Advertisement

AAPS PharmSciTech

, 20:95 | Cite as

Enhancement of Transdermal Delivery of Haloperidol via Spanlastic Dispersions: Entrapment Efficiency vs. Particle Size

  • Abdurrahman M. FahmyEmail author
  • Doaa Ahmed El-Setouhy
  • Basant A. Habib
  • Saadia A. Tayel
Research Article
  • 23 Downloads

ABSTRACT

Haloperidol (Hal) is a well-known typical antipsychotic. Hepatic first pass metabolism leads to its limited oral bioavailability. This study aimed at enhancing transdermal delivery of Hal via spanlastic formulae. Hal-loaded spanlastics of Span®60 and an edge activator (EA) were successfully prepared by ethanol injection method according to a 31.41 full factorial design. In this design, independent variables were X1, EA type, and X2, Span®60 to EA ratio. Y1, percentage entrapment efficiency (EE%); Y2, particle size (PS); Y3, deformability index (DI); and Y4, percentage drug released after 4h (Q4h), were chosen as dependent variables. The Fourier-transform infrared spectral analysis showed no considerable chemical interaction between Hal and the used excipients. Both factors affected significantly all the responses except DI. Desirability of each prepared formula was calculated based on maximizing EE% and Q4h and minimizing PS. Formula F6, with X1, Tween®80, and X2, 8:2, had the highest desirability value followed by F7, with X1, Tween®80, and X2, 6:4, and both were chosen as selected formulae (SF) for further investigation. F6 (having more entrapped Hal), F7 (of smaller PS), and Hal solution in propylene glycol were subjected to ex vivo permeation test through newborn rat skin. Both formulae showed marked enhancement in drug permeation compared with drug solution. The significantly higher Q36h and J36h of F7 from F6 may indicate that the smaller particle size aided more than higher entrapment in achieving a higher permeation for Hal of 3.5±0.2μg/cm2.h. These results are promising for further investigation of this formula.

