A FACTORIAL STUDY ON ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF LORNOXICAM EMPLOYING HP-β-CYCLODEXTRIN AND SURFACTANTSAbstract
Lornoxicam, a widely prescribed anti-inflammatory and analgesic drug belongs to class II under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. It is practically insoluble in water and aqueous fluids. As such its oral absorption is dissolution rate limited and it requires enhancement in solubility and dissolution rate for increasing its oral bioavailability. The objective of the present study is to enhance the solubility and dissolution rate of lornoxicam employing Hydroxy propyl β-cyclodextrin (HPβCD) and two surfactants (SLS and Tween 80) alone and in combination. The individual main effects and combined (interaction) effects of HPβ-cyclodextrin and surfactants on the solubility and dissolution rate of lornoxicam were evaluated in a series of 22 factorial experiments. The solubility of lornoxicam in the four selected fluids as per 22 factorial study in each case was determined (n=4). Lornoxicam-βCD-surfactant inclusion complexes were prepared employing the selected combinations of HPβCD and surfactant in each case as per a 22 factorial design and the inclusion complexes prepared were evaluated for dissolution rate and dissolution efficiency. Combination of Hydroxy propyl βCD with surfactants, SLS and Tween 80 has resulted in a much higher enhancement in the solubility of lornoxicam than is possible with them individually. ANOVA indicated that the individual main effects of HPβCD, SLS and Tween 80 as well as the combined effects in enhancing the solubility and dissolution rate of lornoxicam are highly significant (P<0.01). HPβCD alone gave 1.53 fold increase in the solubility of lornoxicam. Whereas in combination with SLS and Tween 80 it gave respectively 31.43 and 13.20 fold increase in the solubility of lornoxicam. Lornoxicam- HPβCD and lornoxicam- HPβCD- Surfactant complexes gave rapid and higher dissolution of lornoxicam when compared to lornoxicam pure drug. HPβCD alone gave an increase of 4.35 fold in the dissolution rate (K1) of lornoxicam. Combination of HPβCD with SLS and Tween 80 has further enhanced the dissolution rate (K1) of lornoxicam by 9.50 and 6.10 folds respectively. Hence, a combination of HPβCD with surfactants (SLS and Tween 80) is recommended for enhancing the solubility and dissolution rate of lornoxicam, a poorly soluble BCS Class II drug.
S.Z. Chemate* and K.P.R. Chowdary
Padmashri Dr. Vitthalrao Vikhe Patil Foundation’s College of Pharmacy, Vilad Ghat, Ahmednagar-414111, Maharashra, India
18 March, 2012
25 April, 2012
22 June, 2012
01 July 2012