International Journal of Drug Delivery Technology
Volume 14, Issue 4

Utilizing Intranasal Drug Delivery Systems for Novel Antipsychotics Drug Development

Ainurofiq A*, Priyanto F A P, Suryadi B T, Pamungkas Y K

Department of Pharmacy, Sebelas Maret University, Ir. Sutami 36A, Surakarta City, 57126 Indonesia 

Received: 28th Sep, 2024; Revised: 16th Nov, 2024; Accepted: 27th Nov, 2024; Available Online: 25th Dec, 2024 

ABSTRACT

Psychotic illnesses are significant symptoms of various mental disorders, including psychotic depression, bipolar disorder and schizophrenia. The high incidence of psychotic illness can be attributed to several factors, including low patient compliance stemming from limitations in antipsychotic treatments. Antipsychotics are pharmacological therapies used to manage psychotic disorders, addressing acute episodes and preventing relapses. However, these drugs often exhibit limited physicochemical properties, suboptimal pharmacokinetic profiles, low bioavailability, and insufficient solubility, which hinder their ability go through the blood-brain barrier (BBB). The traditional dosage forms and routes of administration, primarily oral and injectable also pose further challenges. The intranasal delivery system offers a promising alternative to overcome these limitations by facilitating drug administration through the nasal cavity, allowing for quick uptake into the bloodstream while circumventing enzymatic degradation and first-pass metabolism associated with oral routes. The intranasal route can achieve significant drug concentrations in the brain without interference from the BBB, increasing bioavailability and enabling a rapid onset of pharmacological effects at lower doses and frequencies than oral medications. Nonetheless, anatomical, physiological, histological challenges as well as the fundamental processes involved in drug uptake via the nasal epithelium complicate systemic and brain distribution. The effectiveness of intranasal antipsychotic formulations can be improved through different drug delivery systems (DDS) such as nanoparticles, liposomes, nanogels, and other nanocarriers that help transport the drugs from the nasal cavity to the brain.

Keywords: antipsychotics, formulation development, intranasal, drug delivery system

How to cite this article: Ainurofiq A, Priyanto F A P, Suryadi B T, Pamungkas Y K. Utilizing Intranasal Drug Delivery Systems for Novel Antipsychotics Drug Development. International Journal of Drug Delivery Technology. 2024;14(4):2091-101. doi: 10.25258/ijddt.14.4.21

