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Piroxicam/β-cyclodextrin complex included in cellulose derivatives-based matrix microspheres as new solid dispersion-controlled release formulations

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Abstract

New formulations capable to enhance piroxicam (PRX) water solubility and at the same time to control and adjust its release have been developed. For this purpose, two methods have been used and combined to achieve this goal, namely complexation and microencapsulation by O/W emulsion solvent evaporation. In order to modify the drug release, first, microparticles composed of pure PRX and ethylcellulose (EC) or mixtures of EC and hydroxypropylmethylcellulose (HPMC) were prepared, and then, other micropaticles containing the β-cyclodextrin/piroxicam (β-CD/PRX) complex obtained by the solvent evaporation technique and EC or a mixture of EC and HPMC were produced and tested. These formulations were characterized by FT-IR, XRD, optical microscopy, and SEM methods. Drug dissolution tests were carried out in acidic media at pH = 1.2 and 37°C. Depending on the microparticles composition, their size (d10) ranged between 49 μ.m and 121 μ.m and PRXloaded varied from 10.8 % to 27.7 %. The effect of complexation and HPMC polymer on the drug release was investigated; the results demonstrated that the Higuchi’s release constant significantly increased when using the EC/HPMC mixture as a matrix with pure PRX or only EC as a matrix with the β-CD/PRX complex. The results are remarkably promising since the combination of these processes provided new SD-CR formulations of piroxicam which enabled simultaneous enhancement and control of its release from the carriers.

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References

  • Aejaz, A., & Sadath, A. (2013). Development and characterization of floating microspheres of clarithromycin as gastro retentive dosage form. International Research Journal of Pharmacy, 4(1), 165–168.

    CAS  Google Scholar 

  • Agarwal, S., Wendorff, J. H., & Greiner, A. (2008). Use of elec trospinning technique for biomedical applications. Polymer, 49, 5603–5621. DOI: 10.1016/j.polymer.2008.09.014.

    Article  CAS  Google Scholar 

  • Aquino, R. P., Auriemma, G., d’Amore, M., D’Ursi, A. M., Mencherini, T., & Del Gaudio, P. (2012). Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique: Morphology and drug release. Carbohydrate Polymers, 89, 740–748. DOI: 10.1016/j.carbpol.2012.04.003.

    Article  CAS  Google Scholar 

  • Berkland, C., Kim, K. K., & Pack, D. W. (2003). PLG microsphere size controls drug release rate through several competing factors. Pharmaceutical Research, 20, 1055–1062. DOI: 10.1023/a: 1024466407849.

    Article  CAS  Google Scholar 

  • Bertoluzza, A., Rossi, M., Taddei, P., Redenti, E., Zanol, M., & Ventura, P. (1999). FT-Raman and FT-IR studies of 1:2.5 piroxicam: fi-cyclodextrin inclusion compound. Journal of Molecular Structure, 480–481, 535–539. DOI: 10.1016/s0022-2860(98)00734–0.

    Article  Google Scholar 

  • Bibby, D. C., Davies, N. M., & Tucker, I. G. (2000). Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems. International Journal of Pharmaceutics, 197, 1–11. DOI: 10.1016/s0378–5173(00)00335–5.

    Article  CAS  Google Scholar 

  • Bouchal, F., Skiba, M., Chaffai, N., Hallouard, F., Fatmi, S., & Lahiani-Skiba, M. (2015). Fast dissolving cyclodextrin complex of piroxicam in solid dispersion Part I: Influence of fi-CD and HPfi-CD on the dissolution rate of piroxicam. International Journal of Pharmaceutics, 478, 625–632. DOI: 10.1016/j.ijpharm.2014.12.019.

    Article  CAS  Google Scholar 

  • Brunton, L. L., Chabner, B. A., & Knollman, B. C. (2011). Goodman and Gilman’s the pharmacological basis of therapeutics (12th ed.). New York, NY, USA: McGraw-Hill Medical.

    Google Scholar 

  • Canto, G. S., Dalmora, S. L., & Oliveira, A. G. (1999). Piroxicam encapsulated in liposomes: Characterization and in vivo evaluation of topical anti-inflammatory effect. Drug Development and Industrial Pharmacy, 25, 1235–1239. DOI: 10.1081/ddc-100102293.

