Abstract
The purpose of the present investigation was to analyze devitrification of amorphous drugs such as lornoxicam, meloxicam, and felodipine in the presence of sericin. The binary solid dispersions comprising varying mass ratios of drug and sericin were subject to amorphization by spray drying, solvent evaporation, ball milling, and physical mixing. Further, obtained solid dispersions (SDs) were characterized by HPLC, ATR-FTIR, H1NMR, molecular docking, accelerated stability study at 40°C and 75 ± 2% RH (XRD and DSC), and in vitro dissolution studies. The HPLC analysis indicated no decomposition of the drugs during the spray drying process. From ATR-FTIR, NMR, and molecular docking study, it was revealed that H-bonding played a vital role in amorphous drug stabilization. An excellent devitrification inhibition was observed in case of lornoxicam (SDLS3) and meloxicam (SDMS3) SDs prepared by spray drying. On the other hand, spray-dried SD of felodipine (SDFS3) showed traces of microcrystals. The percent crystallinity of SDLS3, SDMS3, and SDFS3 was found to be 7.4%, 8.23%, and 18.31% respectively indicating adequate amorphization. The dissolution performance of SDLS, SDMS, and SDFS after 3 months showed > 85% than SDs prepared by other methods. Thus, sericin significantly inhibited crystallization and was responsible for amorphous state stabilization of pharmaceuticals.
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Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50:47–60. http://www.ncbi.nlm.nih.gov/pubmed/10840192.
Serajuddln ATM. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci. 1999;88:1058–66.
Zhou D, Zhang GGZ, Law D, Grant DJW, Schmitt EA. Physical stability of amorphous pharmaceuticals: importance of configurational thermodynamic quantities and molecular mobility. J Pharm Sci. 2002;91:1863–72.
Graeser KA, Patterson JE, Zeitler JA, Gordon KC, Rades T. Correlating thermodynamic and kinetic parameters with amorphous stability. Eur J Pharm Sci. 2009;37:492–8.
Ahlneck C, Zografi G. The molecular basis of moisture effects on the physical and chemical stability of drugs in the solid state. Int J Pharm. 1990;62:87–95.
Yoshioka M, Hancock BC, Zografi G. Crystallization of lndomethacin from the amorphous state below and above its glass transition temperature. J Pharm Sci. 1994;83:1700–5.
Trasi NS, Purohit HS, Taylor LS. Evaluation of the crystallization tendency of commercially available amorphous tacrolimus formulations exposed to different stress conditions. Pharm Res. 2017;34:2142–55.
Baghel S, Cathcart H, O’Reilly NJ. Polymeric amorphous solid dispersions: a review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical classification system class II drugs. J Pharm Sci Elsevier Ltd. 2016;105:2527–44. Available from: https://doi.org/10.1016/j.xphs.2015.10.008.
Hancock B, Shamblin S, Zografi G. Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures. Pharm Res. 1995;12:799–806.
Pokharkar VB, Mandpe LP, Padamwar MN, Ambike AA, Mahadik KR, Paradkar A. Development, characterization and stabilization of amorphous form of a low Tg drug. Powder Technol. 2006;167:20–5.
Matsumoto T, Zografi G. Physical properties of solid molecular dispersions of indomethacin with poly (vinylpyrrolidone) and poly(vinylpyrrolidone-co-vinyl-acetate) in relation to indomethacin crystallization. Pharm Res. 1999;16:1722–8.
Pignatello R, Spadaro D, Vandelli MA, Forni F, Puglisi G. Characterization of the mechanism of interaction in ibuprofen-Eudragit RL100 coevaporates. Drug Dev Ind Pharm. 2004;30:277–88. http://www.ncbi.nlm.nih.gov/pubmed/15109027.
Shakhtshneider TP, De FDÀ, Capet F, Willart JF, Descamps M, S a M, et al. Grinding of drugs with pharmaceutical excipients at cryogenic temperatures part I. Cryogenic grinding of piroxicam – polyvinylpyrrolidone mixtures. J Therm Anal Calorim. 2007;89:699–707.
Shakhtshneider TP, Danède F, Capet F, Willart JF, Descamps M, Paccou L, et al. Grinding of drugs with pharmaceutical excipients at cryogenic temperatures. J Therm Anal Calorim. 2007;89:709–15.
Mulye SP, Jamadar SA, Karekar PS, Pore YV, Dhawale SC. Improvement in physicochemical properties of ezetimibe using a crystal engineering technique. Powder Technol Elsevier BV. 2012;222:131–8. Available from: https://doi.org/10.1016/j.powtec.2012.02.020.
Fu Q, Fang M, Hou Y, Yang W, Shao J, Guo M, et al. A physically stabilized amorphous solid dispersion of nisoldipine obtained by hot melt extrusion. Powder Technol. 2016;301:342–8.