REFERENCES

  1. Waller H, Freeman D, Jolley S, Dunn G, Garety P. Targeting reasoning biases in delusions: A pilot study of the Maudsley Review Training Programme for individuals with persistent, high conviction delusions. Journal of Behavior Therapy and Experimental Psychiatry. 2011;42(3):414-421.
  2. Calabrese J, Al Khalili Y. Psychosis. In: StatPearls. StatPearls Publishing; 2023.
  3. Bergonzi MC, Bilia AR, Landucci E. Applications of innovative technologies to the delivery of antipsychotics. Drug Discovery Today. 2022;27(2):401-421.
  4. DiPiro JT, ed. Pharmacotherapy: A Pathophysiologic Approach. Eleventh edition. McGraw Hill Medical;
  5. Stroup TS, Gray N. Management of common adverse effects of antipsychotic World Psychiatry. 2018;17(3):341-356.
  6. Ainurofiq A, Ismaya L. Pharmacokinetic Drug-Drug Interactions: A Systematic Review of the Cytochrome P450 (CYP) Isoenzyme 3A4. Research Journal of Pharmacy and Technology. 2023;16(6):3016-3024.
  7. Biddlestone-Thorpe L, Marchi N, Guo K, et al. Nanomaterial-mediated CNS delivery of diagnostic and therapeutic agents. Advanced Drug Delivery Reviews. 2012;64(7):605-613.
  8. Lochhead JJ, Thorne RG. Intranasal delivery of biologics to the central nervous Advanced Drug Delivery Reviews. 2012;64(7):614-628.
  9. Pardridge WM. The blood-brain barrier: Bottleneck in brain drug development. Neurotherapeutics. 2005;2(1):3-14.
  10. Grassin-Delyle S, Buenestado A, Naline E, et al. Intranasal drug delivery: An efficient and non-invasive route for systemic administration. Pharmacology & Therapeutics. 2012;134(3):366-379.
  11. Bitter C, Suter-Zimmermann K, Surber C. Nasal Drug Delivery in In: Surber C, Elsner P, Farage MA, eds. Current Problems in Dermatology. Vol 40. S. Karger AG; 2011:20-35.
  12. Markowicz-Piasecka M, Darłak P, Markiewicz A, et Current approaches to facilitate improved drug delivery to the central nervous system. European Journal of Pharmaceutics and Biopharmaceutics. 2022;181:249- 262.
  13. Brewster PR, Mohammad Ishraq Bari S, Walker GM, Werfel TA. Current and future directions of drug delivery for the treatment of mental Advanced Drug Delivery Reviews. 2023;197:114824.
  14. Katare YK, Piazza JE, Bhandari J, et al. Intranasal delivery of antipsychotic drugs. Schizophrenia Research. 2017;184:2-13.
  15. Haumann R, Videira JC, Kaspers GJL, Van Vuurden DG, Hulleman E. Overview of Current Drug Delivery Methods Across the Blood–Brain Barrier for the Treatment of Primary Brain Tumors. CNS Drugs. 2020;34(11):1121-1131.
  16. Vitore JG, Bharathi K, Salave S, et al. Intranasal transmucosal drug delivery: An alternative approach to the parenteral route for medical Journal of Drug Delivery Science and Technology. 2023;83:104421.
  17. Shrestha P, Fariba KA, Abdijadid S. Paroxetine. In: StatPearls. StatPearls Publishing; 2023.
  18. Sharbaf Shoar N, Fariba KA, Padhy Citalopram. In: StatPearls. StatPearls Publishing; 2023.
  19. Ghiasi N, Bhansali RK, Marwaha R. Lorazepam. In: StatPearls. StatPearls Publishing; 2023.
  20. Dhaliwal JS, Rosani A, Saadabadi A. Diazepam. In: StatPearls. StatPearls Publishing; 2023.
  21. El-Tokhy FS, Abdel-Mottaleb MMA, El-Ghany EA, Geneidi Transdermal delivery of second-generation antipsychotics for management of schizophrenia; disease overview, conventional and nanobased drug delivery systems. Journal of Drug Delivery Science and Technology. 2021;61:102104.
  22. Narala A, Veerabrahma K. Preparation, Characterization and Evaluation of Quetiapine Fumarate Solid Lipid Nanoparticles to Improve the Oral Bioavailability. Journal of 2013;2013:1- 7.
  23. Leung JG, Nelson S, Cunningham JL, et al. A Single- Dose Crossover Pharmacokinetic Comparison Study of Oral, Rectal and Topical Quetiapine in Healthy Clin Pharmacokinet. 2016;55(8):971-976.
  24. Eisa AM, El-Megrab NA, El-Nahas HM. Formulation and evaluation of fast dissolving tablets of haloperidol solid dispersion. Saudi Pharmaceutical Journal. 2022;30(11):1589-1602.
  25. Pardeshi CV, Dhangar RN, Jagatap VR, Sonawane New cationic neuronanoemulsion-laden Eulophia herbacea mucilage based mucoadhesive hydrogel for intranasal delivery of chlorpromazine. Materials Technology. 2021;36(4):189-202.