    Article  CAS  Google Scholar 

  • Challa, R., Ahuja, A., Ali, J., & Khar, R. K. (2005). Cyclodextrins in drug delivery: An updated review. AAPS Pharm-Sci Tech, 6, E329–E357. DOI: 10.1208/pt060243.

    Article  Google Scholar 

  • Chaudhary, A., Nagaich, U., Gulati, N., Sharma, V. K., & Khosa, R. L. (2012). Enhancement of solubilization and bioavailability of poorly soluble drugs by physical and chemical modifications: A recent review. Journal of Advanced Pharmacy Education & Research, 2, 32–67.

    Google Scholar 

  • Cilurzo, F., Selmin, F., Minghetti, P., Rimoldi, I., Demartin, F., & Montanari, L. (2005). Fast-dissolving mucoadhesive microparticulate delivery system containing piroxicam. European Journal of Pharmaceutical Sciences, 24, 355–361. DOI: 10.1016/j.ejps.2004.11.010.

    Article  CAS  Google Scholar 

  • Del Valle, E. M. M. (2004). Cyclodextrins and their uses: a review. Process Biochemistry, 39, 1033–1046. DOI: 10.1016/ s0032–9592(03)00258–9.

    Article  CAS  Google Scholar 

  • Diaf, K., El Bahri, Z., Chafi, N., Belarbi, L., & Mesli, A. (2012). Ethylcellulose, polycaprolactone, and eudragit matrices for controlled release of piroxicam from tablets and microspheres. Chemical Papers, 66, 779–786. DOI: 10.2478/s11696–012–0191-x.

    Article  CAS  Google Scholar 

  • Dukic-Ott, A., Remon, J. P., Foreman, P., & Vervaet, C. (2007). Immediate release of poorly soluble drugs from starch- based pellets prepared via extrusion/spheronisation. European Journal of Pharmaceutics and Biopharmaceutics, 67, 715–724. DOI: 10.1016/j.ejpb.2007.04.014.

    Article  CAS  Google Scholar 

  • Escandar, G. M. (1999). Spectrofluororimetric determination of piroxicam in the presence and absence of fi-cyclodextrin. Analyst, 124, 587–591. DOI: 10.1039/a809180c.

    Article  CAS  Google Scholar 

  • Filipovic-Grcic, J., Becirevic-Lacan, M., Skalkom, N., & Jalsenjak, I. (1996). Chitosan microspheres of nifedipine and nifedipine-cyclodextrin inclusion complexes. International Journal of Pharmaceutics, 135, 183–190. DOI: 10.1016/0378-5173(96)04470–5.

    Article  CAS  Google Scholar 

  • Freiberg, S., & Zhu, X. X. (2004). Polymer microspheres for controlled drug release. International Journal of Pharmaceutics, 282, 1–18. DOI: 10.1016/j.ijpharm.2004.04.013.

    Article  CAS  Google Scholar 

  • Ghosal, K., Chakrabarty, S., & Nanda, A. (2011). Hydrox- ypropyl methylcellulose in drug delivery. Der Pharmacia Sinica, 2(2), 152–168.

    CAS  Google Scholar 

  • Higuchi, T. (1963). Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. Journal of Pharmaceutical Sciences, 52, 1145–1149. DOI: 10.1002/jps.2600521210.

    Article  CAS  Google Scholar 

  • Joseph, N. J., Lakshmi, S., & Jayakrishnan, A. (2002). A floating-type oral dosage form for piroxicam based on hollow polycarbonate microspheres: in vitro and in vivo evaluation in rabbits. Journal of Controlled Release, 79, 71–79. DOI: 10.1016/s0168–3659(01)00507–7.

    Article  CAS  Google Scholar 

  • Jug, M., & Becirevic-Lacan, M. (2004). Influence of hydroxypropyl-fi-cyclodextrin complexation on piroxicam release from buccoadhesive tablets. European Journal of Pharmaceutical Sciences, 21, 251–260. DOI: 10.1016/j.ejps.2003.10.029.