KEY WORDS

haloperidol spanlastics factorial design transdermal ex vivo permeation 

Notes

References

  1. 1.
    Derendorf H, Mutschler E. Drug actions: basic principles and therapeutic aspects: CRC press; 1995.Google Scholar
  2. 2.
    Dold M, Samara MT, Li C, Tardy M, Leucht S. Haloperidol versus first-generation antipsychotics for the treatment of schizophrenia and other psychotic disorders. Cochrane Database Syst Rev. 2015;2015(1):CD009831.  https://doi.org/10.1002/14651858.CD009831.pub2.CrossRefGoogle Scholar
  3. 3.
    El-Setouhy DA, Ibrahim A, Amin MM, Khowessah OM, Elzanfaly ES. Intranasal haloperidol-loaded miniemulsions for brain targeting: evaluation of locomotor suppression and in-vivo biodistribution. Eur J Pharm Sci. 2016;92:244–54.  https://doi.org/10.1016/j.ejps.2016.05.002.CrossRefPubMedGoogle Scholar
  4. 4.
    Elgorashi AS, Heard CM, Niazy EM, Noureldin OH, Pugh WJ. Transdermal delivery enhancement of haloperidol from gel formulations by 1, 8-cineole. J Pharm Pharmacol. 2008;60(6):689–92.  https://doi.org/10.1211/jpp.60.6.0002.CrossRefPubMedGoogle Scholar
  5. 5.
    Volavka J, Cooper T, Czobor P, Bitter I, Meisner M, Laska E, et al. Haloperidol blood levels and clinical effects. Arch Gen Psychiatry. 1992;49(5):354–61.  https://doi.org/10.1001/archpsyc.1992.01820050018002.CrossRefPubMedGoogle Scholar
  6. 6.
    Potts RO, Guy RH. Predicting skin permeability. Pharm Res. 1992;9(5):663–9.  https://doi.org/10.1023/A:1015810312465.CrossRefPubMedGoogle Scholar
  7. 7.
    Vaddi H, Ho P, Chan S. Terpenes in propylene glycol as skin-penetration enhancers: permeation and partition of haloperidol, fourier transform infrared spectroscopy, and differential scanning calorimetry. J Pharm Sci. 2002;91(7):1639–51.  https://doi.org/10.1002/jps.10160.CrossRefPubMedGoogle Scholar
  8. 8.
    Azarbayjani AF, Tan EH, Chan YW, Chan SY. Transdermal delivery of haloperidol by proniosomal formulations with non-ionic surfactants. Biol Pharm Bull. 2009;32(8):1453–8.  https://doi.org/10.1248/bpb.32.1453.CrossRefPubMedGoogle Scholar
  9. 9.
    Kang L, Liu X, Sawant P, Ho P, Chan Y, Chan S. SMGA gels for the skin permeation of haloperidol. J Control Release. 2005;106(1):88–98.  https://doi.org/10.1016/j.jconrel.2005.04.017.CrossRefPubMedGoogle Scholar
  10. 10.
    Lim PFC, Liu XY, Kang L, Ho PCL, Chan YW, Chan SY. Limonene GP1/PG organogel as a vehicle in transdermal delivery of haloperidol. Int J Pharm. 2006;311(1):157–64.  https://doi.org/10.1016/j.ijpharm.2005.12.042.CrossRefPubMedGoogle Scholar
  11. 11.
    Alvarez-Figueroa M, Araya-Silva I, Díaz-Tobar C. Iontophoretic transdermal delivery of haloperidol. Pharm Dev Technol. 2006;11(3):371–5.  https://doi.org/10.1080/10837450600770148.CrossRefPubMedGoogle Scholar
  12. 12.
    Balakrishnan P, Shanmugam S, Lee WS, Lee WM, Kim JO, Oh DH, et al. Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery. Int J Pharm. 2009;377(1):1–8.  https://doi.org/10.1016/j.ijpharm.2009.04.020.CrossRefPubMedGoogle Scholar
  13. 13.
    Kakkar S, Pal Kaur I. A novel nanovesicular carrier system to deliver drug topically. Pharm Dev Technol. 2013;18(3):673–85.  https://doi.org/10.3109/10837450.2012.685655.CrossRefPubMedGoogle Scholar
  14. 14.
    Kakkar S, Kaur IP. Spanlastics—a novel nanovesicular carrier system for ocular delivery. Int J Pharm. 2011;413(1):202–10.  https://doi.org/10.1016/j.ijpharm.2011.04.027.CrossRefPubMedGoogle Scholar
  15. 15.
    Tayel SA, El-Nabarawi MA, Tadros MI, Abd-Elsalam WH. Duodenum-triggered delivery of pravastatin sodium via enteric surface-coated nanovesicular spanlastic dispersions: development, characterization and pharmacokinetic assessments. Int J Pharm. 2015;483(1):77–88.  https://doi.org/10.1016/j.ijpharm.2015.02.012.CrossRefPubMedGoogle Scholar
  16. 16.
    Tenjarla S, Puranajoti P, Kasina R, Mandal T. Preparation, characterization, and evaluation of miconazole–cyclodextrin complexes for improved oral and topical delivery. J Pharm Sci. 1998;87(4):425–9.  https://doi.org/10.1021/js970361l.CrossRefPubMedGoogle Scholar
  17. 17.
    Abdelbary G. Ocular ciprofloxacin hydrochloride mucoadhesive chitosan-coated liposomes. Pharm Dev Technol. 2011;16(1):44–56.  https://doi.org/10.3109/10837450903479988.CrossRefPubMedGoogle Scholar
  18. 18.
    Maestrelli F, González-Rodríguez ML, Rabasco AM, Mura P. Preparation and characterisation of liposomes encapsulating ketoprofen–cyclodextrin complexes for transdermal drug delivery. Int J Pharm. 2005;298(1):55–67.  https://doi.org/10.1016/j.ijpharm.2005.03.033.CrossRefPubMedGoogle Scholar