  26. Alves R, Reis TVDS, Silva LCCD, Storpírtis S, Mercuri LP, Matos JDR. Thermal behavior and decomposition kinetics of rifampicin polymorphs under isothermal and non-isothermal conditions. Braz J Pharm Sci. 2010;46(2):343-351.
  27. Arciniegas DB. Psychosis: CONTINUUM: Lifelong Learning in Neurology. 2015;21:715-736.
  28. Sorter MT, Vogel DA. Psychotic Disorders. In: Adolescent Medicine. Elsevier; 2008:291-296.
  29. Patel KR, Cherian J, Gohil K, Atkinson D. Schizophrenia: overview and treatment options. P T. 2014;39(9):638-645.
  30. Corrie L, Gulati M, Awasthi A, et al. Polysaccharide, fecal microbiota, and curcumin-based novel oral colon- targeted solid self-nanoemulsifying delivery system: formulation, characterization, and in-vitro anticancer evaluation. Materials Today Chemistry. 2022;26:101165.
  31. Correll CU, Schooler NR. Negative Symptoms in Schizophrenia: A Review and Clinical Guide for Recognition, Assessment, and Treatment. NDT. 2020;Volume 16:519-534.
  32. Katzung BG, ed. Basic & Clinical Pharmacology. 9th ed. Lange Medical Books/McGraw Hill; 2004.
  33. Katzung BG, ed. Basic & Clinical Pharmacology. Fourteenth edition. McGraw-Hill Education; 2018.
  34. American Psychiatric Association, ed. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th American Psychiatric Association; 2013.
  35. Chakrabarti S, Singh Psychotic symptoms in bipolar disorder and their impact on the illness: A systematic review. WJP. 2022;12(9):1204-1232.
  36. Rothschild AJ. Challenges in the treatment of major depressive disorder with psychotic features. Schizophr Bull. 2013;39(4):787-796.
  37. Lakshmikuttyamma A, Hajjar E, Henley C, Lungen Antipsychotic agents. In: Side Effects of Drugs Annual. Vol 44. Elsevier; 2022:7-16.
  38. Bishara D, Taylor D. Upcoming Agents for the Treatment of Schizophrenia: Mechanism of Action, Efficacy and Tolerability. Drugs. 2008;68(16):2269-
  39. Abi-Dargham A, Laruelle M. Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies. Eur psychiatr. 2005;20(1):15-27.
  40. Willner K, Vasan S, Abdijadid S. Atypical Antipsychotic Agents. In: StatPearls. StatPearls Publishing;
  41. Malhi GS, Tanious M, Das P, Berk The science and practice of lithium therapy. Aust N Z J Psychiatry. 2012;46(3):192-211.
  42. Yatham LN, Kennedy SH, Schaffer A, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2009. Bipolar Disorders. 2009;11(3):225-255.
  43. Pacchiarotti I, Bond DJ, Baldessarini RJ, et al. The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders. AJP. 2013;170(11):1249-1262.
  44. Cascade EF, Reites J, Kalali AH, Ghaemi N. Antidepressants in bipolar disorder. Psychiatry (Edgmont). 2007;4(3):56-58.
  45. Baldessarini RJ, Leahy L, Arcona S, Gause D, Zhang W, Hennen J. Patterns of Psychotropic Drug Prescription for U.S. Patients With Diagnoses of Bipolar Disorders. PS. 2007;58(1):85-91.
  46. Ferreira MD, Duarte J, Veiga F, Paiva-Santos AC, Pires PC. Nanosystems for Brain Targeting of Antipsychotic Drugs: An Update on the Most Promising Nanocarriers for Increased Bioavailability and Therapeutic Efficacy. Pharmaceutics. 2023;15(2):678.
  47. Majcher MJ, Babar A, Lofts A, et al. In situ-gelling starch nanoparticle (SNP)/O-carboxymethyl chitosan (CMCh) nanoparticle network hydrogels for the intranasal delivery of an antipsychotic peptide. Journal of Controlled Release. 2021;330:738-752.
  48. Bourganis V, Kammona O, Alexopoulos A, Kiparissides C. Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics. European Journal of Pharmaceutics and Biopharmaceutics. 2018;128:337-362.
  49. Montegiove N, Calzoni E, Emiliani C, Cesaretti A. Biopolymer Nanoparticles for Nose-to-Brain Drug Delivery: A New Promising Approach for the Treatment of Neurological Diseases. JFB. 2022;13(3):125.
  50. Henriques P, Fortuna A, Doktorovová S. Spray dried powders for nasal delivery: Process and formulationconsiderations. European Journal of Pharmaceutics and Biopharmaceutics. 2022;176:1-20.