    Article  CAS  Google Scholar 

  • Jug, M., Becirevic-Lacan, M., Kwokal, A., & Cetina-Cizmek, B. (2005). Influence of cyclodextrin complexation on piroxicam gel formulations. Acta Pharmaceutica, 55, 223–236.

    CAS  Google Scholar 

  • Jyothi, N. V. N., Prasanna, P. M., Sakarkar, S. N., Prabha, K. S., Ramaiah, P. S., & Srawa, G. Y. (2010). Microencapsulation techniques, factors influencing encapsulation efficiency. Journal of Microencapsulation: Micro and Nano Carriers, 27, 187–197. DOI: 10.3109/02652040903131301.

    Article  CAS  Google Scholar 

  • Kibbe, A. H. (2000). Handbook of pharmaceutical excipients (3rd ed.). Washington, DC, USA: American Pharmacists Association.

    Google Scholar 

  • Kim, Y. H., Cho, D. W., Kang, S. G., Yoon, M. J., & Kim, D. H. (1994). Excited-state intramolecular proton transfer emission of piroxicam in aqueous fi-cyclodextrin solutions. Journal of Luminescence, 59, 209–217. DOI: 10.1016/0022-2313(94)90043–4.

    Article  CAS  Google Scholar 

  • Korsmeyer, R. W., & Peppas, N. A. (1983). Macromolecular and modeling aspects of swelling-controlled systems. In T. J. Roseman, & S. Z. Mansdorf (Eds.), Controlled release delivery systems (pp. 77–90). New York, NY, USA: Marcel Dekker.

    Google Scholar 

  • Lai, F., Pini, E., Angioni, G., Manca, M. L., Perricci, J., Sinico, C., & Fadda, A. M. (2011). Nanocrystals as tool to improve piroxicam dissolution rate in novel orally disintegrating tablets. European Journal of Pharmaceutics and Biopharmaceutics, 79, 552–558. DOI: 10.1016/j.ejpb.2011.07.005.

    Article  CAS  Google Scholar 

  • Lee, C. R., & Balfour, J. A. (1994). Piroxicam-fi-cyclodextrin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in rheumatic diseases and pain states. Drugs, 48, 907–929. DOI: 10.2165/00003495199448060–00007.

    Article  CAS  Google Scholar 

  • Loh, Z. H., Samanta, A. K., & Sia Heng, P. W. (2015). Overview of milling techniques for improving the solubility of poorly water soluble drugs. Asian Journal of Pharmaceutical Sciences, 10, 255–274. DOI: 10.1016/j.ajps.2014.12.006.

    Article  Google Scholar 

  • Lu, X. F., Wang, C., & Wei, Y. (2009). One-dimensional composite nanomaterials: Synthesis by electrospinning and their applications. Small, 5, 2349–2370. DOI: 10.1002/smll.200900 445.

    Article  CAS  Google Scholar 

  • Moffat, A. C., Osselton, M. D., & Widdop, B. (2004). Clarke’s analysis of drugs and poisons (3rd ed). London, UK: Pharmaceutical Press.

    Google Scholar 

  • Moldenhauer, M. G., & Nairn, J. G. (1990). Formulation parameters affecting the preparation and properties of microencapsulated ion-exchanged resins containing theophylline. Journal of Pharmaceutical Sciences, 79, 659–666. DOI: 10.1002/jps.2600790802.

    Article  CAS  Google Scholar 

  • Mostafa Kamal, M. A. H., Ahmed, M., Ibne Wahed, M. I., Shah Amran, M., Shaheen, S. M., Rashid, M., & Anwar-Ul-Islam, M. (2008). Development of indomethacin sustained release microcapsules using ethyl cellulose and hydroxy propyl methyl cellulose phthalate by O/W emulsification. Dhaka University Journal of Pharmaceutical Sciences, 7, 83–88. DOI: 10.3329/dujps.v7i1.1223.

    Google Scholar 

  • Mura, P. (2015). Analytical techniques for characterization of cyclodextrin complexes in the solid state: A review. Journal of Pharmaceutical and Biomedical Analysis, 113, 226–238. DOI: 10.1016/j.jpba.2015.01.058.