  19. 19.
    Aburahma MH, Abdelbary GA. Novel diphenyl dimethyl bicarboxylate provesicular powders with enhanced hepatocurative activity: preparation, optimization, in vitro/in vivo evaluation. Int J Pharm. 2012;422(1):139–50.  https://doi.org/10.1016/j.ijpharm.2011.10.043.CrossRefPubMedGoogle Scholar
  20. 20.
    Xu H, He L, Nie S, Guan J, Zhang X, Yang X, et al. Optimized preparation of vinpocetine proliposomes by a novel method and in vivo evaluation of its pharmacokinetics in New Zealand rabbits. J Control Release. 2009;140(1):61–8.  https://doi.org/10.1016/j.jconrel.2009.07.014.CrossRefPubMedGoogle Scholar
  21. 21.
    Scognamiglio I, De Stefano D, Campani V, Mayol L, Carnuccio R, Fabbrocini G, et al. Nanocarriers for topical administration of resveratrol: a comparative study. Int J Pharm. 2013;440(2):179–87.  https://doi.org/10.1016/j.ijpharm.2012.08.009.CrossRefPubMedGoogle Scholar
  22. 22.
    El Zaafarany GM, Awad GA, Holayel SM, Mortada ND. Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery. Int J Pharm. 2010;397(1):164–72.  https://doi.org/10.1016/j.ijpharm.2010.06.034.CrossRefPubMedGoogle Scholar
  23. 23.
    Lei W, Yu C, Lin H, Zhou X. Development of tacrolimus-loaded transfersomes for deeper skin penetration enhancement and therapeutic effect improvement in vivo. Asian J Pharm. 2013;8(6):336–45.  https://doi.org/10.1016/j.ajps.2013.09.005.CrossRefGoogle Scholar
  24. 24.
    Gupta PN, Mishra V, Rawat A, Dubey P, Mahor S, Jain S, et al. Non-invasive vaccine delivery in transfersomes, niosomes and liposomes: a comparative study. Int J Pharm. 2005;293(1–2):73–82.  https://doi.org/10.1016/j.ijpharm.2004.12.022.CrossRefPubMedGoogle Scholar
  25. 25.
    Shamma RN, Elsayed I. Transfersomal lyophilized gel of buspirone HCl: formulation, evaluation and statistical optimization. J Liposome Res. 2013;23(3):244–54.  https://doi.org/10.3109/08982104.2013.801489.CrossRefPubMedGoogle Scholar
  26. 26.
    Kumar R, Singh B, Bakshi G, Katare OP. Development of liposomal systems of finasteride for topical applications: design, characterization, and in vitro evaluation. Pharm Dev Technol. 2007;12(6):591–601.  https://doi.org/10.1080/10837450701481181.CrossRefPubMedGoogle Scholar
  27. 27.
    Al-mahallawi AM, Abdelbary AA, Aburahma MH. Investigating the potential of employing bilosomes as a novel vesicular carrier for transdermal delivery of tenoxicam. Int J Pharm. 2015;485(1):329–40.  https://doi.org/10.1016/j.ijpharm.2015.03.033.CrossRefPubMedGoogle Scholar
  28. 28.
    Vaddi H, Wang L, Ho P, Chan S. Effect of some enhancers on the permeation of haloperidol through rat skin in vitro. Int J Pharm. 2001;212(2):247–55.  https://doi.org/10.1016/S0378-5173(00)00616-5.CrossRefPubMedGoogle Scholar
  29. 29.
    Fahmy AM, El-Setouhy DA, Ibrahim AB, Habib BA, Tayel SA, Bayoumi NA. Penetration enhancer-containing spanlastics (PECSs) for transdermal delivery of haloperidol: in vitro characterization, ex vivo permeation and in vivo biodistribution studies. Drug Deliv. 2018;25(1):12–22.  https://doi.org/10.1080/10717544.2017.1410262.CrossRefPubMedGoogle Scholar
  30. 30.
    Basalious EB, Shawky N, Badr-Eldin SM. SNEDDS containing bioenhancers for improvement of dissolution and oral absorption of lacidipine. I: development and optimization. Int J Pharm. 2010;391(1):203–11.  https://doi.org/10.1016/j.ijpharm.2010.03.008.CrossRefPubMedGoogle Scholar
  31. 31.
    Loukas YL, Vraka V, Gregoriadis G. Novel non-acidic formulations of haloperidol complexed with β-cyclodextrin derivatives. J Pharm Biomed Anal. 1997;16(2):263–8.  https://doi.org/10.1016/S0731-7085(97)00029-0.CrossRefPubMedGoogle Scholar
  32. 32.
    Rowe RC, Sheskey PJ, Quinn M. Handbook of pharmaceutical excipients E version. 7th ed. London: Pharmaceutical Press and American Pharmacists Association; 2012.Google Scholar
  33. 33.
    Trotta M, Peira E, Debernardi F, Gallarate M. Elastic liposomes for skin delivery of dipotassium glycyrrhizinate. Int J Pharm. 2002;241(2):319–27.  https://doi.org/10.1016/S0378-5173(02)00266-1.CrossRefPubMedGoogle Scholar
  34. 34.
    Hao Y, Zhao F, Li N, Yang Y, Li KA. Studies on a high encapsulation of colchicine by a niosome system. Int J Pharm. 2002;244(1):73–80.  https://doi.org/10.1016/S0378-5173(02)00301-0.CrossRefPubMedGoogle Scholar
  35. 35.