  51. Goel H, Kalra V, Verma SK, Dubey SK, Tiwary AK. Convolutions in the rendition of nose to brain therapeutics from bench to bedside: Feats & fallacies. Journal of Controlled Release. 2022;341:782-811.
  52. Shrewsbury SB, Hocevar-Trnka J, Satterly KH, Craig KL, Lickliter JD, Hoekman J. The SNAP 101 Double- Blind, Placebo/Active-Controlled, Safety, Pharmacokinetic, and Pharmacodynamic Study of INP105 (Nasal Olanzapine) in Healthy Adults. J Clin Psychiatry. 2020;81(4).
  53. Kooij KL, Luijendijk MCM, Drost L, Platenburg G, Van Elburg A, Adan Intranasal administration of olanzapine has beneficial outcome in a rat activity- based anorexia model.             European Neuropsychopharmacology. 2023;71:65-74.
  54. Thakkar H, Vaghela D, Patel BP. Brain targeted intranasal in-situ gelling spray of paroxetine: Formulation, characterization and in-vivo evaluation". Journal of Drug Delivery Science and Technology. 2021;62:102317.
  55. Karavasili C, Fatouros Smart materials: in situ gel- forming systems for nasal delivery. Drug Discovery Today. 2016;21(1):157-166.
  56. Ezike TC, Okpala US, Onoja UL, et al. Advances in drug delivery systems, challenges and future Heliyon. 2023;9(6):e17488.
  57. Sherafudeen SP, Vasantha PV. Development and evaluation of in situ nasal gel formulations of Res Pharm Sci. 2015;10(6):466-476.
  58. Ainurofiq A, Sari APF, Mardhiyah A, et Chitosan as floating-mucoadhesive polymers in gastroretentive drug delivery. Science, Engineering and Health Studies. Published online December 31, 2023:23010002-23010002.
  59. Zhou C hong, Xue S shan, Xue F, et al. The impact of quetiapine on the brain lipidome in a cuprizone-induced mouse model of schizophrenia. Biomedicine & Pharmacotherapy. 2020;131:110707.
  60. Gadhave D, Quadros M, Ugale AR, Goyal M, Gupta A Nanoemulgel for Nose-to-Brain delivery of Quetiapine – QbD-Enabled formulation development & in-vitro characterization. International Journal of Pharmaceutics. 2023;648:123566.
  61. Al-Mumtahanah A, Banowati NA, Dewi TAS, Nurbaiti FA, Rachmadani SA, Ainurofiq A. Formulation development and in vivo study of nanoemulgel of Channa striata and Citrus limon extract for caesarean wound treatment. Acta Pharmaceutica Sciencia. 62(3).
  62. Ainurofiq A, Prasetya A, Rahayu BG, Al Qadri MS, Kovusov M, Laksono OEP. Recent Developments In Brain-Targeted Drug Delivery Systems via Intranasal Route. Farmacja Polska. 2023;78(12):695-708.
  63. Ainurofiq A, Rahayu BG, Murtadla FA, Kuncahyo I, Windarsih A, Choiri S. QbD-based formulation development of resveratrol nanocrystal incorporated into soluble mesoporous material: Pharmacokinetic proof of concept study. International Journal of Pharmaceutics. 2024;661:124459.
  64. Lombardo R, Ruponen M, Rautio J, et Development of Lyophilised Eudragit® Retard Nanoparticles for the Sustained Release of Clozapine via Intranasal Administration. Pharmaceutics. 2023;15(5):1554.
  65. Ainurofiq A, Daryati A, Murtadla FA, Salimah F, Akbar NM, Faizun RA. The Use of Natural and Synthetic Polymers in the Formulation of Gastro retentive Drug Delivery System. International Journal of Drug Delivery Technology. 2023;13(01):434-441.
  66. Bahadur S, Jha MK. Emerging nanoformulations for drug targeting to brain through intranasal delivery: A comprehensive review. Journal of Drug Delivery Science and Technology. 2022;78:103932.
  67. Ghadiri M, Young P, Traini D. Strategies to Enhance Drug Absorption via Nasal and Pulmonary Routes. Pharmaceutics. 2019;11(3):113.
  68. Miller JL, Ashford JW, Archer SM, Rudy AC, Wermeling DP. Comparison of Intranasal Administration of Haloperidol with Intravenous and Intramuscular Administration: A Pilot Pharmacokinetic Study. Pharmacotherapy. 2008;28(7):875-882.
  69. Shah V, Sharma M, Pandya R, et al. Quality by Design approach for an in situ gelling microemulsion of Lorazepam via intranasal route. Materials Science and Engineering: C. 2017;75:1231-1241.
  70. Abdou EM, Kandil SM, Miniawy HMFE. Brain targeting efficiency of antimigrain drug loaded mucoadhesive intranasal nanoemulsion. International Journal of Pharmaceutics. 2017;529(1-2):667-677.