    Article  CAS  Google Scholar 

  • Nagabhushanam, M. V. (2010). Formulation studies on cy-clodextrin complexes of piroxicam. Rasayan Journal of Chemistry, 3, 314–320.

    CAS  Google Scholar 

  • Paaver, U., Lust, A., Mirza, S., Rantanen, J., Veski, P., Heinämäki, J., & Kogermann, K. (2012). Insight into the solubility and dissolution behavior of piroxicam anhydrate and monohydrate forms. International Journal of Pharmaceutics, 431, 111–119. DOI: 10.1016/j.ijpharm.2012.04.042.

    Article  CAS  Google Scholar 

  • Paaver, U., Heinämäki, J., Kassamakov, I., Hægström, E., Ylitalo, T., Nolvi, A., Kozlova, J., Laidmae, I., Kogermann, K., & Veski, P. (2014). Nanometer depth resolution in 3D topographic analysis of drug-loaded nanofibrous mats without sample preparation. International Journal ofPharmaceutics, 462, 29–37. DOI: 10.1016/j.ijpharm.2013.12.041.

    Article  CAS  Google Scholar 

  • Paaver, U., Heinämäki, J., Laidmae, I., Lust, A., Kozlova, J., Sillaste, E., Kirsimae, K., Veski, P., & Kogermann, K. (2015). Electrospun nanofibers as a potential controlled- release solid dispersion system for poorly water-soluble drugs. International Journal of Pharmaceutics, 479, 252–260. DOI: 10.1016/j.ijpharm.2014.12.024.

    Article  CAS  Google Scholar 

  • Patil, J. S., Kadam, D. V., Marapur, S. C., & Kamalapur, M. V. (2010). Inclusion complex system; a novel technique to improve the solubility and bioavailability of poorly soluble drugs: A review. International Journal of Pharmaceutical Sciences Review and Research, 2(2), 29–34.

    CAS  Google Scholar 

  • Pelipenko, J., Kristl, J., Janković, B., Baumgartner, S., & Kocbek, P. (2013). The impact of relative humidity during electrospinning on the morphology and mechanical properties of nanofibers. International Journal of Pharmaceutics, 456, 125–134. DOI: 10.1016/j.ijpharm.2013.07.078.

    Article  CAS  Google Scholar 

  • Phalguna, Y., Venkateshwarlu, B. S., Gudas, G. K., & Debnath, S. (2010). HPMC microspheres of zidovudine for sustained release. International Journal of Pharmacy and Pharmaceutical Sciences, 2(Suppl 4), 41–43.

    CAS  Google Scholar 

  • Phutane, P., Shidhaye, S., Lotlikar, V., Ghule, A., Sutar, S., & Kadam, V. (2010). In vitro evaluation of novel sustained release microspheres of glipizide prepared by the emulsion solvent diffusion-evaporation method. Journal of Young Pharmacists, 2, 35–41. DOI: 10.4103/0975–1483.62210.

    Article  CAS  Google Scholar 

  • Piao, M. G., Yang, C. W., Li, D. X., Kim, J. O., Jang, K. Y., Yoo, B. K., Kim, J. A., Woo, J. S., Lyoo, W. S., Han, S. S., Lee, Y. B., Kim, D. D., Yong, C. S., & Choi, H. G. (2008). Preparation and in vivo evaluation of piroxicam- loaded gelatin microcapsule by spray drying technique. Biological and Pharmaceutical Bulletin, 31, 1284–1287. DOI: 10.1248/bpb.31.1284.

    Article  CAS  Google Scholar 

  • Raut, N. S., Somvanshi, S., Jumde, A. B., Khandelwal, H. M., Umekar, M. J., & Kotagale, N. R. (2013). Ethyl cellulose and hydroxypropyl methyl cellulose buoyant microspheres of metoprolol succinate: Influence of pH modifiers. International Journal of Pharmaceutical Investigation, 3, 163–170. DOI: 10.4103/2230–973x.119235.

