jouni Hirvonen; Leena Peltonen; Timo Laaksonen Journal: AAPS PharmSciTech Date: 2013-04-25 Impact factor: 3.246