    Abdelrahman FE, Elsayed I, Gad MK, Elshafeey AH, Mohamed MI. Response surface optimization, ex vivo and in vivo investigation of nasal spanlastics for bioavailability enhancement and brain targeting of risperidone. Int J Pharm. 2017;530(1–2):1–11.  https://doi.org/10.1016/j.ijpharm.2017.07.050.CrossRefPubMedGoogle Scholar
  36. 36.
    Viswanathan NB, Thomas P, Pandit J, Kulkarni M, Mashelkar R. Preparation of non-porous microspheres with high entrapment efficiency of proteins by a (water-in-oil)-in-oil emulsion technique. J Control Release. 1999;58(1):9–20.  https://doi.org/10.1016/S0168-3659(98)00140-0.CrossRefPubMedGoogle Scholar
  37. 37.
    Abdelbary G, El-gendy N. Niosome-encapsulated gentamicin for ophthalmic controlled delivery. AAPS PharmSciTech. 2008;9(3):740–7.  https://doi.org/10.1208/s12249-008-9105-1.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Wacker M. Nanocarriers for intravenous injection—the long hard road to the market. Int J Pharm. 2013;457(1):50–62.  https://doi.org/10.1016/j.ijpharm.2013.08.079.CrossRefPubMedGoogle Scholar
  39. 39.
    Rodríguez-García R, Mell M, López-Montero I, Netzel J, Hellweg T, Monroy F. Polymersomes: smart vesicles of tunable rigidity and permeability. Soft Matter. 2011;7(4):1532–42.  https://doi.org/10.1039/C0SM00823K.CrossRefGoogle Scholar
  40. 40.
    Salama HA, Mahmoud AA, Kamel AO, Abdel Hady M, Awad GA. Brain delivery of olanzapine by intranasal administration of transfersomal vesicles. J Liposome Res. 2012;22(4):336–45.  https://doi.org/10.3109/08982104.2012.700460.CrossRefPubMedGoogle Scholar
  41. 41.
    Duangjit S, Opanasopit P, Rojanarata T, Ngawhirunpat T. Characterization and in vitro skin permeation of meloxicam-loaded liposomes versus transfersomes. J Drug Deliv. 2010;2011:1–9.  https://doi.org/10.1155/2011/418316.CrossRefGoogle Scholar
  42. 42.
    Fang J-Y, Yu S-Y, Wu P-C, Huang Y-B, Tsai Y-H. In vitro skin permeation of estradiol from various proniosome formulations. Int J Pharm. 2001;215(1):91–9.  https://doi.org/10.1016/S0378-5173(00)00669-4.CrossRefPubMedGoogle Scholar
  43. 43.
    Gupta PN, Mishra V, Singh P, Rawat A, Dubey P, Mahor S, et al. Tetanus toxoid-loaded transfersomes for topical immunization. J Pharm Pharmacol. 2005;57(3):295–301.  https://doi.org/10.1211/0022357055515.CrossRefPubMedGoogle Scholar
  44. 44.
    Basha M, Abd El-Alim SH, Shamma RN, Awad GE. Design and optimization of surfactant-based nanovesicles for ocular delivery of Clotrimazole. J Liposome Res. 2013;23(3):203–10.  https://doi.org/10.3109/08982104.2013.788025.CrossRefPubMedGoogle Scholar
  45. 45.
    van den Bergh BA, Wertz PW, Junginger HE, Bouwstra JA. Elasticity of vesicles assessed by electron spin resonance, electron microscopy and extrusion measurements. Int J Pharm. 2001;217(1):13–24.  https://doi.org/10.1016/S0378-5173(01)00576-2.CrossRefPubMedGoogle Scholar
  46. 46.
    Al-mahallawi AM, Khowessah OM, Shoukri RA. Nano-transfersomal ciprofloxacin loaded vesicles for non-invasive trans-tympanic ototopical delivery: in-vitro optimization, ex-vivo permeation studies, and in-vivo assessment. Int J Pharm. 2014;472(1):304–14.  https://doi.org/10.1016/j.ijpharm.2014.06.041.CrossRefPubMedGoogle Scholar
  47. 47.
    Dora CP, Singh SK, Kumar S, Datusalia AK, Deep A. Development and characterization of nanoparticles of glibenclamide by solvent displacement method. Acta Pol Pharm. 2010;67(3):283–90.PubMedGoogle Scholar
  48. 48.
    Ghorab DM, Amin MM, Khowessah OM, Tadros MI. Colon-targeted celecoxib-loaded Eudragit® S100-coated poly-ϵ-caprolactone microparticles: preparation, characterization and in vivo evaluation in rats. Drug Deliv. 2011;18(7):523–35.  https://doi.org/10.3109/10717544.2011.595841.CrossRefPubMedGoogle Scholar
  49. 49.
    Junyaprasert VB, Singhsa P, Suksiriworapong J, Chantasart D. Physicochemical properties and skin permeation of Span 60/Tween 60 niosomes of ellagic acid. Int J Pharm. 2012;423(2):303–11.  https://doi.org/10.1016/j.ijpharm.2011.11.032.CrossRefPubMedGoogle Scholar
  50. 50.
    Salama HA, Mahmoud AA, Kamel AO, Hady MA, Awad GA. Phospholipid based colloidal poloxamer–nanocubic vesicles for brain targeting via the nasal route. Colloids Surf B Biointerfaces. 2012;100:146–54.  https://doi.org/10.1016/j.colsurfb.2012.05.010.CrossRefPubMedGoogle Scholar
  51. 51.
    Marks R, Dawber R. Skin surface biopsy: an improved technique for the examination of the horny layer. Br J Dermatol. 1971;84(2):117–23.  https://doi.org/10.1111/j.1365-2133.1971.tb06853.x.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyCairo UniversityCairoEgypt

Personalised recommendations