    Article  Google Scholar 

  • Redenti, E., Peveri, T., Zanol, M., Ventura, P., Gnappi, G., & Montenero, A. (1996). A study on the differentiation between amorphous piroxicam:β-cyclodextrin complex and a mixture of the two amorphous components. International Journal of Pharmaceutical Science, 129, 289–294. DOI: 10.1016/0378-5173(95)04357-g.

    Article  CAS  Google Scholar 

  • Rozou, S., Voulgari, A., & Antoniadou-Vyza, E. (2004). The effect of pH dependent molecular conformation and dimerization phenomena of piroxicam on the drug:cyclodextrin complex stoichiometry and its chromatographic behaviour: A new specific HPLC method for piroxicam:cyclodextrin formulations. European Journal of Pharmaceutical Sciences, 21, 661–669. DOI: 10.1016/j.ejps.2004.01.007.

    Article  CAS  Google Scholar 

  • Saravanan, M., & Anupama, B. (2011). Development and evaluation of ethylcellulose floating microspheres loaded with ranitidine hydrochloride by novel solvent evaporation-matrix erosion method. Carbohydrate Polymers, 85, 592–596. DOI: 10.1016/j.carbpol.2011.03.020.

    Article  CAS  Google Scholar 

  • Savjani, K. T., Gajjar, A. K., & Savjani, J. K. (2012). Drug solubility: Importance and enhancement techniques. ISRN Pharmaceutics, 2012, 195–727. DOI: 10.5402/2012/195727.

    Article  Google Scholar 

  • Scarpignato, C. (2013). Piroxicam-β-cyclodextrin: A GI safer piroxicam. Current Medicinal Chemistry, 20, 2415–2437. DOI: 10.2174/09298673113209990115.

    Article  CAS  Google Scholar 

  • Srivastava, A. K., Ridhurkar, D. N., & Wadhwa, S. (2005). Floating microspheres of cimetidine: Formulation, characterization and in vitro evaluation. Acta Pharmaceutica, 55, 277–285.

    CAS  Google Scholar 

  • Taepaiboon, P., Rungsardthong, U., & Supaphol, P. (2006). Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs. Nanotechnology, 17, 2317–2329. DOI: 10.1088/0957–4484/17/9/041.

    Article  CAS  Google Scholar 

  • Tran, P. H. L., Tran, T. T. D., Park, J. B., & Lee, B. J. (2011). Controlled release systems containing solid dispersions: Strategies and mechanisms. Pharmaceutical Research, 28, 2353–2378. DOI: 10.1007/s11095–011–0449-y.

    Article  CAS  Google Scholar 

  • Turro, N. J., Okubo, T., & Chung, C. J. (1982). Analysis of static and dynamic host-guest associations of detergents with cyclodextrins via photoluminescence methods. Journal of the American Chemical Society, 104, 1789–1794. DOI: 10.1021/ja00371a001.

    Article  CAS  Google Scholar 

  • Wade, A., & Weller, P. J. (1994). Handbook of pharmaceutical excipients (2nd ed.). Washington, DC, USA: American Pharmaceutical Association.

    Google Scholar 

  • Wagenaar, B. W., & Muller, B. W. (1994). Piroxicam release from spray-dried biodegradable microspheres. Biomaterials, 15, 49–54. DOI: 10.1016/0142–9612(94)90196–1.

    Article  CAS  Google Scholar 

  • Wen, H., & Park, K. N. (Eds.) (2010). Oral controlled release formulation design and drug delivery: Theory and practice. Hoboken, NJ, USA: Wiley.

    Book  Google Scholar 

  • Xua, Q. X., Chin, S. E., Wang, C. H., & Pack, D. W. (2013). Mechanism of drug release from double-walled PDLLA(PLGA) microspheres. Biomaterials, 34, 3902–3911. DOI: 10.1016/j.biomaterials.2013.02.015.

    Article  Google Scholar 

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Khoukhi, O.E., Bahri, Z.E., Diaf, K. et al. Piroxicam/β-cyclodextrin complex included in cellulose derivatives-based matrix microspheres as new solid dispersion-controlled release formulations. Chem. Pap. 70, 828–839 (2016). https://doi.org/10.1515/chempap-2016-0014

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