Bhende S, Jadhav N. Moringa coagulant as a stabilizer for amorphous solids: part I. AAPS PharmSciTech. 2012;13:400–10. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3364398&tool=pmcentrez&rendertype=abstract.
Shilpi D, Kushwah V, Agrawal AK, Jain S. Improved stability and enhanced oral bioavailability of atorvastatin loaded stearic acid modified gelatin nanoparticles. Pharm Res. 2017;34:1505–16.
Van den Mooter G, Wuyts M, Blaton N, Busson R, Grobet P, Augustijns P, et al. Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25. Eur J Pharm Sci. 2001;12:261–9.
Knopp MM, Olesen NE, Holm P, Langguth P, Holm R, Rades T. Influence of polymer molecular weight on drug-polymer solubility: a comparison between experimentally determined solubility in PVP and prediction derived from solubility in monomer. J Pharm Sci. 2015;104:2905–12.
Zhang P, Forsgren J, Strømme M. Stabilisation of amorphous ibuprofen in Upsalite, a mesoporous magnesium carbonate, as an approach to increasing the aqueous solubility of poorly soluble drugs. Int J Pharm Elsevier BV. 2014;472:185–91. Available from: https://doi.org/10.1016/j.ijpharm.2014.06.025.
Lin S, Cheng C. Solid state interaction studies of drug-polymers (II): warfarin-Eudragit E, RL or S resins Shan-Yang. Eur J Pharm Sci. 1994;1:313–22.
Bley H, Fussnegger B, Bodmeier R. Characterization and stability of solid dispersions based on PEG/polymer blends. Int J Pharm Elsevier BV. 2010;390:165–73. Available from: https://doi.org/10.1016/j.ijpharm.2010.01.039.
Vasa DM, Dalal N, Katz JM, Roopwani R, Nevrekar A, Patel H, et al. Physical characterization of drug: polymer dispersion behavior in polyethylene glycol 4000 solid dispersions using a suite of complementary analytical techniques. J Pharm Sci. 2014;103:2911–23.
Ueda H, Aikawa S, Kashima Y, Kikuchi J, Ida Y, Tanino T, et al. Anti-plasticizing effect of amorphous indomethacin induced by specific intermolecular interactions with PVA copolymer. J Pharm Sci Elsevier Masson SAS. 2014;103:2829–38. Available from: https://doi.org/10.1002/jps.24023.
Shimpi SL, Chauhan B, Mahadik KR, Paradkar A. Stabilization and improved in vivo performance of amorphous etoricoxib using Gelucire 50/13. Pharm Res. 2005;22:1727–34.
Sarode AL, Malekar SA, Cote C, Worthen DR. Hydroxypropyl cellulose stabilizes amorphous solid dispersions of the poorly water soluble drug felodipine. Carbohydr Polym Elsevier Ltd. 2014;112:512–9. Available from: https://doi.org/10.1016/j.carbpol.2014.06.039.
Konno H, Taylor LS. Influence of different polymers on the crystallization tendency of molecularly dispersed amorphous felodipine. J Pharm Sci. 2006;95:2692–705.
Liu J, Cao F, Zhang C, Ping Q. Use of polymer combinations in the preparation of solid dispersions of a thermally unstable drug by hot-melt extrusion. Acta Pharm Sin B. 2013;3:263–72. http://www.sciencedirect.com/science/article/pii/S2211383513000646.
Aramwit P. Effectiveness of inflammatory cytokines induced by sericin compared to sericin in combination with silver sulfadiazine cream on wound healing. Wounds. 2009;21:198–206.
Aramwit P, Keongamaroon O, Siritientong T, Bang N, Supasyndh O. Sericin cream reduces pruritus in hemodialysis patients: a randomized, double-blind, placebo-controlled experimental study. BMC Nephrol. 2012;13:119. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3472272&tool=pmcentrez&rendertype=abstract.
Kitisin T, Maneekan P, Luplertlop N. In-vitro characterization of silk sericin as an anti-aging agent. J Agric Sci. 2013;5:54–63.
Zhaorigetu S, Yanaka N, Sasaki M, Watanabe H, Kato N. Inhibitory effects of silk protein, sericin on UVB-induced acute damage and tumor promotion by reducing oxidative stress in the skin of hairless mouse. J Photochem Photobiol B Biol. 2003;71:11–7.
Takasu Y, Yamada H, Tsubouchi K. Isolation of three main sericin components from the cocoon of the silkworm, Bombyx mori. Biosci Biotechnol Biochem. 2002;66:2715–8.
Tao W, Li M, Xie R. Preparation and structure of porous silk sericin materials. Macromol Mater Eng. 2005;290:188–94.
Aramwit P, Siritientong T, Srichana T. Potential applications of silk sericin, a natural protein from textile industry by-products. Waste Manag Res. 2012;30:217–24. http://www.researchgate.net/publication/51113185_Potential_applications_of_silk_sericin_a_natural_protein_from_textile_industry_by-products.
