Influence of cyclodextrin complexation on piroxicam gel formulations

Department of Pharmaceutics Faculty of Pharmacy and Biochemistry University of Zagreb, Zagreb, Croatia.
Acta Pharmaceutica (Impact Factor: 0.91). 10/2005; 55(3):223-36.
Source: PubMed


The aim of this work was to evaluate the role of cyclodextrins in topical drug formulations. Solid piroxicam (PX) complexes with beta-cyclodextrin (beta-CD) and randomly methylated beta-cyclodextrin (RAMEB) were prepared by freeze-drying and characterized using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier transform infrared spectroscopy (FTIR) and near infrared spectroscopy (NIR). A physical mixture of PX and cyclodextrins was characterized by enhanced dissolution properties compared to the dissolution profile of the pure drug due to in situ complex formation. Formation of the PX-cyclodextrin inclusion complex additionally improved the drug dissolution properties. Influence of CDs on drug permeation from the water dispersion and the prepared hydroxypropyl methylcellulose (HPMC) gels was investigated. Permeation of the drug involved three consecutive processes: dissolution of the solid phase, diffusion across the swollen polymer matrix and drug permeation through the membrane. Complexation increased PX diffusion by increasing the amount of diffusible species in the donor phase. Slower drug diffusion through the HPMC matrix was the rate limiting step in the overall diffusion process. Possible interaction between the hydrophilic polymer and cyclodextrin may result in physicochemical changes, especially in a change of rheological parameters.

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    • "In the literature, some information is available on the enhancement of drug release from different topical bases using solid dispersion and inclusion complex techniques [18] [19] [20]. Ketoconazole (KET), an azole antifungal agent, is used to relieve the external symptoms (candidal vulvitis) of vaginal thrush (candidal vaginitis) but it has a poor aqueous solubility making it difficult to dissolve in water [2]. "
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    ABSTRACT: Solid dispersions of a slightly water-soluble drug, clotrimazole, were prepared in different weight ratios using polyethyleneglycol 4000 and different molecular weight polyvinyl pyrrolidones as carriers. Moreover, binary and ternary β-cyclodextrin complexes were prepared in different molar ratios. Both solid dispersions and β-cyclodextrin complexes were prepared by solvent evaporation technique. A phase solubility method was used to evaluate the effect of the tested carriers on the aqueous solubility of clotrimazole. The dissolution of all the preparations was tested using the USP paddle method. The selected solid dispersions and inclusion complexes were characterized by differential scanning calorimetry and X-ray powder diffractometry studies, and results clarified the role of the tested carriers in decreasing the crystallinity of clotrimazole and complexing abilities. Based on physical characters and in vitro drug release pattern, polyvinylpyrrolidone solid dispersions (1:1 weight ratio) and ternary cyclodextrin complexes (clotrimazole-β-cyclodextrin complexes with either polymer, 1:1 molar ratio) were selected as ideal batches for suppositories. Suppocire AM/50 mg carbopol 940, was chosen as a suppository base and the suppositories were prepared by molding technique. The prepared suppositories were characterized for weight variation, softening time and drug content. All these properties were found to be ideal. The in vitro drug release pattern was determined in citrate buffer (pH 4.5) containing 1% sodium lauryl sulfate. The in vitro release of clotrimazole from its solid dispersions and inclusion complexes incorporated suppositories was markedly improved when compared to the intact drug incorporated suppositories. Polyvinyl pyrrolidone solid dispersions incorporated suppositories were found to possess excellent antifungal activity.
    Full-text · Article · Sep 2011 · Indian Journal of Pharmaceutical Sciences
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    • "CDs enhance the solubility of nonpolar substances by non-covalent incorporation of the lipophilic portion of the molecule into their hydrophobic cavity (Bender and Komiyama, 1978).CDs are cyclic oligosaccharides consisting of 6, 7, or 8 glucose units linked through α-1,4-glucosidic bonds yielding α-β-, and γ-CD, respectively. They have been used to as carrier to deliver hydrophobic substances including long-and short-chain fatty acids, hormones, and drugs (Vicanova et al., 1999;Biddy et al., 2000;Pfitzner et al., 2000;Ulloth et al., 2003;Loftsson et al., 2006;Cappello et al., 2006;Miro et al., 2004;Jug et al., 2005). Early studies reported only minimal toxicity for CDs used to deliver lipophilic substances to cells in culture (Keller and Simons, 1998;Epa et al., 2000) as well as in the intrathecal/intracerebral delivery of hydrophobic drugs (Yaksh et al., 1991;Jang et al., 1992;Yamamoto and Yaksh, 1992). "
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    ABSTRACT: Cyclodextrins (CDs) are used to deliver hydrophobic molecules in aqueous environments. Methyl-beta-cyclodextrin (MbetaCD), a member of this family of molecules, has been proposed to be a good carrier to deliver fatty acids to cells in culture. This report focuses on studying the in vitro effects of MbetaCD on nerve growth factor-differentiated PC12 (NGFDPC12) cells, a tissue culture model to study neuronal survival and differentiation. The main findings are: (1) NGFDPC12 cells have normal viability when exposed to 0.12% MbetaCD but showed a significant loss in cell viability at higher concentrations; (2) NGFDPC12 cells exposed to 0.25% MbetaCD exhibit nuclear condensation, blebbing and apoptotic bodies, and whole cell lysates exhibited an increase in caspase-3-like activity and high levels of Bax and Bcl-X(L) protein expression compared to control. Cultures treated with 0.25% MbetaCD also showed cleavage of normal 21-kDa Bax protein into a 18-kDa fragment. (3) Experiments using 0.12% MbetaCD to deliver oleic acid did not affect cell viability, in contrast NGFDPC12 cultures in which 0.25% MbetaCD concentration is used exhibited similar loss of cell viability as observed with 0.25% MbetaCD alone. Treating these cultures with caspase-3 inhibitor z-VAD-fmk did not protect the cells from MbetaCD toxic effects. (4) Immortalized Schwann cells (iSC) exposed to MbetaCD 0.12% did not show loss of cell viability while 0.25% MbetaCD triggered a significant toxicity but with a different dose and time course dynamic than NGFDPC12 cells. Thus, NGFDPC12 or iSC cell cultures exposed to 0.12% MbetaCD exhibits normal viability while higher concentrations increase in cell death and apoptosis.
    Full-text · Article · Jun 2007 · NeuroToxicology
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