Morikawa M, Kimura T, Murakami M, Katayama K, Terada S, Yamaguchi A. Rat islet culture in serum-free medium containing silk protein sericin. J Hepato-Biliary-Pancreat Surg. 2009;16:223–8.
Terada S, Nishimura T, Sasaki M, Yamada H, Miki M. Sericin, a protein derived from silkworms, accelerates the proliferation of several mammalian cell lines including a hybridoma. Cytotechnology. 2003;40:3–12.
Tsujimoto K, Takagi H, Takahashi M, Yamada H, Nakamori S, Tagaki H, et al. Cryoprotective effect of the serine-rich repetitive sequence in silk protein sericin. J Biochem. 2001;986:979–86.
Salunkhe NH, Jadhav NR, More HN, Jadhav AD. Screening of drug-sericin solid dispersions for improved solubility and dissolution. Int J Biol Macromol Elsevier BV. 2018;107:1683–91. Available from. https://doi.org/10.1016/j.ijbiomac.2017.10.035.
Zhang YQ. Applications of natural silk protein sericin in biomaterials. Biotechnol Adv. 2002;20:91–100.
Rawlinson CF, Williams AC, Timmins P, Grimsey I. Polymer-mediated disruption of drug crystallinity. Int J Pharm. 2007;336:42–8.
Deodware SA, Sathe DJ, Choudhari PB, Lokhande TN, Gaikwad SH. Development and molecular modeling of Co(II), Ni(II) and Cu(II) complexes as high acting anti breast cancer agents. Arab J Chem The Authors. 2017;10:262–72. Available from: https://doi.org/10.1016/j.arabjc.2016.09.024.
Abhale YK, Shinde AD, Deshmukh KK, Nawale L, Sarkar D, Choudhari PB, et al. Synthesis, antimycobacterial screening and molecular docking studies of 4-aryl-4′-methyl-2′-aryl-2,5′-bisthiazole derivatives. Med Chem Res Springer US. 2017;26:1–11. Available from: https://doi.org/10.1007/s00044-017-1988-5.
Patravale AA, Gore AH, Kolekar GB, Deshmukh MB, Choudhari PB, Bhatia MS, et al. Synthesis, biological evaluation and molecular docking studies of some novel indenospiro derivatives as anticancer agents. J Taiwan Inst Chem Eng Elsevier BV. 2016;68:105–18. Available from: https://doi.org/10.1016/j.jtice.2016.09.034.
Shibata YFM, Kokudai M, Noda S, Okada H, Kondoh M, Watanabe Y. Effect of characteristics of compounds on maintenance of an amorphous state in solid dispersion with crospovidone. J Pharm Sci. 2007;96:1537–47.
Savolainen M, Kogermann K, Heinz A, Aaltonen J, Peltonen L, Strachan C, et al. Better understanding of dissolution behaviour of amorphous drugs by in situ solid-state analysis using Raman spectroscopy. Eur J Pharm Biopharm Elsevier BV. 2009;71:71–9. Available from: https://doi.org/10.1016/j.ejpb.2008.06.001.
Ahmed MO, Al-Badr AA. Lornoxicam. 1st ed. profiles drug Subst. Excipients Relat. Methodol. Elsevier Inc.; 2011. Available from: https://doi.org/10.1016/B978-0-12-387667-6.00006-3.
Ozaki S, Minamisono T, Yamashita T, Kato T, Kushida I. Supersaturation–nucleation behavior of poorly soluble drugs and its impact on the oral absorption of drugs in thermodynamically high-energy forms. J Pharm Sci. 2012;101:214–22.
Ozaki S, Kushida I, Yamashita T, Hasebe T, Shirai O, Kano K. Evaluation of drug supersaturation by thermodynamic and kinetic approaches for the prediction of oral absorbability in amorphous pharmaceuticals. J Pharm Sci. 2012;101:4220–30.
Ozaki S, Kushida I, Yamashita T, Hasebe T, Shirai O, Kano K. Inhibition of crystal nucleation and growth by water-soluble polymers and its impact on the supersaturation profiles of amorphous drugs. J Pharm Sci. 2013;102:2273–81.
Saboo S, Mugheirbi NA, Zemlyanov DY, Kestur US, Taylor LS. Congruent release of drug and polymer: a “sweet spot” in the dissolution of amorphous solid dispersions. J Control Release Elsevier BV. 2019;298:68–82. Available from. https://doi.org/10.1016/j.jconrel.2019.01.039.
Sethia S, Squillante E. Solid dispersion of carbamazepine in PVP K30 by conventional solvent evaporation and supercritical methods. Int J Pharm. 2004;272:1–10.
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Salunkhe, N., Jadhav, N., More, H. et al. Sericin Inhibits Devitrification of Amorphous Drugs. AAPS PharmSciTech 20, 285 (2019). https://doi.org/10.1208/s12249-019-1475-z
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DOI: https://doi.org/10.1208/s12249-019-1475-z